Content uploaded by Wendy Saltzman
Author content
All content in this area was uploaded by Wendy Saltzman on Nov 14, 2017
Content may be subject to copyright.
This page intentionally left blank
Chapter 13
Hormones and Reproductive
Cycles in Primates
Wendy Saltzman*, Suzette D. Tardif
y
and Julienne N. Rutherford**
*
University of California, Riverside, CA, USA,
y
University of Texas, San Antonio, TX, USA,
**
University of Illinois at Chicago, Chicago, IL, USA
SUMMARY
Primates are characterized by long lifespans, slow reproductive
processes, and low fecundity. Gonadarche is a late and prolonged
process in which the maturation of the hypothal-
amicepituitaryegonadal (HPG) axis is followed by a period of
‘adolescent infertility’. Ovarian cycles are prolonged, with spon-
taneous ovulation of one ovum (or several ova, in some species)
followed by a spontaneous luteal phase supporting development of
the uterine endometrium. Following conception, in the anthropoid
primates (monkeys, apes, and humans) an invasive hemochorial
placenta supports a prolonged gestation and offers the opportunity
for placental endocrine signals to be transmitted directly to the
maternal blood. Mothers produce dilute milk over long periods,
supporting slow postnatal growth rates. Lactation induces anov-
ulation in most primates through a process linked to the suckling
stimulus. Seasonal, energetic, and social factors can all influence
the course of puberty, conception, pregnancy, and, to a lesser
extent, lactation. Primates experience a long reproductive life,
typically with age-related reductions in female fertility and in
male androgen production. As much as 25% of the female’s
maximal lifespan may be postreproductive, with reproductive
senescence driven primarily by loss of the follicular pool.
1. OVERVIEW OF THE PRIMATES
The order Primates includes roughly 230 extant species in
two suborders: the Strepsirhini, comprising the lemurs, lor-
ises, galagos, and pottos (also referred to as prosimians,
along with tarsiers); and the Haplorhini, comprising the
tarsiers, Platyrrhini (New World monkeys), Cercopithecoi-
dea (Old World monkeys), Hylobatidae (lesser apes; i.e.,
gibbons and siamangs), and Hominidae (humans and great
apes; i.e., orangutans, gorillas, chimpanzees, and bonobos)
(Bininda-Emonds et al., 2007; Hartwig, 2007)(Figure 13.1).
Primates exhibit tremendous diversity in body size, ranging
from the 30 to 60 g mouse lemurs (Microcebus spp.) (Yo d e r
et al., 2000) to the roughly 200 kg gorillas (Gorilla gorilla)
(Smith & Jungers, 1997), and in longevity, ranging from
approximately nine years in several prosimians to roughly 60
years in great apes and over 120 years in humans (AnAge:
The Animal Ageing and Longevity Database, 2009). They
occupy a diversity of habitats, from tropical forests to
savannas to semideserts, and exhibit a variety of lifestyles,
from arboreal to terrestrial, from diurnal to nocturnal, and
from largely dispersed and solitary to highly gregarious.
None-the-less, primates as a group are characterized by long
lifespans, delayed reproductive maturation, low fecundity,
and high investment in each offspring (Zimmermann &
Radespiel, 2007).
In this chapter, we summarize current perspectives on
and understanding of reproductive function in human
and nonhuman primates, including the hypothal-
amicepituitaryegonadal (HPG) axis function across the
lifespan; pregnancy and lactation; sexual behavior and its
hormonal underpinnings; and seasonal, social, and ener-
getic influences on reproduction. Descriptive data on
reproductive patterns are available for several hundred
primate species and subspecies studied in the wild and/or in
captivity (Zimmermann & Radespiel, 2007). In contrast,
experimental investigations of reproductive physiology
have focused largely on humans and a small number of
monkey species, especially the Old World macaques
(Macaca spp.) and baboons (Papio spp.), and the New
World squirrel monkeys (Saimiri spp.) and marmosets
(Callithrix spp.). By necessity, we focus mainly on the best-
studied taxa; however, we also attempt to highlight the
diversity among primates (Table 13.1).
2. TESTICULAR FUNCTION AND ITS
NEUROENDOCRINE CONTROL
As in other mammals, the two major functions of the tes-
tesdspermatogenesis and androgen productiondtake place
in anatomically and functionally distinct testicular
compartments. Spermatogenesis occurs within the seminif-
erous tubules, whereas androgen production occurs primarily
Hormones and Reproduction of Vertebrates, Volume 5dMammals 291
Copyright Ó2011 Elsevier Inc. All rights reserved.
in the Leydig cells of the testicular interstitium. Both
processes are controlled by the HPG axis. Therefore, we
begin by briefly reviewing this endocrine axis and its control
of androgen secretion, and then discuss spermatogenesis and
its hormonal control.
2.1. The Hypothalamicepituitaryegonad
(HPG) Axis and Androgen Secretion in Males
In both sexes, gametogenesis and gonadal steroid secretion
are ultimately regulated by gonadotropin-releasing
hormone (GnRH), a decapeptide synthesized in neuronal
cell bodies in the arcuate nucleus of the medial basal
hypothalamus and released into the hypothal-
amicehypophysial portal blood vessels in a pulsatile
manner (see Chapter 2, this volume). The cellular and
molecular mechanisms responsible for the generation of
GnRH pulses are not yet understood, but appear to involve
endogenous oscillations within the GnRH neurons them-
selves (Terasawa, 2001; Zeleznik & Pohl, 2006; see also
Chapter 2, this volume). Stimulatory inputs to the GnRH
pulse generator in primates include kisspeptin (Kp),
norepinephrine, glutamate, neuropeptide Y (NPY), and
nitric oxide, while inhibitory inputs include endogenous
opioids,
g
-aminobutyric acid (GABA), and corticotropin-
releasing hormone (CRH) (Terasawa, 2001; Zeleznik &
Pohl, 2006; Plant & Ramaswamy, 2009).
At the anterior pituitary, GnRH binds to gonadotropes
to stimulate synthesis and secretion of two glycoprotein
hormones: luteinizing hormone (LH) and follicle-stimu-
lating hormone (FSH). A notable exception to this pattern
occurs in at least some New World monkeys (common
marmoset (Callithrix jacchus), Bolivian squirrel monkey
(Saimiri boliviensis), Ma’s owl monkey (Aotus nancy-
maee)), in which the pituitary secretes chorionic gonado-
tropin (CG) instead of LH. Correspondingly, the gonads in
some or all New World monkeys express a modified form
of the LH receptor, in which exon 10 is not expressed and
which is activated selectively by CG (Gromoll et al., 2003;
Mu
¨ller et al., 2004a; 2004b; Scammell, Funkhouser,
Moyer, Gibson, & Willis, 2008).
The major function of LH in males is the stimulation of
androgen release by the Leydig cells. Correspondingly,
testosterone (T) is an important regulator of LH secretion,
exerting negative feedback to reduce the frequency of LH and
presumably GnRH pulses (reviewed by Tilbrook & Clarke,
2001). Testosterone-mediated feedback in primates is
thought to occur primarily at the level of the brain, rather than
the pituitary. The neuroanatomical substrates of this feed-
back, however, are not yet known. Gonadotropin-releasing
hormone neurons in mammals do not appear to contain
Lorisoidea
(lorises, pottos,
galagos)
Lemuroidea
(lemurs)
Tarsius
(tarsiers)
Platyrrhini
(New World monkeys)
Cercopithecoidea
(Old World monkeys)
Hylobatidae
(lesser apes)
Homo sapiens
(human)
Pan paniscus
(bonobo)
Pan troglodytes
(chimpanzee)
Gorilla gorilla
(gorilla)
Pongo pygmaeus
(orangutan)
72.8
72.8
11.7
81.7
51.0
34.4
16.6
30.7
21.4
18.0
11.5
4.5
4.5
8.6
2.9
6.5
3.4
13.0
2.8
4.1
Strepsirhini
ProsimiansHominoidea
Catarrhini
Haplorhini
Anthropoidea
Hominidae
FIGURE 13.1 Cladogram showing the major extant primate taxa, with branch lengths in millions of years. Based on Bininda-Emonds et al. (2007).
292 Hormones and Reproduction of Vertebrates
receptors for androgens, estrogens, or progesterone (P
4
);
thus, feedback by these steroids must be mediated by
other cell populations. To date, the endogenous opiates,
GABA, and Kp have all been implicated as possible
mediators of androgenic feedback on GnRH in rhesus
macaques (Macaca mulatta)(El Majdoubi, Ramaswamy,
Sahu, & Plant, 2000; Shibata, Friedman, Ramaswamy, &
Plant, 2007). Intracellular aromatization of T to estradiol
(E
2
) within the brain also has been implicated in the
feedback regulation of the HPG axis in male primates, as
in other mammals; however, studies have yielded incon-
sistent results (Tilbrook & Clarke, 2001).
In contrast to LH, the major functions of FSH in males
involve development of the gonads, especially production
of Leydig cells, and regulation of spermatogenesis, the
latter being mediated through actions on Sertoli cells (see
Section 2.2). Follicle-stimulating hormone also differs
from LH in the hypothalamic and gonadal mechanisms
regulating its secretion (Plant & Marshall, 2001). Whereas
LH release is highly sensitive to GnRH pulse frequency,
FSH release is not, so that changes in GnRH pulse
frequency alter the ratio of circulating FSH to LH (Zeleznik
& Pohl, 2006). The occurrence of a separate, selective
hypothalamic FSH-releasing factor has been postulated but
has not been confirmed, and seems unlikely to play
a significant role in primates (Zeleznik & Pohl, 2006).
Moreover, the inhibitory effects of T on FSH secretion,
apparently mediated through aromatization to E
2
, are less
pronounced than those controlling LH release. Instead, the
major testicular hormones controlling FSH secretion are
inhibin B and activins, glycoprotein hormones produced by
the Sertoli cells that inhibit and stimulate, respectively,
pituitary release of FSH (McLachlan et al., 2002b).
2.2. Spermatogenesis
Spermatogenesis comprises three major processes: mitotic
proliferation, which maintains the population of stem cell
spermatogonia and produces differentiated spermatogonia
and primary spermatocytes; meiotic division, in which
each diploid primary spermatocyte gives rise to two
secondary spermatocytes and, subsequently, to four
haploid sperm, involving development of head and tail
structures; and spermiation, or release of sperm into the
lumen of the seminiferous tubules (Johnson & Everitt,
2000; Plant & Marshall, 2001; McLachlan et al., 2002b;
see also Chapter 5, this volume) (Figure 13.2). In most
respects, these processes are similar in all mammals;
however, some noteworthy differences have been found
between primates and nonprimates as well as among
primate species.
Spermatogonia are classified as either type A (undif-
ferentiated, including stem cell spermatogonia and prolif-
erative spermatogonia) and type B (differentiated
spermatogonia). In primates, but not rodents, type A sper-
matogonia are further divided into two morphologically
distinct subtypes: A-pale, which undergo mitotic divisions
to produce new type A and type B spermatogonia, and
A-dark, which are thought to constitute a pool of reserves
that begin to proliferate only under conditions of testicular
damage (McLachlan et al., 2002b; Luetjens, Weinbauer, &
Wistuba, 2005)(Figure 13.2).
Beginning at puberty, A-pale spermatogonia, occupying
the basal compartment of the seminiferous tubules, undergo
a limited number of mitotic divisions to yield type A as well
as type B daughter cells. Subsequently, type B spermato-
gonia undergo one or more mitotic divisions to yield
primary spermatocytes. The number of mitotic divisions at
each stage differs reliably among species. The duration of
the spermatogenic cycle (i.e., the time between consecutive
spermatogonial divisions to produce spermatocytes in
a single section of seminiferous tubule) in New World and
Old World monkeys averages approximately 10 days, with
longer cycles reported in chimpanzees (Pan troglodytes)
(14.4 days) and humans (16 days) (Luetjens et al., 2005).
As in other taxa, spermatogenesis in primates is gov-
erned largely by the Sertoli cells, the only somatic cells
present in the seminiferous tubules (Sofikitis et al., 2008).
Functions of these cells include forming the bloodetestis
barrier, maintaining the cytoarchitecture of the germinal
epithelium, producing nutrients that provide energy for the
germ cells, regulating FSH secretion via secretion of
inhibins and activins, and mediating androgenic effects on
spermatogenesis through expression of androgen receptors
and production of androgen-binding protein.
In rodents, each cross section of seminiferous tubule
contains germ cells in only a single stage of spermato-
genesis. A similar pattern is found in prosimian primates.
Among great apes and humans, however, most tubular cross
sections contain germ cells in multiple stages of sper-
matogenesis. Monkeys show intermediate patterns, but the
proportion of so-called multi-stage tubules is higher in New
World than Old World monkeys (Wistuba et al., 2003). The
functional significance of these differences, if any, is not
clear. Spermatogenic efficiency, defined as the absolute
number of germ cells produced relative to the theoretical
number, does not appear to vary markedly across primate
species or to differ between species with single-stage vs.
multi-stage tubules, although efficiency is lower in
numerous primate species than in the rat (Rattus norvegi-
cus)(Luetjens et al., 2005).
In rats, FSH and T play critical roles in regulating
spermatogenesis, acting both separately and synergisti-
cally. Among primates, the relative roles of these two
hormones are less clear but differ to some extent from
those in rodents (reviewed by McLachlan et al., 2002a;
2002b; Luetjens et al., 2005; Sofikitis et al., 2008).
Follicle-stimulating hormone appears to be necessary for
293Chapter | 13 Hormones and Reproductive Cycles in Primates
TABLE 13.1 Reproductive and life-history parameters for representative primate species
Adrenarche
Age at sexual
maturityd
males (days)
Age at sexual
maturityd
females (days)
Ovarian
cycle length
(days) Menstruation
Birth
seasonality*
Female age
at first
parturition
(years)
Strepsirhini
Microcebus murinus
(gray mouse lemur)
243
1
243
1
50.5
23
Absent/covert
9
Strong
18
0.67
28
Daubentonia
madagascariensis
(aye-aye)
882
1
49.8
23
Absent/covert
9
Absent
18
3.5
28
Lemur catta (ring-tailed
lemur)
912
1
595
1
39.3
23
Absent/covert
9
Strong
18
2.13
28
Eulemur fulvus (brown
lemur)
548
1
608
1
29.5
23
Absent/covert
9
Strong
18
2.41
28
Varecia variegata (ruffed
lemur)
608
1
604
1
30
2
Absent/covert
9
Strong
4
2.0
28
Propithecus verreauxi
(Verreaux’s sifaka)
912
1
912
1
Absent/covert
9
3.5
28
Otolemur crassicaudatus
(thick-tailed greater
galago)
639
1
495
1
44.0
23
Absent/covert
9
Strong
24
2.17
28
Perodicticus potto (Western
potto)
547
1
547
1
37.9
23
Absent/covert
9
Weak
24
2.03
28
Tarsius
Tarsius bancanus (Western
tarsier)
920
1
24.0
23
Absent/covert
9
Strong
19
2.52
28
Platyrrhini
Callimico goeldii (Goeldi’s
monkey)
395
1
365
1
23.8
23
Absent/covert
23
Weak; possibly
bimodal
13
1.32
28
Callithrix jacchus (common
marmoset)
Absent
29
382
1
477
1
28.6
23
Absent/covert
9
Weak; bimodal
13
1.44
28
Callithrix pygmaea (pygmy
marmoset)
638
1
684
1
33.3
33
Absent/covert
23
Weak; bimodal
13
1.88
28
Saguinus oedpius (cotton-
top tamarin)
550
1
548
1
22.7
23
Absent/covert
23
Weak
13
1.89
28
Leontopithecus rosalia
(golden lion tamarin)
730
1
547
1
18.5
23
Absent/covert
23
Weak; sometimes
bimodal
13
2.40
28
Saimiri sciureus (common
squirrel monkey)
1,826
1
1,003
1
9.1
23
Absent/covert
9
Strong
20
2.5
28
Cebus apella (brown
capuchin)
1,703
1
20.0
23
Slight
9
Weak
20
5.64
28
Alouatta caraya (black
howler monkey)
928
1
1,167
1
20.4
23
None/weak
14
3.71
28
Lagothrix lagotricha
(Humboldt’s woolly
monkey)
1,520
1
2,555
1
25
2
Slight
9
Weak
13
6.29
28
Ateles geoffroyi (Geoffroyi’s
spider monkey)
1,826
1
1,825
1
25.5
23
Slight
9
Weak
14
6.0
28
Brachyteles arachnoides
(muriqui)
2,738
1
21.0
23
Weak
7
7.5
28
Callicebus moloch (dusky
titi)
912
1
17
12
Absent/covert
12
Weak
12
3
28
Pithecia pithecia (white-
faced saki)
1,460
1
775
1
16-17
25
Weak
25
2.08
28
Aotus trivirgatus (northern
night monkey)
730
1
821
1
15.6
23
Absent/covert
9
Weak
13
2.40
28
294 Hormones and Reproduction of Vertebrates
TABLE 13.1 Reproductive and life-history parameters for representative primate species
Gestation
length
(days)
Interbirth
interval
(months)
Modal
litter
size
Age at
weaning
(days)
Maximum
recorded
lifespan in
captivity (years)
% of lifespan
completed
at time of
last birth
z
Mean body
massdwild
adult
females (g) Placentation
Superficial,
epitheliochorial,
villous
3
60
28
3
28
2
28
40
28
18.2
1
63
28
167
28
20
28
1
28
268
28
23.3
1
2,531
28
135
28
14
28
1
28
142
28
37.3
1
76.7% (C) (Lemur
spp.)
17
2,250
28
120
28
24
28
1
28
159
28
35.5
1
2,228
28
139
28
12
28
2
28
90
28
36
1
3,407
28
140
28
12
28
1
28
180
28
30.5
1
3,285
28
135
28
12
28
2
28
135
28
22.7
1
1,110
28
195
28
12
28
1
28
150
28
26.8
1
836
28
Superficial,
epitheliochorial,
villous
3
178
28
8
28
1
2
79
28
16.3
1
109
28
Superficial,
hemochorial,
trabecular
3
153
28
9
28
1
28
68
28
22.2
1
355
28
148
28
6
28
2
28
76
28
22.8
1
61.7% (C)
17
334
28
137
28
6
28
2
28
90
28
18.6
1
101
28
168
28
7
28
2
28
50
28
26.2
1
404
28
129
28
6
28
2
28
90
28
31.6
1
48.6% (C)
17
579
28
170
28
9
28
1
28
197
28
30.2
1
90.5% (C)
17
681
28
154
28
22
28
1
28
263
28
46
1
2,361
28
187
28
11
1
1
28
325
28
32.4
1
4,606
28
224
28
24
28
1
28
411
28
32
1
6,303
28
227
28
37
28
1
28
786
28
47.1
1
7,480
28
233
28
34
28
1
28
747
28
30 (unconfirmed)
1
8,070
28
164
28
12
28
1
28
60
28
26.2
1
956
28
164
28
19
28
1
28
122
1
36
1
1,580
28
133
28
9
28
1
28
127
28
30.1
1
730
28
(Continued)
295Chapter | 13 Hormones and Reproductive Cycles in Primates
TABLE 13.1 Reproductive and life-history parameters for representative primate speciesdcont’d
Adrenarche
Age at sexual
maturityd
males (days)
Age at sexual
maturityd
females (days)
Ovarian
cycle length
(days) Menstruation
Birth
seasonality*
Female age
at first
parturition
(years)
Cercopithecoidea
Semnopithecus entellus
(Hanuman langur)
1,886
1
1,162
1
26.8
23
Overt
9
Absent/weak
6
3.66
28
Pygathrix nemaeus (red-
shanked douc langur)
1,460
1
Nasalis larvatus (proboscis
monkey)
1,460
1
Weak
22
4.5
28
Colobus guereza (guereza) 2,192
1
1,461
1
Absent
16
4.75
28
Macaca mulatta (rhesus
macaque)
Absent
29
2,007
1
1,231
1
26.6
23
Overt
9
Strong
27
3.75
28
Macaca fascicularis (long-
tailed macaque)
Absent
29
1,544
1
1,238
1
29.4
23
Overt
9
Weak
27
3.9
28
Macaca arctoides (stump-
tailed macaque)
2,099
1
1,186
1
29
2
Slight
9
Absent
27
3.84
28
Macaca fuscata (Japanese
macaque)
1,369
1
1,483
1
28
2
Overt
9
Strong
27
5.54
28
Macaca nemestrina (pig-
tailed macaque)
1,095
1
1,125
1
Slight
9
Weak
27
3.92
28
Papio anubis (olive baboon) 973
2
33.2
23
Overt
9
Absent
21
4.5
28
Papio hamadryas
(hamadryas baboon)
Absent
29
1,762
1
1,514
1
30
8
Overt
9
Weak
5
6.1
28
Mandrillus sphinx
(mandrill)
1,186
1
39.6
23
Weak
21
4
28
Theropithecus gelada
(gelada baboon)
2,190
1
1,391
1
35.5
23
Slight
9
Weak
5
4
28
Cercocebus torquatus
(white-collared
mangabey)
973
1
33
2
Slight
9
Weak
21
4.67
28
Chlorocebus aethiops
(vervet)
1,825
1
1,034
1
33
23
(median) Slight
9
Weak
15
4.88
28
Cercopithecus neglectus
(De Brazza’s monkey)
2,555
1
1,611
1
Weak
15
4.67
28
Erythrocebus patas (patas
monkey)
1,400
1
956
1
30.6
23
Overt
9
Weak
15
3
28
Miopithecus talapoin
(Angolan talapoin)
2,008
1
1,395
1
36
2
Overt
9
Weak
15
4.38
28
Hominoidea
Hylobates lar (white-
handed gibbon)
1,825
1
2,555
1
20.2
23
Overt
9
Weak
30
8.00
28
Hylobates syndactylus
(siamang)
2,190
1
2,190
1
7.09
28
Pongo pygmaeus
(orangutan)
2,555
1
2,555
1
29.6
23
Slight
9
10.65
28
Gorilla gorilla (gorilla) 4,015
1
2,829
1
31.1
23
Slight
9
Absent
11
8.1
28
Pan paniscus (bonobo) 3,194
1
42
31
Weak
10
13-15
28
296 Hormones and Reproduction of Vertebrates
TABLE 13.1 Reproductive and life-history parameters for representative primate speciesdcont’d
Gestation
length
(days)
Interbirth
interval
(months)
Modal
litter
size
Age at
weaning
(days)
Maximum
recorded
lifespan in
captivity (years)
% of lifespan
completed
at time of
last birth
z
Mean body
massdwild
adult
females (g) Placentation
Interstitial,
hemochorial, villous
3
192
28
17
28
1
28
354
28
29
1
94.1% (FP)
17
10,470
28
210
28
20
28
1
28
330
1
26
1
8,180
28
166
28
18
28
1
28
246
28
25.1
1
9,593
28
170
28
20
28
1
28
371
28
35
1
8,401
28
165
28
12
28
1
28
279
28
40
1
66.7% (C)
17
, 73.5%
(SF)
17
6,890
28
164
28
13
28
1
28
375
28
39
1
3,582
28
178
28
19
28
1
28
393
28
29.2
1
8,400
28
173
28
24
28
1
28
453
28
38.5
1
67.3% (FP)
17
8,565
28
169
28
14
28
1
28
300
28
37.6
1
69.2%(C)
17
5,657
28
180
28
25
28
1
28
592
28
25.2
28
92.6% (FP)
17
13,233
28
170
28
24
28
1
28
561
28
37.5
1
10,568
28
198
28
17
28
1
28
349
28
40
1
12,125
28
170
28
24
28
1
28
465
28
36
1
11,427
28
171
28
13
28
1
28
46
1
5,500
28
163
28
12
28
1
28
262
28
30.8
1
66.9% (C)
17
3,020
28
167
28
12
28
1
28
393
28
30.8
1
3,816
28
167
28
12
28
1
28
234
28
28.3
1
6,409
28
164
28
12
28
1
28
188
28
27.7
1
1,560
28
Interstitial,
hemochorial, villous
3
209
28
30
28
1
28
639
28
56
1
5,403
28
232
28
50
28
1
28
639
28
43
1
10,568
28
250
28
72
28
1
28
1,273
28
59
1
68.1% (C)
17
36,389
28
273
28
47
28
1
28
1,061
28
55.4
1
51.9% (C)
17
80,000
28
240
28
48
28
1
28
1,080
28
55
1
33,200
28
(Continued)
297Chapter | 13 Hormones and Reproductive Cycles in Primates
proliferation of A-pale spermatogonia, transition of A-
pale to B spermatogonia, and spermiation. T, on the other
hand, is thought to stimulate late spermatid differentia-
tion, whereas both T and FSH may play roles in sup-
pressing apoptosis in germ cells and in regulating meiotic
divisions by spermatocytes. Other hormones that have
been implicated in modulating spermatogenesis in
primates include LH, insulin, inhibin, activin, follistatin,
somatostatin, and estrogens (Sofikitis et al., 2008).
3. OVARIAN FUNCTION AND ITS
NEUROENDOCRINE CONTROL
3.1. Overview
Ovarian cycles in primates, like those in other mammals,
comprise (1) a preovulatory (follicular) phase, character-
ized by follicular maturation, increasing follicular secretion
of estrogens, and generally low circulating levels of
gonadotropins (GTHs); (2) ovulation, precipitated by
midcycle surges in estrogens and GTH secretion; and (3)
a postovulatory (luteal) phase, dominated by formation of
a corpus luteum (or, in some species, several corpora lutea)
from the ovulated follicle(s), luteal production of P
4
(and
estrogens), and low pituitary GTH levels (Figure 13.3) (see
also Chapter 4, this volume). In all primate species studied
to date, but in contrast to numerous other mammals,
follicular development, ovulation, and corpus luteum
formation occur spontaneously, independent of mating-
induced stimuli (Martin, 2007). Primates also tend to have
extended ovarian cycles as compared to other mammals,
with especially prolonged luteal phases (Johnson & Everitt,
2000). None-the-less, overall cycle length and duration of
the follicular and luteal phases differ markedly among
primates. Average cycle lengths tend to range from 30 to 50
days in prosimians, 16 to 30 days in New World monkeys,
24 to 35 days in Old World monkeys, 20 to 30 days in lesser
apes, and 25 to 50 days in great apes, including humans
(Van Horn & Eaton, 1979; Dixson, 1998; Martin, 2007;
Emery Thompson, 2009; Ziegler, Strier, & Van Belle,
2009) (Table 13.1). The New World squirrel monkeys
(Saimiri spp.), however, have a mean cycle length of seven
to twelve days, with a follicular phase of only about five
days (Dukelow, 1985).
As described below, menstruation occurs to some extent
in all or most Old World monkeys and apes, and in several
New World monkeys (Strassmann, 1996); thus, these species
may be said to have a true menstrual cycle. Other species,
most notably prosimians, may be considered to have an
estrous cycle, as they exhibit distinct cyclical changes in
sexual receptivity, with peak receptivity occurring during the
periovulatory period (see Section 8). Finally, many New
World monkeys exhibit neither menstruation nor strict
estrous cyclicity. For consistency, therefore, we refer simply
to ‘ovarian cycles’ in all female primates.
Dynamics of primate ovarian cycles, like many other as-
pects of reproductive physiology, have been characterized
TABLE 13.1 Reproductive and life-history parameters for representative primate speciesdcont’d
Adrenarche
Age at sexual
maturityd
males (days)
Age at sexual
maturityd
females (days)
Ovarian
cycle length
(days) Menstruation
Birth
seasonality*
Female age
at first
parturition
(years)
Pan troglodytes
(chimpanzee)
Present
29
2,920
1
3,376
1
37.3
23
Overt
9
Weak
26
13.6
28
Homo sapiens (human) Present
29
5,110
1
4,745
1
29.1
23
Overt
9
Weak
32
14.5
28
1
Data from: AnAge, The Animal Ageing and Longevity Database (http://genomics.senescence.info/species/).
2
Harvey et al., 1987.
3
Mossman, 1987.
4
Richard, 1987.
5
Stammbach, 1987.
6
Struhsaker, 1987.
7
Strier and Ziegler, 1994.
8
Rowe, 1996.
9
Strassmann, 1996.
10
Furuichi et al., 1998.
11
Watts, 1998.
12
Valeggia et al., 1999.
13
Di Bitetti and Janson, 2000.
14
Di Fiore and Campbell, 2007.
15
Enstam and Isbell, 2007.
16
Fashing, 2007.
17
Fedigan and Pavelka, 2007.
18
Gould and Sauther, 2007.
298 Hormones and Reproduction of Vertebrates
most thoroughly in macaques and women. Therefore, the
following review focuses primarily on data from these
species. We begin by summarizing the cyclical events
occurring in the ovary. We then describe cyclical changes in
the uterus and other tissues, and finally discuss the neuro-
endocrine control of primate ovarian cycles.
3.2. Cyclical Changes in the Ovaries
3.2.1. Folliculogenesis
As in other mammals, primate oogonial germ cells termi-
nate mitotic division and enter their first meiotic division
during prenatal development. The resulting primary
oocytes become encased in primordial follicles, each con-
sisting of a single layer of spindle-shaped granulosa cells,
and abruptly suspend meiosis at the diplotene stage of the
first meiotic prophase. Primordial follicles may remain in
this state of suspended animation for years or even decades,
until they initiate further development to the early antral
stage (Johnson & Everitt, 2000).
Development of primordial follicles into early antral
follicles involves growth of the oocyte, formation of a zona
pellucida, and growth and proliferation of granulosa cells,
followed by formation of the antral cavity and development
of the thecal cell layer. This phase of follicular develop-
ment, which is thought to last approximately 85 days in
humans (Gougein, 1986), may occur to a small extent
prepubertally (Zeleznik & Pohl, 2006). Beginning at
puberty, however, several primordial follicles resume
development each day, forming a continuous stream of
maturing follicles. Maturation to the early antral stage
appears to be independent of gonadotropic stimulation and
occurs during all phases of the ovarian cycle. Granulosa
cells from preantral and early antral follicles possess
receptors for FSH but not LH, whereas thecal cells possess
only LH receptors. These immature follicles do not secrete
significant amounts of estrogens under basal conditions but
can do so if stimulated with FSH for prolonged periods
(Zeleznik & Pohl, 2006).
Maturation of early antral follicles to the preovulatory
stage occurs exclusively during the follicular phase of the
ovarian cycle, under the control of LH and FSH, and
involves expansion of the antral cavity, secretion of
follicular fluid into the antrum, expression of LH receptors
by the granulosa cells, and follicular secretion of increasing
amounts of estrogens and inhibin B. As in other mammals,
estrogen production proceeds according to the ‘two cell,
two GTH’ model: thecal cells convert C21 steroids to C19
steroids (androstenedione and T) under the influence of LH,
and granulosa cells subsequently aromatize these andro-
gens to estrogens under the influence of FSH. Steroido-
genesis may be further modulated by several autocrine and
paracrine factors, including estrogens, androgens, insulin-
like growth factor (IGF)-II, activin, and inhibin; however,
the roles of these local factors in follicular steroidogenesis
are not well understood (Zeleznik & Pohl, 2006). Follicles
in which development to the early antral stage does not
correspond with the slight elevation in circulating GTH
levels at the beginning of the follicular phase are unable to
TABLE 13.1 Reproductive and life-history parameters for representative primate speciesdcont’d
Gestation
length
(days)
Interbirth
interval
(months)
Modal
litter
size
Age at
weaning
(days)
Maximum
recorded
lifespan in
captivity (years)
% of lifespan
completed
at time of
last birth
z
Mean body
massdwild
adult
females (g) Placentation
238
28
60
28
1
28
1,691
28
59.4
1
60.0% (C), 80.0% (FP)
17
31,850
28
269
28
36
28
1
28
830
28
122.5
1
41.7-50.0%
17
53,733
28
19
Gursky, 2007.
20
Jack, 2007.
21
Jolly, 2007.
22
Kirkpatrick, 2007.
23
Martin, 2007.
24
Nekaris and Bearder, 2007.
25
Norconk, 2007.
26
Stumpf, 2007.
27
Thierry, 2007.
28
Zimmermann and Radespiel, 2007 (if >1 value was provided for a species, the mean of all values for the species was used).
29
Nguyen and Conley, 2008.
30
Savini et al., 2008.
31
Emery Thompson, 2009.
32
Vitzthum et al., 2009.
33
Ziegler et al., 2009.
*Strong: highly predictable and relatively short breeding and birth periods; evidence of altered gonadal function in non-breeding season. Weak: breeding and birth
period peaks are seen, but births can occur in any month. Absent: limited or no evidence of breeding or birth peaks.
z
C: captive breeding colonies. FP: free-ranging and provisioned. SF: semi-free-ranging and provisioned
299Chapter | 13 Hormones and Reproductive Cycles in Primates
FIGURE 13.2 Spermatogenesis in the long-tailed macaque (Macaca fascicularis). Arrows indicate the progression of cells through spermatogonial
proliferation and differentiation, meiotic division, and spermiogenesis. Dual arrows between A-dark and A-pale spermatogonia indicate the likely
transdifferentiation between these cell types (see text for discussion). PI-Z indicates preleptotene-zygotene spermatocytes. Reproduced from McLachlan
et al. (2002a), with permission from the American Society of Andrology.
100
32
24
15
8
0
2000
1500
1000
500
00
048
12 18 20 24 28 4
10
20
30
40
IU/L
E2 pmoL/L
P nmoL/L
CYCLE DAY
0
100
200
Inhibin pg/ml
A
B
E2
P4
LH
FSH
Menses
GnRH
pulses
Menses
(b)(a)
FIGURE 13.3 (a) Schematic depiction of the hypothalamicepituitaryeovarian axis. (b) Hormonal changes across the human menstrual cycle, including
relative amplitude (depicted by length of arrows) and frequency (depicted by density of arrows) of hypothalamic gonadotropin-releasing hormone GnRH
release, and circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E
2
), progesterone (P), inhibin A, and
inhibin B. Reproduced from Randolph (2008) with permission from Wiley-Blackwell.
300 Hormones and Reproduction of Vertebrates
mature further, and undergo atresia (Johnson & Everitt,
2000).
In most primates, only one follicle ovulates in each
cycle. This ‘dominant follicle’ emerges during the mid-
follicular phase and inhibits maturation of other follicles by
secreting large amounts of estrogens and possibly inhibin
B, thereby reducing FSH concentrations below the
threshold level required for maturation of early antral
follicles. At the same time, the dominant follicle signifi-
cantly increases its own expression of FSH and LH recep-
tors and develops a markedly denser capillary network than
those supplying less mature follicles. Together, these
changes ensure continuing GTH support for the dominant
follicle, in spite of the declining FSH levels that lead to
atresia of other follicles (Zeleznik & Pohl, 2006).
3.2.2. Ovulation
At the end of the follicular phase, sustained high concen-
trations of circulating estrogens from the dominant follicle
exert positive feedback on the hypothalamus and pituitary
(see Section 3.8) to trigger surges in secretion of GnRH,
FSH, and, most dramatically, LH. Within several hours, the
LH surge stimulates the primary oocyte to complete its first
meiotic division. As in other mammals, this division is
asymmetric, with half of the chromosomes and almost all
of the cytoplasm being inherited by one daughter cell, the
secondary oocyte; the other daughter cell, or first polar
body, subsequently dies. The secondary oocyte immedi-
ately begins its second meiotic division but abruptly
becomes arrested again at metaphase (Johnson & Everitt,
2000).
The LH surge also stimulates final preovulatory matu-
ration and secretory activity of the dominant follicle,
including vascularization of the granulosa cell layer, a large
increase in the volume of follicular fluid and in follicular
size, a transient rise in secretion of estrogens and andro-
gens, and initiation of P
4
secretion. Finally, LH stimulates
increased expression of collagenase, prostaglandins,
vascular endothelial growth factor, matrix metal-
loproteinases, and their inhibitors within the follicle,
leading to rupture of the follicle and ejection of the oocyte
and its surrounding cluster of granulosa cells, the cumulus
oophorus, out of the ovary and into the oviduct (Duffy &
Stouffer, 2003; Stouffer, Xu, & Duffy, 2007).
3.2.3. Corpus luteum formation, function, and
regression
Luteinization of the dominant follicle in response to the
midcycle LH surge involves marked growth of the gran-
ulosa cells, proliferation of rough and smooth endoplasmic
reticulum, structural modifications in the mitochondria,
vascularization of the luteal cells, and increased gene
expression (Zeleznik & Pohl, 2006; Stouffer et al., 2007).
In humans and macaques, corpora lutea have an intrinsic
lifespan of 14e16 days in nonconceptive cycles. During
this time, they secrete both steroid and peptide hormones,
including P
4
, estrogens, relaxin, oxytocin (OXY), and
inhibin A, primarily under the influence of LH. Both FSH
and prolactin (PRL) have additionally been implicated as
luteotropic hormones in primates, but appear to play minor
roles in stimulating endocrine activity of corpora lutea in
normal cycles (Zeleznik & Pohl, 2006). Interestingly, in
a number of New World monkeys, atretic follicles are
converted into accessory corpora lutea or interstitial glan-
dular tissue, following luteinization of the granulosa cells
or theca interna, respectively. These structures might, in
turn, contribute to the extremely high circulating concen-
trations of estrogens and P
4
characteristic of New World
primates (Dixson, 1998).
The causes of luteal regression in primates are not well
understood. In contrast to many nonprimates, this process
does not appear to be mediated to a significant extent by
endogenous prostaglandins. Moreover, luteal regression
does not appear to be determined by the decline in LH
pulse frequency that occurs over the course of the luteal
phase. Instead, luteal cells are thought to undergo
apoptosis, associated with decreases in LH responsiveness
and steroidogenic capacity (Brannian & Stouffer, 1991;
Nakano, 1997).
3.3. Cyclical Changes in the Uterus
Anthropoid primates, along with several additional
mammalian species (e.g., Rasweiler & De Bonilla, 1992;
Zhang et al., 2007; Z. Wang, Liang, Racey, Y. Wang, &
Zhang, 2008), are unique among mammals in undergoing
a menstrual cycledi.e., a cyclical pattern of changes in the
nonpregnant uterus characterized by regular sloughing of the
endometrium. Menstruation appears to be absent in all
strepsirhines and possibly tarsiers, presumably in association
with the noninvasive form of placentation used by these
species (Martin, 2007)(seeSection 5). Among the anthro-
poid primates, menstruation occurs in some New World
monkeys and apparently in all catarrhines (Old World
monkeys, apes, and humans) (Strassmann, 1996). The func-
tional significance of menstruation is not yet understood. One
hypothesis, that it protects females against sperm-borne
pathogens (Profet, 1993), has been largely discounted
(Strassmann, 1996; Martin, 2007), and an alternative
hypothesis, that cyclical shedding and regrowth of the
endometrium is energetically less expensive than maintain-
ing the endometrium in a well-developed state across the
entire cycle (Strassmann, 1996), has not been confirmed
(Martin, 2007). Menstruation has also been suggested to be
a nonadaptive consequence of the evolution of an invasive
301Chapter | 13 Hormones and Reproductive Cycles in Primates
association between the embryo and an adaptive inflamma-
tory reaction of the endometrium (Finn, 1998).
The uterine cycle in catarrhines comprises four main
phases (Figure 13.4). The proliferative phase, correspond-
ing to the mid to late follicular phase of the ovarian cycle, is
characterized by increasing growth and vascularization of
the endometrium under the influence of estrogens. During
this time, edema and proliferation of endometrial stromal
cells cause a marked increase in endometrial thickness;
increases in size, number, and tortuosity of endometrial
glands lead to development of a glandular network; and
angiogenesis results in development of an elaborate
vasculature. In addition, E
2
induces expression of both
estrogen receptors (ERs) and P
4
receptors (PRs) in endo-
metrial cells, thereby performing an obligate priming
function for the subsequent secretory phase (Johnson &
Everitt, 2000; Hess, Nayak, & Giudice, 2006).
The secretory phase of the uterine cycle corresponds to
the luteal phase of the ovarian cycle. Under the influence of
P
4
acting in concert with E
2
, the endometrium undergoes
additional histological and biochemical changes, including
accumulation of glycogen by glandular epithelial cells;
synthesis and secretion of glycoprotein-rich fluid into the
glandular lumen; cell proliferation, increased capillary
permeability, and edema in the stroma; and coiling of the
characteristic spiral arterioles. The endometrium is recep-
tive to implantation of a blastocyst during a narrow time
window, corresponding to six to ten days after the LH surge
in women (Johnson & Everitt, 2000; Hess et al., 2006).
The menstrual phase of the nonconceptive uterine cycle
begins at the end of the luteal phase of the ovarian cycle, as
luteal regression causes a decline in circulating P
4
and E
2
concentrations. In the absence of steroid support, lysosomal
membranes in the endometrium break down, releasing lytic
enzymes that degrade cellular elements and extracellular
FIGURE 13.4 The menstrual cycle and its endocrine control in catarrhines, including cyclical changes in thickness, vascularization, glandular
development, and secretory activity of the endometrium; phases of the uterine cycle and their major cellular events; circulating concentrations of estradiol
(E
2
) (solid line) and progesterone (P) (dotted line); window of implantation (WOI); and sonograms of the endometrium during the early proliferative, late
proliferative, and secretory phases. Reproduced from Giudice (2006) with permission; originally published by BioMed Central. See color plate section.
302 Hormones and Reproduction of Vertebrates
matrix; spiral arterioles constrict, causing ischemia and
vascular injury; plasminogen activators are released from
the vascular endothelium, leading to production of plasmin
and inhibition of clotting; and endometrial cells undergo
apoptosis. Whereas the endometrium is resorbed in other
mammals, in anthropoid primates the innermost two thirds
of the endometrial lining and blood from the ruptured
arterioles are expelled through the cervix and vagina as
menstrual discharge (Lockwood, Krikun, Hausknecht,
Want, & Schatz, 1997; Bergeron, 2000; Hess et al., 2006).
By convention, the first day of menstruation is designated
day one of a new cycle, corresponding to the beginning of
the follicular phase.
Finally, menstruation is followed by a postmenstrual
repair phase lasting several days in the early to mid
follicular phase of the ovarian cycle. During this time, the
endometrium heals and begins to regenerate its epithelial,
stromal, and vascular components. These processes appear
to be estrogen-independent and are thought to be initiated
by a small population of endometrial stem cells (Bergeron,
2000; Hess et al., 2006).
3.4. Cyclical Changes in the Oviducts
In primates and other mammals, the oviducts undergo
cyclical changes in histology, secretory function, and
muscular activity under the influence of ovarian steroid
hormones. During the follicular phase of the ovarian cycle,
E
2
stimulates proliferation, hypertrophy and ciliation of
epithelial cells, especially in the fimbrial and ampullary
portions of the oviducts, as well as secretion of oviductal
fluid and spontaneous muscle contractions. These changes
peak during the periovulatory period and wane during the
luteal phase, when the oviductal epithelial cells undergo
atrophy, deciliation, and apoptosis under the influence of
P
4
, and secretion of oviductal fluid declines. This cyclical
series of events is thought to play important roles in facil-
itating sperm transport, fertilization, early development of
the conceptus, and implantation (Johnson & Everitt, 2000;
Hess et al., 2006).
3.5. Cyclical Changes in the Cervix
The primate cervix undergoes cyclic, steroid-dependent
fluctuations in muscular and secretory activity (reviewed by
Johnson & Everitt, 2000; Nasir-ud-Din, Rungger-Bra
¨ndle,
Hussain, & Walker-Nasir, 2003; Suarez & Pacey, 2006).
During the follicular phase, estrogens stimulate relaxation
of the cervical muscles and increased secretion of mucus by
the cervical epithelium. Cervical mucus, which contains
water, glycoproteins, ions, enzymes, and immunoglobulins,
plays key roles in sperm transport and defense of the female
reproductive tract against microorganisms. Under the
influence of estrogens, the mucus becomes profuse, highly
hydrated, and highly penetrable to sperm. These charac-
teristics peak around the time of ovulation, when cervical
mucus blocks passage by microbes and abnormal sperm,
while guiding normal, motile sperm through the cervix.
Subsequently, during the luteal phase, P
4
increases the
firmness of the cervix, decreases secretory activity of the
cervical epithelium, and alters the quality and quantity of
glycoproteins in the cervical mucus, causing secretion of
small amounts of thick, viscous mucus that is impenetrable
to sperm.
3.6. Cyclical Changes in the Vagina
Primates, like other mammals, undergo cyclical changes in
the vagina under the influence of fluctuating estrogen and
P
4
concentrations. During the follicular phase, estrogens
stimulate increases in mitotic activity, glycogen content,
thickness, and keratinization of the vaginal columnar
epithelium, with these changes subsiding during the luteal
phase (Farage & Maibach, 2000; Poonia et al., 2006).
Cyclical changes also occur in the vaginal flora. Although
the dominant microorganisms, Lactobacillus spp., may
remain relatively constant across the menstrual cycle,
levels of other microorganisms may fluctuate (Skangalis,
Swenson, Mahoney, & O’Leary, 1979; Witkin, Linhares, &
Giraldo, 2007). Cyclical changes in the vagina are espe-
cially pronounced in prosimians. In many of these species,
as in numerous nonprimates, the vaginal orifice is imper-
forate throughout most of the cycle, openingdand there-
fore permitting intromissiondonly during the
periovulatory period (e.g., ruffed lemur (Varecia varie-
gata), Garnett’s greater galago (Otolemur garnettii), fat-
tailed dwarf lemur (Cheirogaleus medius)) (Van Horn &
Eaton, 1979; Dixson, 1998).
3.7. Cyclical Changes in the External
Genitalia and Sexual Skin
Females of many primate species undergo cyclical changes
in coloration and tumescence of the external genitalia and
so-called sexual skin, usually found on the rump and ano-
genital region (reviewed by Dixson, 1983; 1998). In
numerous prosimians, the vulva becomes swollen and
assumes a pink or red coloration during the periovulatory
period. Such changes are greatly exaggerated in many
catarrhines but are virtually nonexistent in New World
monkeys.
Typically in catarrhines, estrogens stimulate tumes-
cencedcaused largely by edemadand intensification of
the characteristic pink or red coloration of the sexual
skinda consequence of specialized vasculaturedduring
the follicular phase (Dixson, 1983). Swelling and colora-
tion peak during the periovulatory period, corresponding
with the female’s peak in sexual behavior. Progesterone
303Chapter | 13 Hormones and Reproductive Cycles in Primates
antagonizes these effects during the luteal phase, so that
detumescence occurs shortly after ovulation. Although
hormonal control appears to be consistent across species,
the location of sexual skin and extent of tumescence and
coloration vary considerably. In geladas (Theropithecus
gelada), e.g., pink or purple, nonedematous sexual skin is
found on the circumanal, paracallosal, vulval, and clitoral
regions, as well as on the lower abdomen. Additionally,
white, fluid-filled vesicles develop around the edges of the
sexual skin and in a figure-eight pattern on the chest during
the periovulatory period (Dunbar, 1977; Dixson, 1998).
Other species, including chimpanzees, bonobos (Pan pan-
iscus), baboons, red colobus (Piliocolobus badius), and
mangabeys (Cercocebus spp.), exhibit prominent pink
swellings of the circumanal, vulval, and clitoral regions.
Sex skin tumescence and coloration increase females’
attractiveness to males, may facilitate intromission by
males, and are thought to have evolved in response to
sexual selection (Dixson, 1983; 1998).
3.8. Neuroendocrine Control of the Ovarian
Cycle
The ovarian cycle in primates, as in other species, is gov-
erned by a complex interplay between the gonads, the
gonadotropes in the anterior pituitary, and the GnRH pulse
generator in the medial basal hypothalamus (reviewed by
Johnson & Everitt, 2000; Messinis, 2006; Zeleznik & Pohl,
2006; see also Chapter 2, this volume). During the follic-
ular phase, LH and FSH are released in low-amplitude,
circhoral pulses, reflecting negative-feedback effects of
estrogens on pulse amplitude but not frequency (see
Figure 13.3). At midcycle, when estrogen levels exceed
approximately 200 pg/ml for about 48 hours, estrogens
trigger positive-feedback surges in GnRH, LH, and FSH,
eliciting increases in pulse frequency and/or amplitude.
Fully developed GTH surges in women require the pres-
ence of small amounts of P
4
; however, no such effect is seen
in rhesus macaques (Zeleznik & Pohl, 2006). Finally, the
luteal phase is characterized by low-frequency, high-
amplitude LH pulses, reflecting negative feedback
primarily by P
4
. In addition to ovarian steroids, inhibin B is
secreted by the granulosa cells during the follicular phase,
and inhibin A is secreted by the corpus luteum during the
luteal phase, possibly exerting negative feedback specifi-
cally on FSH release; however, the precise role of inhibins
in primate ovarian cycles is not yet clear (Zeleznik & Pohl,
2006; Randolph, 2008). Interestingly, FSH concentrations
are elevated during the luteal phase in squirrel monkeys,
suggesting that development of antral follicles may occur
during this period, and possibly permitting the extremely
short (~five-day) follicular phase of these species (Yeoman
et al., 2000).
The sites of positive and negative feedback by estro-
gens have not been delineated fully in primates (reviewed
by Johnson & Everitt, 2000; Messinis, 2006). A variety of
experimental approaches have suggested that positive
feedback by estrogens at the pituitary alone is sufficient to
generate preovulatory LH surges, although GnRH plays an
obligate permissive role. None-the-less, other studies have
indicated that hypothalamic release of GnRH increases in
response to sustained elevations of estrogens. Negative
feedback by estrogens, likewise, may be mediated
primarily at the level of the pituitary; however, estrogens
reduce pulse amplitude (but not pulse frequency) of GnRH
as well as LH, indicating that the negative feedback effects
of estrogens are mediated in part at the hypothalamus
(Mizuno & Terasawa, 2005; see also Chapter 2, this
volume). Negative feedback effects of P
4
on GTH pulse
frequency are assumed to occur at least partly within the
central nervous system and are mediated, at least in part,
by endogenous opioids. In addition, negative feedback
effects of both estrogens and P
4
at the level of the brain
appear to be mediated in part by Kp (Plant & Ramaswamy,
2009).
4. PUBERTY
In comparison to many other taxa, primates undergo an
extended period of prepubertal development, as well as
a prolongation of the period of reproductive maturation,
known as puberty (see Table 13.1). This period is charac-
terized by morphological, physiological, and behavioral
changes driven by maturation and activation of the HPG
axis (i.e., gonadarche) and, in some species, of the hypo-
thalamusepituitaryeadrenal (HPA) axis (i.e., adrenarche).
An excellent review of puberty in primates can be found in
Plant and Witchel (2006).
4.1. Adrenarche
Several years prior to gonadarche, humans, chimpanzees,
and possibly some other catarrhines undergo remodeling of
the adrenal cortices, involving development of the zona
reticularis (i.e., the innermost zone of the adrenal cortex)
and increased secretion by the zona reticularis of andro-
gens, particularly the weakly androgenic steroids dehy-
droepiandrosterone (DHEA) and its sulfoconjugate,
DHEA-sulfate (DHEA-S). Circulating DHEA and DHEA-S
levels peak during early adulthood in both males and
females before declining gradually across the remaining
lifespan. In other primates, the development of the zona
reticularis and onset of adrenal androgen secretion occur
during the prenatal and/or early postnatal period or not at
all, and DHEA/DHEA-S secretion declines from high
levels in infancy or remains stable throughout life (Camp-
bell, 2006; Nguyen & Conley, 2008).
304 Hormones and Reproduction of Vertebrates
In humans and possibly chimpanzees, the pubertal
development of the zona reticularis, known as adrenarche,
is not associated with changes in secretion of cortisol,
corticotropin (ACTH), gonadal steroids, or GTHs, and is
not necessary for subsequent reproductive maturation
(Auchus & Rainey, 2004; Campbell, 2006). In fact, the only
known manifestations of adrenarche in humans are growth
of pubic and axillary hair; development of apocrine glands
in the skin, which may lead to body odor; and stimulation
of sebaceous gland activity, which may cause acne (Auchus
& Rainey, 2004). In addition, however, adrenarche has been
hypothesized to play a role in maturation of the brain and
skeletal system (Havelock, Auchus, & Rainey, 2004;
Campbell, 2006), and premature (precocious) adrenarche
in girls is associated with subsequent development of
several clinical disorders, including polycystic ovary
syndrome (PCOS) and metabolic syndrome (Auchus &
Rainey, 2004; Nebesio & Eugster, 2007; Belgorosky,
Baquedano, Guercio, & Rivarola, 2008).
4.2. Gonadarche
In infant primates, the pituitary and gonads secrete high
levels of GTHs (i.e., LH and FSH) and steroid hormones
(e.g., T, dihydrotestosterone (DHT), estrone (E
1
), and E
2
),
respectively, for a period of weeks to months. This period
of neonatal gonadal activity ends with the onset of the so-
called juvenile or prepubertal hiatus, during which GTH
levels drop precipitously and the gonads enter a dormant
state, especially in males (reviewed by Plant & Witchel,
2006). Gonadal ‘reawakening’ occurs at the time of
gonadarche, which begins anywhere from less than one
year of age in several prosimians (e.g., fat-tailed dwarf
lemur (C. medius)(Foerg, 1982)) to three years of age in
macaques and squirrel monkeys, to seven to eleven years
of age in chimpanzees, to nine to thirteen years of age in
humans (Dixson, 1998; Plant & Witchel, 2006).
Gonadarche in male primates is characterized by
dramatic elevations in circulating concentrations of LH
and, to a lesser extent, FSH, reflecting primarily an increase
in secretory pulse amplitude. These GTH increases, which
are thought to reflect a concomitant amplification of
pulsatile GnRH release from the hypothalamus, stimulate
an increase in testicular volume (associated with growth of
the seminiferous tubules, maturation of Sertoli cells, and
proliferation of germ cells), development of Leydig cells,
secretion of high levels of gonadal androgens, and initiation
of spermatogenesis (Plant & Witchel, 2006). In humans and
rhesus macaques, nocturnal elevations (known to be sleep-
related in boys) in circulating LH and T levels precede
diurnal elevations. The increased gonadal steroid concen-
trations stimulate development of species-typical
secondary sexual characteristics, such as sex-specific facial
and genital coloration (e.g., mandrill (Mandrillus sphinx)),
throat sac and cheek flanges (orangutan (Pongo pyg-
maeus)),and specialized facial or body hair (e.g., hama-
dryas baboon (Papio hamadryas)), as well as the onset of
sexual behavior (Dixson, 1998).
In female primates, as in males, gonadarche is triggered
by a marked increase in secretion of FSH and, especially,
LH by the gonadotropes, secondary to an increase in
hypothalamic GnRH secretion (Watanabe & Terasawa,
1989). The surge in GTHs stimulates the initiation of cyclic
ovarian activity, including the first development of Graafian
(preovulatory) follicles, increased ovarian steroidogenesis,
and, in catarrhines and some platyrrhines, the first
menstrual period (menarche) (Plant & Witchel, 2006).
Following menarche, the pituitary gonadotropes develop
the capacity to exhibit GTH release via positive feedback in
response to estrogens, culminating in the first ovulation.
Thus, menarche precedesdby approximately a year in
rhesus macaques, and by a year or more in humans and
great apesdthe onset of fertile ovulatory cycles, and is
typically associated with a period of ‘adolescent infertility,’
characterized by anovulatory and irregular cycles (Berco-
vitch & Goy, 1990; Dixson, 1998). Across puberty,
increasing E
2
concentrations stimulate uterine growth and
maturation of species-typical secondary sexual character-
istics, such as development of the breasts and nipples, and
coloration and swelling of sexual skin (Dixson, 1998).
4.3. Neural Control of Gonadarche
Human clinical cases and studies of nonhuman primates
have demonstrated that the ‘reawakening’ of the gonads at
gonadarche is not limited by maturation of the gonads,
pituitary, or hypothalamic GnRH neurons. For example,
treatment of juvenile rhesus macaques with N-methyl-D-
aspartate (NMDA), a receptor agonist of the excitatory
neurotransmitter glutamate, elicits pulsatile release of
GnRH from the hypothalamus, pulsatile release of LH from
the pituitary, and gonadal activation, indicating that the
GnRH neurons, gonadotropes, and gonads are already
mature and capable of adult-like functioning prior to
gonadarche (Plant, Gay, Marshall, & Arslan, 1989; Clay-
pool, Kasuya, Saitoh, Marzban, & Terasawa, 2000).
Further, developmental changes in neural or pituitary
sensitivity to negative feedback by gonadal steroids (the so-
called gonadostat hypothesis) do not account for the
dramatic rise in GTH release during gonadarche. Instead,
the proximate trigger for gonadarche involves maturation
of neural inputs to the GnRH neurons, eliciting the
dramatic increase in pulsatile GnRH secretion and, conse-
quently, increases in pituitary secretion of GTHs and
stimulation of gonadal endocrine and gametogenic activity.
Studies in rhesus macaques have implicated several
neurotransmitters and neuropeptides in the onset of gona-
darche. These include the inhibitory neurotransmitter
305Chapter | 13 Hormones and Reproductive Cycles in Primates
GABA, which plays a key role in restraining GnRH
secretion during the juvenile period but exerts only modest
inhibitory effects on GnRH release after the onset of
puberty (Terasawa, 2005). Moreover, the developmental
decrease in GABA release within the pituitary stalk-median
eminence may stimulate a corresponding increase in
release of the excitatory neurotransmitter glutamate, which
may further elevate GnRH secretion (Terasawa, 2005).
Neuropeptide Y has been implicated both in inhibiting
GnRH release during the prepubertal hiatus and, paradox-
ically, in stimulating GnRH release during puberty and
adulthood (Plant & Witchel, 2006).
In the past few years, much attention has focused on the
role of the neuropeptide Kp, coded for by the KiSS1 gene,
and its receptor, GPR54 (also known as KiSS1R), in
regulating gonadarche in humans and other primates (Plant
& Ramaswamy 2009). In 2003, two research groups
reported that members of consanguineous human families
presenting with hypogonadotropic hypogonadism (i.e.,
impaired gonadal function secondary to GTH deficiency)
and absence of puberty had homozygous mutations in the
GPR54 gene (De Roux et al., 2003; Seminara et al., 2003).
Since then, Kp-GPR54 signaling has been implicated
compellingly in the control of hypothalamic GnRH release,
pituitary GTH release, and onset of puberty in a number of
mammalian species, including rhesus macaques (Roa,
Aguilar, Dieguez, Pinilla, & Tena-Sempere, 2008). In
macaques, both Kp and GPR54 are expressed in the arcuate
nucleus of the medial basal hypothalamus (the site of the
GnRH pulse generator), and expression of Kp (and of
GPR54, at least in females) increases dramatically at the
time of the pubertal increase in GnRH secretion (Plant,
2009). Moreover, pulsatile release of Kp and of GnRH in
the median eminence is synchronized in midpubertal
female rhesus macaques (Keen, Wegner, Bloom, Ghatei, &
Terasawa, 2008), and treatment with exogenous Kp stim-
ulates GnRH release in midpubertal females and pulsatile
LH release in castrated juvenile males (Plant et al., 2006;
Keen et al., 2008). Importantly, the stimulatory effect of Kp
on LH can be blocked by simultaneous treatment with
a GnRH receptor antagonist, suggesting that Kp affects the
gonadotropes only indirectly, through its effects on GnRH
secretion (Plant et al., 2006). Collectively, findings from
humans and macaques suggest that Kp plays a critical role
in triggering the pubertal increase in GnRH secretion;
however, the precise nature of this role is not yet known.
4.4. Timing of Puberty
In spite of recent major advances in our understanding of
the neurobiological processes governing primate puberty,
the factors that determine the timing of these processes
remain poorly understood (reviewed by Plant & Witchel,
2006). Clearly, the determinants of the timing of puberty
are multifactorial, involving genetic, physiological, and
environmental influences. Genetic factors are estimated to
account for 50e80% of the variation in pubertal timing in
humans, with mutations in such genes as those coding for
the GnRH receptor, GPR54, and leptin leading to patho-
logically delayed or premature gonadarche; however, the
specific genes accounting for variation in pubertal timing
among clinically normal individuals remain unknown
(Gajdos, Hirschhorn, & Palmert, 2009).
At the physiological level, one hypothesis is that the
timing of puberty is governed by an endogenous ‘pubertal
clock’ in the central nervous system, which initiates
puberty at a specific age. This hypothesis is not widely
accepted, however, in view of such findings as high vari-
ability in the age of human gonadarche, both within and
among populations, as well as declines in the age of human
gonadarche over recent decades (Ebling, 2005; Plant &
Witchel, 2006; Euling, Selevan, Hirsch Pescovitz, &
Skakkebaek, 2008).
Instead, the timing of puberty has long been thought to
be governed by a putative ‘somatometer’ that measures
some index of somatic growth. The somatometer
hypothesis is supported by compelling evidence; however,
the index of somatic development being monitored is not
yet known. In recent years, attention has focused on
a possible role of the adipocyte hormone leptin, circulating
concentrations of which correlate with body fat mass.
Findings in humans and rhesus macaques, as well as
rodents, suggest that leptin plays a critical role in the onset
of gonadarche. This role appears to be permissive,
however, rather than serving as a direct trigger for puberty
onset (Ebling, 2005; Plant & Witchel, 2006; Kaplowitz,
2008). Other indices of somatic development that have
been implicated in determining the timing of puberty
include insulin, growth hormone (GH), ghrelin, and
metabolic fuels (Plant & Witchel, 2006; Kaplowitz, 2008;
Tena-Sempere, 2008). Strenuous exercise, undernutrition,
and chronic disease can all delay the onset of puberty,
possibly acting through the putative somatometer (Plant &
Witchel, 2006).
Finally, a number of environmental factors are known to
modulate the timing of puberty in humans and nonhuman
primates. Social influences can advance or delay puberty, as
described in Section 9.2. In seasonally breeding species,
aspects of pubertal maturation may be gated by seasonal
cues such as photoperiod. Female rhesus macaques housed
outdoors in the northern hemisphere, e.g., may undergo
menarche at any time of year, but the occurrence of first
ovulation is more or less restricted to the roughly three-
month breeding season (autumnewinter) and is influenced
by patterns of melatonin (MEL) secretion (Bercovitch &
Goy, 1990; Wilson, Gordon, & Collins, 1986; Wilson &
Gordon, 1989a; 1989b). Similarly, in squirrel monkeys, the
onset of ovulatory cyclicity in young females and the first T
306 Hormones and Reproduction of Vertebrates
surge in young males are restricted to the breeding season,
presumably in response to photoperiodic cues (Coe, Chen,
Lowe, Davidson, & Levine, 1981). Thus, seasonality
‘imposes a quantum effect’ on pubertal timing, such that
gonadarche is more closely dependent on the number of
breeding seasons elapsed since an individual’s birth than on
age per se (Plant & Witchel, 2006). Importantly, seasonally
related cues do not necessarily govern maturation of the
neural processes underlying pubertal reactivation of the
GnRH neurons, but instead may play a permissive role in
the expression of gonadarche, following this reactivation
(Plant & Witchel, 2006).
Recently, endocrine-disrupting chemicals have gained
attention as another source of variation in pubertal timing
(Wang, Needham, & Barr, 2005; Cesario & Hughes, 2007;
Euling et al., 2008; Schoeters, Den Hond, Dhooge, Van
Larebeke, & Leijs, 2008; see also Chapter 14, this
volume). In humans, pre- and/or postnatal exposure to
a number of synthetic or naturally occurring chemicals can
advance or delay the timing of gonadarche. For example,
correlational findings suggest that puberty in girls may be
advanced by in-utero exposure to the organochlorine
dichlorodiphenyldichloroethylene (DDE) (a metabolite of
the pesticide dichlorodiphenyltrichloroethane (DDT)), or
by exposure to phthalates, a group of estrogenic
compounds used to increase the flexibility of plastics
(Cesario & Hughes, 2007). On the other hand, puberty in
boys may be delayed by exposure to polychlorinated
biphenyls (PCBs), industrial chemicals previously used in
such products as coolants, flame retardants, and electronic
components (Schoeter et al., 2008). Exposure to exoge-
nous, naturally occurring steroids, such as phytoestrogens
found in soy products and estrogens used in certain
cosmetics and hair-care products, have additionally been
implicated in altering the timing of gonadarche (Cesario &
Hughes, 2007).
5. PREGNANCY
5.1. Overview
Numerous authors have reviewed the physiology of
mammalian pregnancy (Albrecht & Pepe, 1990; Ogren &
Talamantes, 1994; Solomon, 1994; Petraglia, Florio, &
Simoncini, 1996; Albrecht & Pepe, 1999; see also Chapter
6, this volume). Much of this literature centers upon the
best-studied primate species, i.e., humans, and is therefore
relevant background to understanding primate pregnancy.
In the following discussion, it can be assumed that findings
for nonhuman primates are similar to those found for
humans, unless otherwise stated.
Pregnancy presents unique physiological, immunolog-
ical, and evolutionary challenges due to the combined
presence of two or more distinct individuals (mother and
fetus(es)) who are inextricably linked. The interface of this
exchange between mother and fetus is the temporary organ,
the placenta. This review will concentrate on the nature of
the primate placenta, emphasizing recent findings on its
endocrine nature.
The placenta develops from the outer cell mass, or
trophectoderm, of the developing blastocyst that is in direct
contact with the maternal endometrium. The outer cell
mass eventually differentiates into two cell types: cyto-
trophoblasts and syncytiotrophoblasts. These cells form the
fetal side of the boundary between mother and fetus. This
boundary actively controls maternalefetal exchange of
nutrients, oxygen, and fetal wastes through alterations in
passive diffusion capacity and active transport capacity.
The development, maintenance, and alterations in the
placenta as an exchange surface are controlled by autocrine
and endocrine signals produced and received by the
placenta.
The form of placentation varies greatly among
mammalian taxa (Mossman, 1987; Benirschke, 2010). In
the hominoid primates (apes and humans), the entire
blastocyst implants into the uterine wall in a relatively
invasive process that involves penetration of the maternal
endometrial epithelium and invasion of the uterine vascu-
lature (Luckett, 1974; Mossman, 1987; Lee & DeMayo,
2004). Monkeys exhibit superficial implantation, in which
there is adherence to the uterine wall by the trophoblast, but
without complete endometrial penetration or invasion of
the deeper layers of the uterine wall (Luckett, 1974),
whereas humans have a more invasive interstitial implan-
tation with complete remodeling of uterine vessels. In all
anthropoid primate placentae, however, the fetal tropho-
blast layer (the chorion) is in direct contact with the
maternal blood supply; i.e., hemochorial placentation. It
has long been proposed that this most invasive form of
placentation evolved from the more shallow, epi-
theliochorial forms of placentation, but studies based on
recent phylogenetic analysis suggest that hemochorial
placentation was likely the ancestral form in mammals
(Wildman et al., 2006). Hemochorial placentation offers
the opportunity for endocrine signals produced by the
conceptusdi.e., by the cytotrophoblast and syncytio-
trophoblast cellsdto be directly transmitted to the maternal
bloodstream, offering a means for the placenta to affect
maternal physiology in ways that may either increase or
decrease fetal and placental growth (Haig, 1996; Ruth-
erford, 2009). What follows is a description of aspects of
autocrine and endocrine signaling in the primate placenta,
with an emphasis on those areas that are unusual or unique
to this taxonomic group. For broader characterization of the
dozens of endocrine/autocrine placental processes that have
been identified to date, consult Solomon (1994), Ogren and
Talamantes (1994), Petraglia et al. (1996), and Petraglia,
Floriom, and Vale (2005).
307Chapter | 13 Hormones and Reproductive Cycles in Primates
5.2. Steroids
The primate placenta interacts in a complex fashion with
the maternal and fetal blood supplies to synthesize E
2
and
P
4
and to convert cortisol to cortisone. As in other
mammals, P
4
acts to alter the endometrial environment to
allow implantation, including effects upon the maternal
immune system. Progesterone also decreases contractility
of the myometrium and inhibits lactation. Estrogens, too,
prepare the uterus for implantation, but also play a critical
role in the development of the endocrine/autocrine capac-
ities of the placenta.
Albrecht and Pepe (1999) have proposed that placental
estrogens are critical to the functional differentiation of
the primate cytotrophoblasts into a syncytiotrophoblast.
This differentiation includes an upregulation of 11
b
-
hydroxysteroid dehydrogenase (11
b
-HSD) and P450
cholesterol side-chain cleavage (P450
scc
); therefore, this
differentiation controls the ability of the placenta to
synthesize P
4
and to convert cortisol to cortisone (see
Figure 13.5).
In primates, placental estrogen synthesis is dependent
upon precursors supplied by the fetal adrenal gland. The
primate fetal adrenal gland contains a wide inner zone,
termed the fetal adrenal zone. This zone involutes rapidly
after birth in humans while in rhesus monkeys it disappears
more slowly (McNulty, Novy, & Walsh, 1981), but in all
primates it disappears before adulthood. The fetal adrenal
zone synthesizes DHEA-S, which is then used by the
syncytiotrophoblast as substrate for E
2
synthesis.
At the same time, maturation of the glucocorticoid-
producing zones of the fetal adrenal is controlled by fetal
exposure to cortisol through the placenta. In midgestation,
maternal cortisol is largely passed through the placenta as
cortisol and, therefore, inhibits the fetal pituitary’s
production of ACTH. In late gestation, with more estrogens
and, therefore, more 11
b
-HSD activity, maternal cortisol is
converted to cortisone in the placenta, reducing fetal
exposure to maternal cortisol and therefore allowing fetal
ACTH production to increase. Increased fetal ACTH
production leads to maturation of the fetal adrenal capacity
to synthesize cortisol (Pepe & Albrecht, 1990; Mesiano &
Jaffe, 1997). In this fashion, the placenta supports a time-
line of fetal development that is controlled by the pace of
developing placental endocrine/autocrine capacity.
5.3. Chorionic Gonadotropin (CG)
The syncytiotrophoblast synthesizes CG, a glycoprotein
similar to LH synthesized by the pituitary gland. For details
on the biochemistry of CG and its relation to LH and other
glycoproteins, see Ogren and Talamantes (1994). Chorionic
gonadotropin produced by the primate placenta functions to
maintain P
4
and estrogen synthesis by the corpus luteum of
the ovary. Therefore, CG is necessary for the early estab-
lishment of pregnancy in primates. In most other mammals,
maintenance of corpus luteum P
4
production is accom-
plished through embryonic effects on prostaglandin F
2a
(PGF
2a
), the primary signal for luteolysis (Niswender &
Nett, 1994). In primates and a few other species (e.g.,
guinea pigs (Cavia porcellus)), however, CG acts trophi-
cally on the ovary, in the face of waning pituitary LH
stimulation, to generate continued steroid production by the
FIGURE 13.5 Control of functional differentiation of placental syncytiotrophoblast by estrodiol (E
2
), which upregulates key components of the
progesterone (P
4
) biosynthetic pathway and the 11
b
-HSD (hydroxysteroid dehydrogenase)-1 and -2 system, which induces maturation of the fetal
pituitaryeadrenal axis. Syncytiotrophoblast is a multinucleated tissue of the placenta that produces hormones, depicted here as a drawn circle filled with
smaller circles. Quotation marks signify functionally differentiated syncytiotrophoblast that is secreting hormones; e.g., placental lactogen and P
4
.F,
cortisol; E, cortisone; DHEA, dehydroepiandrosterone. Reproduced from Albrecht and Pepe (1999) with permission.
308 Hormones and Reproduction of Vertebrates
corpus luteum (Zeleznik & Benyo, 1994). Recent studies
indicate that CG may also play a direct role in altering the
character of the endometrium in preparation for
implantation.
Numerous endocrine and autocrine factors have been
found to affect CG production in vitro, including cortisol,
CRH, triiodothyronine (T
3
), thyroxine (T
4
), GnRH, inter-
leukin 6 (IL-6), and IGF-1, which increase CG secretion,
and P
4
and transforming growth factor-
b
(TGF
b
), which
decrease CG secretion (summarized in Ogren & Tala-
mantes, 1994). However, the specifics of how these inter-
actions may function in vivo, separately or in concert,
remain to be determined.
5.4. Chorionic Somatomammotropins (CSs)
The placentae of various mammalian taxa produce
hormones that have both lactogenic and somatotropic
properties. In most taxa, these hormones are derivatives of
PRL (Schuler & Kessler, 1992; Soares & Linzer, 2001;
Soares, 2004). In primates, however, placental lactogens
are coded for by a series of genes that are part of a cluster of
GH-like genes. Genetic comparisons among primates
suggest that the duplication and possible selection events
that led to these GH-like gene clusters occurred separately
in Old World and New World primates (O. Wallis &
M. Wallis, 2002; De Mendoza, Escobedo, Davila, & Sal-
dana, 2004; Li et al., 2005). At least three of the GH-like
genes are expressed in the placenta of humans (Kliman,
Nestler, Sermasi, Sanger, & Strauss, 1986), rhesus
macaques (Golos, Durning, Fisher, & Fowler, 1993), and
baboons (Musicki, Pepe, & Albrecht, 1997). It is unknown
whether the separate duplications in New World monkeys
are also expressed by the placenta.
Chorionic somatomammotropin concentrations are
correlated with placental weight, but not fetal weight at
delivery in rhesus macaques (Novy, Aubert, Kaplan, &
Grumbach, 1981). Walker, Fitzpatrick, Barrera-Saldana,
Resendez-Perez, and Saunders (1991) report that CS has
some direct somatotropic effects on fetal tissues, alters
maternal carbohydrate and lipid metabolism, and aids in
mammary cell proliferation. Reduced CS expression in
human trophoblast is associated with intra-uterine growth
restriction in vivo and with hypoxia exposure in vitro (Roh
et al., 2005).
5.5. Corticotropin-releasing Hormone (CRH)
Corticotropin-releasing hormone was first identified as
a hypothalamic neuropeptide controlling pituitary release
of ACTH and hence affecting adrenal release of gluco-
corticoids. More recently, it has become clear that CRH
(also known as corticotropin-releasing factor (CRF)) is
expressed in other tissues and has different functions in
those tissues. Most notably, CRH is expressed in numerous
brain regions and, in primates, in the placenta. While CRH
is produced in the placentae of all anthropoid primates that
have been examined (Bowman et al., 2001; Smith et al.,
2005), it is produced at extremely low concentrations or not
at all in the placentae of other mammals (Smith et al.,
2005). The pattern of circulating CRH throughout gestation
differs between hominoid primates and monkeys: CRH
rises continuously during the final trimester in humans and
apes, peaking at term, while in monkeys it reaches its
highest concentration during midpregnancy, declining
thereafter (Goland, Wardlaw, Fortman, & Stark, 1992;
Smith, Chan, Bowman, Harewood, & Phippard, 1993;
Smith, Wickings, & Bowman, 1999; Power et al., 2006). In
contrast with hypothalamic CRH, the secretion of which is
inhibited by glucocorticoids, the secretion of placental
CRH is enhanced by cortisol, in a positive feedforward
pattern that is similar to the glucocorticoideCRH relation
in suprahypothalamic brain regions (Emanuel et al., 1994;
Smith et al., 2005). This difference appears to be due to
differential expression of transcription factors, coac-
tivators, and corepressors in hypothalamic vs. placental
tissue (King, Smith, & Nicholson, 2002).
Deviations from the typical CRH trajectory during
gestation are often associated with preterm birth in humans,
leading to the suggestion that CRH concentration may be
a marker of early placentation events that set the stage for
the rate of CRH change across gestation and the ultimate
timing of parturition (Smith et al., 2005). Placental CRH
may also affect the fetal HPA axis by stimulating fetal
ACTH release. In-vitro evidence suggests that CRH can
directly increase DHEA-S production from fetal adrenal
cells, therefore providing additional substrate for placental
estrogen production (Petraglia et al., 2005).
5.6. Leptin
Leptin was originally identified as a peptide, produced by
adipocytes, that acts upon centers in the brain controlling
satiety, energy state, and reproductive functions. Leptin is
also produced by the placenta in a number of mammalian
taxa; however, placental leptin production is significantly
higher in primates than in other mammals. In addition, the
distribution of leptin secretion to maternal vs. fetal
compartments differs between rodents and primates
(Henson & Castracane, 2002; Power & Tardif, 2005). In
humans, 95% of placental leptin is released into the
maternal circulation, suggesting that placental leptin acts
mostly on maternal physiology and directly on the placenta
rather than acting directly on the fetus (Hauguel-De
Mouzon, Lepercq, & Catalano, 2006). Primate pregnancy can
be considered a hyperleptinemic state, as leptin concentra-
tions increase early in pregnancy and remain increased over
nongravid concentrations until parturition. Local placental
309Chapter | 13 Hormones and Reproductive Cycles in Primates
effects of leptin include enhancing CG production (Char-
donnens et al., 1999) and enhancing synthetic processes
(mitogenesis, amino-acid uptake, synthesis of extracellular
matrix proteins and metalloproteinases) (Castellucci et al.,
2000; N. Jansson, Greenwood, Johansson, Powell, &
T. Jansson, 2003); i.e., regulation of placental growth. In the
mother, it is proposed that the primary function of increased
leptin concentration is to enhance mobilization of maternal
fat stores. This may be of particular importance in humans,
who produce fetuses with a relatively and absolutely larger
amount of adipose tissue than other mammals, including
other primates (Kuzawa, 1998).
6. LACTATION
Lactation is one of the defining characteristics of mammals.
Milk synthesis and secretion by mammary cells into the
alveolar lumen is a continuous process that requires PRL
(Neville, 2001). However, PRL’s influence on the process is
modified by the effects of milk removal from the lumen on
diffusion and transport processes. Release of OXY from the
posterior pituitary causes contraction of myoepithelial cells
surrounding the ducts and alveoli, forcing milk out into the
nipple, where it can be accessed by the infant (Neville,
2001). If this neuroendocrine ‘let-down’ reflex is impaired,
more milk remains in the lumen. Milk remaining in the
lumen generates local factors that adjust milk secretion. In
this way, the process of milk production is driven to a large
extent by milk demand.
Compared to other mammalian taxa, primates produce
milk that has low caloric density (i.e., high water content)
and relatively low protein content (Oftedal, 1984; Milligan,
Gibson, Williams, & Power, 2008). These features form
part of a lactation strategy that involves frequent nursing
throughout the day and night, combined with a relatively
long period of exclusive milk feeding of young; i.e.,
weaning at a relatively late age.
Another unusual feature of lactation in most primates is
the occurrence of a prolonged lactation-induced anovula-
tory period, termed lactational amenorrhea in primates that
undergo menstrual cycles. Lactation has suppressive effects
on folliculogenesis and ovulation in nonprimate mammals;
however, the extent to which lactation and subsequent
pregnancy are spaced apart by lactation is particularly
striking in primates (McNeilly, 1994). It is well established
that the suckling stimulus, rather than milk production per
se, is the driving force behind lactational effects on the
ovary. The suckling stimulus results in impaired hypotha-
lamic GnRH release that, in turn, causes impaired pulsatile
LH release from the pituitary (Weiss, Butler, Dierschke, &
Knobil, 1976; McNeilly, 1994). Given this fact, it is
perhaps not surprising that lactational infertility is greatly
lengthened in one of the few mammalian orders providing
regular and routine infant access to suckling. Primates are
one of only two mammalian eutherian lineages (the other
being Edentates) in which infants are routinely physically
carried. In most primate species this transport is performed
mostly by the mother and, as mentioned previously,
frequent bouts of suckling throughout the day and night are
a typical primate nursing pattern.
Early on, it was proposed that the hyperprolactinemia of
lactation might suppress ovarian activity by inhibiting
GnRH secretion, given the links between suckling stimu-
lation and elevated PRL release (Freeman, Kanyicska,
Lerant, & Nagy, 2000). However, the effect of PRL
manipulation on time to resumption of ovulation in
lactating macaques is variable (Maneckjee, Srinath, &
Moudgal, 1976; Schallenberger, Richardson, & Knobil,
1981), and the correlation between circulating PRL
concentration and duration of amenorrhea in lactating
women also has been inconsistent (McNeilly, 1994; Tay,
Glasier, & McNeilly, 1996). Further evidence that elevated
PRL is not a driving force behind primate lactational
anovulation is the case of the New World marmosets and
tamarins. This is the only group of primates studied so far
that does not display lactation-induced anovulation, with
most individuals in a captive setting ovulating within 9e20
days following parturition. However, they display the same
lactational hyperprolactinemia seen in other primates
(McNeilly, Abbott, Lunn, Chambers, & Hearn, 1981).
Central OXY administration inhibits LH release in
ovariectomized rhesus macaques (Luckhaus & Ferrin,
1989), but in marmosets OXY increases pituitary release of
CG, the primary pituitary luteotropic hormone of New
World monkeys (O’Byrne, Lunn, & Coen, 1990). Thus,
central OXY effects may in some way mediate GnRH-
induced LH/CG release from the pituitary and therefore
may be tied to lactational anovulation/amenorrhea. More
studies are required to define how such a mechanism might
work. Opioids and dopamine also have been proposed as
possible signals linking the suckling stimulus to GnRH
suppression; however, the factors mediating this link
remain unclear (McNeilly, 2001).
7. REPRODUCTIVE AGING
Primates, in common with many other mammals, display
an inverted-U-shaped pattern relating female fertility
parameters to age (e.g., Caro et al., 1995; Smucny et al.,
2004). Anovulation, insufficient luteolysis, and impairment
of gestational and lactational processes are all more
common at the beginning and end of reproductive life
(Atsalis & Margulis, 2008a). The extent to which late-life
reductions in fertility are specifically due to aging
neuroeendoereproductive systems is, however, quite
variable and often unclear. For example, Wright, King,
Baden, and Jernvall (2008) report that aged female sifakas
(Propithecus edwardsi), a Madagascar lemur, have
310 Hormones and Reproduction of Vertebrates
decreased infant survival, but this effect is attributed to the
females’ aging dentition and resulting inability to support
lactation. Thus, reduced fertility in old age does not, in and
of itself, demonstrate impaired neuroendocrine or gonadal
function.
Reproductive senescence will be used here to describe
the process through which the HPG axis ages, resulting
ultimately in cessation of function. vom Saal et al., (1994)
provide an excellent overview of the process of reproduc-
tive senescence in laboratory rodents, and Wise (2006)
provides a thoughtful perspective, comparing what is
known regarding reproductive aging in rodents to that of
women. Recent findings on nonhuman primate reproduc-
tive senescence, along with commentary, are found in
Atsalis and Margulis (2008a). Female reproductive senes-
cence differs among mammalian taxonomic groups. For
example, in primates, the loss of the follicular pool is the
primary event shaping the end of reproductive life,
whereas, in rodents, striking variation is seen in the size of
the follicular pool remaining at the end of reproductive life
as well as at maximum lifespan (Wise, 2006).
Within primates, human females are unusual in expe-
riencing follicular depletion relatively early in the maximal
lifespan, resulting in an extended period of altered
hormonal environments. These alterations stem from the
declining negative feedback signals from the ovary
(reduced circulating estrogens, P
4
, and inhibin), resulting in
elevated GTH concentrations for a time, followed by
declining GTHs. These hormonal changes are believed to
affect disease risks (Wise, 2006). The risk associated with
bone loss due to decreasing estrogenic activity on osteo-
blasts is well described; however, cardiovascular effects
continue to be hotly debated.
With increasing numbers of older nonhuman primates
available for study, it is now clear that monkeys and apes
also experience follicular depletion and associated
hormonal alterations (Hodgen, Goodman, O’Connor, &
Johnson, 1977; Graham, 1979; Tardif, 1985; Tardif &
Ziegler, 1992; Shideler, Gee, Chen, & Lasley, 2001;
Schramm, Paprocki, & Bavister, 2002; Atsalis & Margulis,
2008b; Videan, Fritz, Heward, & Murphy, 2008). However,
the stage of life at which this occurs is generally later than
that observed in humans (see Table 13.1). Atsalis and
Margulis (2008b), in reviewing the data on monkeys and
apes, conclude that ‘potentially up to 25% of a female’s life
can be post-reproductive’ (p 140). This claim is made in
reference to maximal lifespan; in comparison, a human
female living the maximal lifespan (now around 120 years)
will spend around 58% of her life in a postreproductive
state. When compared to average lifespan, as opposed to
maximal lifespan, most nonhuman female primates will die
at or before the point at which reproductive senescence
begins. These comparisons have been controversial and
will continue to be refined, given the oft-made claim that
human female reproductive aging is unique and may be
driven by indirect fitness advantages to postreproductive
women providing resources to grandchildren; i.e., the
grandmother hypothesis (Hill & Hurtado, 1991; Hawkes,
1997; Alvarez, 2000; Peccei, 2001a; 2001b).
Male primates, in common with many other male
mammals, display decreases in circulating T concentrations
with age (Ellison et al., 2002; Hardy & Schlegel, 2004;
Tardif et al., 2008). Data from men and male rodents
indicate reduced GnRH pulse amplitude with age, though
LH concentrations do not decline. Old marmoset males
have lower excreted T and appear to be hyper-responsive to
exogenous GnRH stimulation. These findings, taken
together, suggest that age-related changes in hypothalamic
function may be important drivers of reduced T concen-
tration with age.
8. SEXUAL BEHAVIOR
8.1. Description
Compared to other mammals, sexual behavior in primates
is noteworthy for its flexibilitydnot so much with respect
to the behavioral patterns used in courtship and copulation,
but in the relative independence of these behaviors from
hormonal control, especially in females. Here we describe
the behavioral patterns commonly exhibited during primate
courtship and copulation, and then discuss the role of
steroid hormones in regulating these behaviors. For
a comprehensive review of these and other aspects of
primate sexual behavior, see Dixson (1998).
Most primate species exhibit fairly stereotyped dorso-
ventral mounting postures, similar to other mammals
(Dixson, 1998; Campbell, 2007). Numerous variations are
seen, however; e.g., the male and female may sit, stand, or
hang from tree branches while mating, and may even
copulate while suspended upside-down (e.g., aye-aye
(Daubentonia madagascariensis)). Males use a variety of
methods to stabilize themselves against females, including
single- and double-foot clasp mounting, in which the male
uses one or both feet to grip the female’s ankles or legs
(e.g., macaques, baboons); the leg-lock, in which a male
positions his legs over the female’s thighs (e.g., spider
monkeys (Ateles spp.); brown woolly monkeys (Lagothrix
lagotricha)); and manual grasping of the female’s hips or
waist (e.g., tamarins (Saguinus spp.); owl monkeys (Aotus
spp.)) (Dixson, 1998). Ventro-ventral copulation is seen in
a number of apes, and two species, human beings and
bonobos, exhibit even more varied repertoires of copulatory
positions.
Primate species differ markedly in the number and
duration of intromissions prior to ejaculation (Dixson,
1998), although the most common pattern involves
a single, brief intromission. For example, pygmy
311Chapter | 13 Hormones and Reproductive Cycles in Primates
marmosets (Cebuella pygmaea) exhibit a single intro-
mission lasting four to ten seconds and involving only
several quick pelvic thrusts (Soini, 1988). In contrast,
muriquis (Brachyteles arachnoides) perform an extended
intromission, lasting an average of four minutes and
consisting of a prolonged immobile period followed by
five to ten pelvic thrusts and ejaculation (Milton, 1985),
whereas rhesus macaques perform a series of up to
twenty or more brief mounts, each lasting one to fourteen
seconds, with two to fifteen pelvic thrusts per mount
(Shively, Clarke, King, Schapiro, & Mitchell, 1982).
Males and females often separate immediately or shortly
after ejaculation, but in several species the male may
remain intromitted for up to two minutes (stumptail
macaque (Macaca arctoides)(Goldfoot et al., 1975)) or
even several hours after ejaculation (thick-tailed greater
galago (Otolemur crassicaudatus)(Eaton, Slob, & Resko,
1973)), suggesting the possibility of a genital lock.
Male primates use a variety of behaviors to initiate
sexual interactions with females, including eye contact;
specialized facial movements or expressions; approaches
toward or following of the female; visual, olfactory, or oral
investigation of the female’s genitalia or sexual skin; and
specific locomotor patterns (Dixson, 1998). Female sexu-
ality, as described by Beach (1976), can be divided into
three major components: attractivity (the female’s attrac-
tiveness or stimulus value to a particular male), proceptivity
(the female’s behavioral role in initiating copulation), and
receptivity (the female’s willingness to copulate). Attrac-
tivity in primates may be based on both behavioral and
nonbehavioral stimuli from females, including proceptive
behaviors, sexual skin swellings in many Old World
monkeys and apes, and olfactory cues in many prosimians
and New World monkeys. Proceptivity is often a particu-
larly striking aspect of primate sexual interactions. Females
use a number of behaviors to arouse males’ interest and
solicit mating, including facial displays, specific body
postures such as the ‘sexual present’ (presenting the ano-
genital region to the male), specialized vocalizations, and
touching or even mounting the male (reviewed by Dixson,
1998). Sexual receptivity is manifest in stereotyped lordotic
postures in at least some prosimian species, whereas female
anthropoids do not exhibit lordosis. Consequently, recep-
tivity in anthropoids is typically inferred from females’
patterns of permitting, avoiding, refusing, or terminating
mount attempts by males (Dixson, 1998).
8.2. Hormonal Influences on Sexual Behavior
As in other male mammals, sexualbehavior in male primates,
including men, is clearly influenced by androgens. Male
sexual behavior tends to correlate with circulating androgen
concentrations both across the lifespan and, in seasonal
breeders, across the annual reproductive cycle (Dixson,
1998). Castration generally decreases frequencies of sexual
behavior, especially intromission and ejaculation, whereas T
replacement reverses these effects. Both men and monkeys,
however, exhibit pronounced interindividual variation in
their responses to castration: while some individuals show
rapid declines in, orcomplete obliteration of, sexual behavior
following castration, others show a moregradual cessation of
sexual behavior, and still others continue to exhibit virtually
normal sexual behavior even years later (Hull, Wood, &
McKenna, 2006). Testicular androgens do not, therefore,
appear to be essential for the expression of male sexual
behavior, in at least some individuals.
The mechanisms by which androgens influence sexual
behavior in male primates are not fully understood. In
rodents, activational effects of androgens are mediated by
intracellular aromatization of androgens to estrogens within
the brain and subsequent binding to ERs. In primates, little
evidence exists to support a critical role of aromatization in
male sexual behavior; however, this issue has been
addressed in only a small number of primate species, and
therefore remains unresolved (Dixson, 1998; Wallen, 2005;
Hull et al., 2006). Finally, P
4
inhibits male sexual behavior
in both men and macaques (Hull et al., 2006).
Female sexual behavior in nonprimate mammals is
typically exhibited only during the periovulatory period
and is critically dependent on stimulation by ovarian steroid
hormones. Prosimians appear to follow a similar pattern:
females are sexually receptive during a limited period
around ovulation ein some cases, only several hoursdand
ovariectomy abolishes female sexual behavior (Van Horn &
Eaton, 1979; Dixson, 1998). In contrast, sexual behavior in
anthropoid primates is characterized by its emancipation
from strict regulation by gonadal hormones: females may
engage in sexual activity at any point in the ovarian cycle,
during pregnancy, or even following ovariectomy or
menopause (Dixson, 1998; Campbell, 2007). Although
such findings demonstrate that the expression of sexual
behavior in female primates is not dependent upon gonadal
hormones, other evidence indicates that female sexual
behavior can, none-the-less, be influenced by them. In
many New World monkeys, Old World monkeys, and apes,
females show periovulatory peaks in copulatory behavior,
associated with increases in proceptivity, attractivity, and,
to a lesser extent, receptivity (Dixson, 1998). Moreover,
ovariectomy decreases, and estrogen replacement restores,
sexual behavior in a number of species. Again, proceptivity
often shows a clear relationship with hormonal status in
these studies, whereas effects on receptivity are much less
pronounced (Dixson, 1998).
In contrast to estrogens, progestogens tend to reduce
receptivity, proceptivity, and attractivity in female
primates. Finally, androgens of ovarian and/or adrenal
origin have been implicated in stimulating both receptivity
and proceptivity in female primates, especially rhesus
312 Hormones and Reproduction of Vertebrates
macaques and women; however, findings have been mixed,
and the role of ovarian or adrenal androgens in female
sexual behavior remains unclear (Dixson, 1998; Johnson &
Everitt, 2000). A particularly controversial issue has been
whether estrogens and other steroid hormones influence
female sexual activity through peripheral (e.g., sexual skin,
olfactory cues) and/or central (i.e., brain) actions. Current
evidence suggests that estrogens act peripherally to
enhance attractivity, whereas estrogens, progestogens, and
androgens may all act centrally to modulate receptivity and
proceptivity (Dixson, 1998).
The relationship between the ovarian cycle and sexual
behavior in female primates may be influenced profoundly by
the environment, especially the social environment. For
example, orangutans and rhesus macaques show
a pronounced peak in copulatory frequency during the peri-
ovulatory period under conditions in which females can
control access to males, but not when females and males are
‘forced’ to interact in free-access pair tests (Wallen, 1990;
Dixson, 1998). Similarly, periovulatory peaks in proceptivity
and copulation are much more pronounced in rhesus
macaques tested in a grouped (multi-female, single-male)
situation than when males and females are tested as isolated
pairs (Wallen, 1 99 0). Such findings may reflect the use of
sexual behavior for nonreproductive functions, the relative
abilities of males and females to control sexual interactions
under different environmental conditions, and increased
agonistic interactions among females of some species (e.g.,
rhesus macaques) during sexual interactions with males
(Wallen, 1990; Dixson, 1998). Wallen (1990) has interpreted
such findings as evidence that ‘hormones influence the sexual
motivation required to initiate sexual activity in social
circumstances requiring social effort’ (p 239). Clearly, in
contrast to rodents, in which ovarian steroids are essential for
both sexual motivation and sexual performance (i.e.,
lordosis), ovarian (and possibly adrenal) steroids are not
necessary for copulation in female anthropoid primates but
may be one of several important factors influencing sexual
desire.
9. ENVIRONMENTAL INFLUENCES ON
REPRODUCTION
9.1. Reproductive Seasonality
Seasonal changes in the environment have long been
known to affect reproduction in mammals. Outstanding
comparative reviews of both proximate and ultimate
aspects of mammalian reproductive seasonality are
provided by Bronson (1989) and Malpaux (2006). For
mammals in temperate regions, with strong circannual
variation in both day length and temperature, the time of
year at which various reproductive activities (mating,
pregnancy, lactation) occur is often quite predictable, with
dramatic differences in HPG function in breeding vs.
nonbreeding seasons. Mammals adapted to tropical regions
might be expected to have less striking reproductive sea-
sonality, and that is the case with primates. The majority of
primate species are restricted to tropical regions, macaques
and humans being the best-studied exceptions. Primates
exhibit an amazing array of seasonal patterning (see Table
13.1), ranging from predictable, relatively narrow breeding
seasons, to seasonal, but quite variable, birth peaks, to no
evidence of any seasonality. A comparison of these
examples suggests that phylogeny is a poor predictor of
these traits. While most prosimians are strongly seasonal
and apes are generally not seasonal, the degree of season-
ality in New World and Old World monkeys ranges from
strong to nonexistent in a manner that is not explained by
phylogeny within these groups.
Two primate genera with strongly seasonal patterns are
the Central and South American squirrel monkeys (Saimiri)
and the northernmost macaques (Macaca), such as rhesus
macaques and Japanese macaques (M. fuscata). In these
species, females either ovulate irregularly or fail to ovulate
altogether during the nonbreeding season. Studies have
suggested both central changes in GnRH pulsatility (Hen-
drickx & Dukelow, 1995) and direct changes in ovarian
function (Hutz, Dierschke, & Wolf, 1985) as possible
factors in seasonal anovulation of female rhesus macaques,
but the exact mechanisms have not been fully elucidated. In
squirrel monkeys, reductions in FSH secretion appear to
underlie the seasonal shift from an ovulatory to an anovu-
latory pattern (Kuehl & Dukelow, 1975).
In both squirrel monkeys and rhesus macaques, males
also display a seasonal pattern of T production, with peaks
occurring as the mating season commences. Both squirrel
monkey and macaque males display T-supported charac-
teristics that arise during the breeding season. Male squirrel
monkeys undergo weight gain of around 14%, caused
largely by retention and deposition of water along the arms,
shoulders, and back (Jack, 2007), as well as increases in
testicular volume of 150% (Wiebe et al., 1988). During the
nonbreeding season, male rhesus macaques display reduced
LH pulsatility, reduced diurnal rhythms in pulsatility,
regression of seminiferous tubules, and few spermatocytes
or spermatids. In the months leading into the mating season,
LH pulsatility increases, seminiferous tubular diameter
increases, and spermatogenesis commences (Wickings &
Nieschlag, 1980; Wickings, Marshall, & Nieschlag, 1986).
Breeding males also display skin reddening, likely related to
increasing T production.
The roles of specific environmental cues in generating
these neuroendocrine changes in squirrel monkeys and
rhesus macaques remain obscure; however, changing day
length cues do not appear necessary, as the patterns are
retained in controlled day length conditions (Wehrenberg &
Dyrenfurth, 1983).
313Chapter | 13 Hormones and Reproductive Cycles in Primates
Circannual variation in the tropical environment is most
strongly tied to rainfall that, in turn, generates seasonal
variation in food availability. Where there is birth season-
ality, births usually occur in the dry season; however, there
are exceptions (e.g., Struhsaker & Leland, 1987). As
a result of long gestation and lactation periods, primates
cannot limit all reproductive investment to a single cir-
cannual period. For example, if weaning of infants is to
occur during a period of relative food abundance, then other
aspects of the reproductive cycle, such as mating and
gestation, may occur during periods of relative food scar-
city. Numerous attempts have been made to model the
manner in which selective pressures may have shaped these
responses, but no single model explains the wide variation
seen in primate breeding schedules (Van Schaik & Brock-
man, 2005).
It is possible that some seasonal patterning results from
alterations in physical activity or food availability. In
women, e.g., high levels of physical activity are associated
with suppressed ovarian function (Jasienska & Ellison,
2004). The increased day range lengths and home range
sizes seen in some primate species during times of scarcity
(Hemingway & Bynum, 2005) may inhibit HPG axis
activity through altering energy balance or stress (See
Section 9.3).
9.2. Social Influences on Reproduction
Primates exhibit a broad diversity of social systems,
including a dispersed, relatively solitary lifestyle; social
monogamy and nuclear family units; single-male, multi-
female groups; and multi-male, multi-female societies,
some of which may undergo complex fission/fusion
patterns. In each of these social configurations, reproduc-
tive function of females, and in some cases males, may be
modulated by salient social cues. The nature and magnitude
of these socioendocrine effects, as well as the behavioral or
sensory cues eliciting them, vary markedly among species,
sexes, and social systems. In general, though, both males
and females often exhibit enhanced activity of the HPG
axis in response to interactions with or cues from unrelated,
opposite-sex adults, and inhibition of HPG activity in
response to same-sex adults, especially those of higher
dominance status. Such effects may influence the course of
reproductive maturation in adolescents, or may alter or
even abolish fertility in fully mature adults. Below we
describe some of the best-studied examples in each sex.
9.2.1. Males
9.2.1.1. Social influences on reproductive
maturation in males
In several primate species, the timing and/or trajectory of
reproductive maturation in males is reported to be
influenced by the social environment. Most commonly,
adolescent males of high dominance status, or those with
high-ranking mothers, have been found to undergo earlier
puberty and to have higher circulating or excreted T
concentrations and larger testes, compared to lower-
ranking males. Among captive rhesus macaques, e.g., both
plasma T concentrations and testicular mass (either abso-
lute or corrected for body mass) in adolescent males tend to
correlate with the males’ dominance status, especially at
the outset of the mating season (Bercovitch, 1993; Dixson
& Nevison, 1997). Moreover, adolescent males with high-
ranking mothers or from high-ranking matrilines have
higher plasma T levels and heavier testes, and may attain
puberty earlier, than those with lower-ranking mothers
(Dixson & Nevison, 1997; Mann, Akinbami, Gould, Paul,
& Wallen, 1998).
Similar patterns have been described in semi-free-
ranging mandrills, in which adolescent males that were
relatively high-ranking for their age had higher circulating
T levels, larger testes, and greater development of
secondary sexual characteristics (sexual skin coloration and
activity of the sternal scent gland) than lower-ranking
adolescents (Setchell & Dixson, 2002). In free-ranging
baboons (Papio cynocephalus), the onset of puberty, as
determined by the age of testicular enlargement, was
significantly correlated with maternal rank, with sons of
high-ranking females undergoing testicular enlargement up
to a year earlier than sons of low-ranking females (Alberts
& Altmann, 1995). Interestingly, the age at testicular
enlargement is also advanced in sons of high-ranking males
if their father remains in the same social group during the
son’s juvenile development (Charpentier, Van Horn, Alt-
mann, & Alberts, 2008b).
Social modulation of male reproductive development is
especially pronounced in the orangutan. In both wild and
captive populations, adolescent males living in proximity to
fully adult males often, but not always, exhibit delayed
development of secondary sexual characteristics, including
cheek flanges, laryngeal sac, beard and mustache, musky
odor, and large body size (Kingsley, 1982; Maggioncalda,
Sapolsky, & Czekala, 1999; Setchell, 2003). Such ‘devel-
opmentally arrested’ adolescents are fertile and may sire
offspring; however, they appear to be sexually unattractive
to females and may commonly force copulations (Utami,
Goossens, Bruford, De Ruiter, & Van Hooff, 2002). These
males exhibit significantly reduced urinary concentrations
of T, DHT, LH, cortisol, and PRL (but not FSH), as
compared to adolescents undergoing development of
secondary sexual characteristics (Maggioncalda et al.,
1999; Maggioncalda, Czekala, & Sapolsky, 2002). The
precise role of adult male orangutans in suppressing
reproductive maturation in adolescents has not been tested
experimentally; however, anecdotal evidence from both
captive and free-living orangutans indicates that, after the
314 Hormones and Reproduction of Vertebrates
removal or disappearance of a nearby, fully developed adult
male, arrested adolescents may rapidly resume sexual
development and attain full maturation within several
months, even after a period of developmental arrest lasting
20 years or more (Maggioncalda et al.,1999; Utami, 2000,
cited in Setchell, 2003).
9.2.1.2. Social influences on reproduction in adult
males
Reproductive function of adult males can be influenced by
both intrasexual and intersexual stimuli in a wide variety of
primates. Typically, interactions with or cues from other
adult males dampen activity of the HPG axis, while inter-
actions with or cues from adult females have stimulatory
effects. These two classes of socioendocrine effects may
interact with each other and with responses to other envi-
ronmental cues (e.g., photoperiod) in complex ways.
One of the best-studied examples is the gray mouse
lemur (Microcebus murinus), a small, nocturnal, relatively
nonsocial prosimian (reviewed in Perret, 1992). In captive,
mixed-sex social groups, middle- and low-ranking males
engage in very little sexual behavior and exhibit low circu-
lating T concentrations during the annual mating period, as
compared to dominant males. Moreover, circulating levels
of sex hormone-binding globulin are elevated in middle- and
low-ranking males, further reducing the bioavailability of T
to the tissues. Circulating cortisol concentrations do not
differ among high-, middle-, and low-ranking males but are
elevated in all group-housed males, as compared to socially
isolated males, suggesting that social housing per se, but not
necessarily subordination, is stressful.
Circulating T levels in male gray mouse lemurs are
modulated by a chemosignal found in the urine of socially
dominant or isolated males (Perret, 1992). Interestingly,
response to the male chemosignal varies across the annual
cycle (Perret & Schilling, 1995). During the onset of
photoperiodic stimulation (i.e., long days, as would occur
at the outset of the breeding season), exposure to urine from
an isolated or dominant male reduces T levels in other
males. During continued exposure to long day lengths (i.e.,
later in the breeding season), exposure to male urine delays
testicular regression and the decline in T levels that would
normally result from photorefractoriness. Finally, during
exposure to inhibitory short days (i.e., the nonbreeding
season), exposure to male urine stimulates testicular
recrudescence and markedly elevates plasma T levels.
Under any of these photoperiodic conditions, circulating T
levels can be increased in males by exposure to chemo-
signals from females, especially during the females’
proestrus period. The neuroendocrine mechanisms medi-
ating these stimulatory and inhibitory social effects are not
fully understood but appear to involve both PRL and the
endogenous opioids (Perret, 1992).
Circulating T concentrations in males are similarly
influenced by social partners of both sexes in the squirrel
monkey, a seasonally breeding New World primate that
lives in large, multi-male, multi-female groups. In captivity,
plasma T levels are higher in males housed with multiple
females than in males housed with only a single female, and
are higher in dominant males than in intermediate- and low-
ranking males (Mendoza, Coe, Lowe, & Levine, 1979;
Schiml, Mendoza, Saltzman, Lyons, & Mason, 1996).
None-the-less, seasonal changes in T, as well as in circu-
lating cortisol levels and body mass, occur in all males,
regardless of social rank or access to females (Schiml et al.,
1996; Schiml, Mendoza, Saltzman, Lyons, & Mason,
1999). Importantly, inter-individual differences in T levels
result from, rather than cause, differences in rank: male T
levels prior to group formation do not predict subsequent
attainment of social status, but increase in dominant males
and decrease in subordinates following both formation of
all-male groups and introduction of females (Mendoza
et al., 1979).
9.2.2. Females
Reproductive attempts are considerably more costly for
female mammals than for males, as a consequence of the
physical constraints and energetic demands imposed by
pregnancy, lactation, and maternal behavior. Consequently,
females are likely to undergo more intensive selection than
males to initiate breeding attempts under auspicious envi-
ronmental conditions, and hence to take advantage of
environmental cues indicative of conditions favorable for
infant survival, including cues arising from the social
environment (Wasser & Barash, 1983). Not surprisingly,
therefore, females across a wide range of primate taxa
exhibit clear reproductive responses to social variables. As
with males, social factors can modulate the timing and
trajectory of reproductive maturation in young females, as
well as reproductive physiology in fully mature adults.
9.2.2.1. Social influences on reproductive
maturation in females
In several primate species, interactions with or cues from
unrelated adult males advance puberty in young females.
Female Garnett’s greater galagos and Senegal lesser bush
babies (Galago senegalensis), e.g., undergo their first
vaginal estrus significantly earlier if pair-housed with an
adult male than with a peer male (Izard, 1990). Similarly,
cohabitation with a stepfather has been associated with
earlier puberty in human girls (Ellis & Garber, 2000).
As in male primates, interactions with or cues from
same-sex conspecifics tend to delay puberty in females.
Among captive rhesus macaques, e.g., age at menarche is
not associated with dominance status, but high- and
middle-ranking females undergo their first ovulation at
315Chapter | 13 Hormones and Reproductive Cycles in Primates
significantly younger ages than low-ranking females
(Schwartz, Wilson, Walker, & Collins, 1985; Zehr, Van
Meter, & Wallen, 2005). In free-ranging baboons (P. cyn-
ocephalus), menarche occurs earlier in daughters of high-
ranking females than in daughters of low-ranking females
(Bercovitch & Strum, 1993; Wasser, Norton, Kleindorfer,
& Rhine, 2004; Charpentier, Tung, Altmann, & Alberts,
2008). Earlier menarche in baboons is also associated with
a number of additional social factors, including living in
a group with more maternal half-sisters or fewer adult
females, and a longer period of coresidency with the father
during the daughter’s juvenile period (Charpentier et al.,
2008a; 2008b). The mechanisms underlying such social
modulation of female reproductive maturation are not
known but have been suggested to involve differences in
nutritional status, body mass, or psychosocial stress (Ber-
covitch & Strum, 1993; Wallen & Zehr, 2004; Zehr et al.,
2005).
9.2.2.2. Social influences on reproduction in adult
females
Social cues influence ovarian cycle dynamics in adult
females of several primate species. In gray mouse lemurs,
both tactile and distal cues from other females cause
lengthening of the ovarian cycle, associated with an
increase in luteal-phase length and a decrease in plasma P
4
concentrations (Perret, 1986). In women, axillary secretions
both from other women and from men have been implicated
in modulating the ovarian cycle. Axillary secretions taken
from women in the late follicular phase increase LH pulse
frequency, advance the timing of the preovulatory LH surge,
and shorten ovarian cycle length in recipients, whereas
axillary secretions collected from women during the
ovulatory phase of the cycle produce the opposite effects
(Stern & McClintock, 1998; Shinohara, Morofushi, Funa-
bashi, & Kimura, 2001). Collectively, these effects might
underlie the pattern of menstrual synchrony documented in
many, but not all, studies of women roommates, friends, and
coworkers (Weller & Weller, 1993). Luteinizing hormone
pulse frequency is also increased in women exposed to
axillary secretions from men (Preti, Wysocki, Barnhart,
Sondheimer, & Leyden, 2003).
Perhaps the most dramatic example of social regulation
of reproduction in female primates is reproductive
suppression in the Callitrichidae (marmosets and tamarins).
These small New World monkeys live in groups of
approximately 4e15 individuals, which may include
several adults of each sex as well as juveniles and infants.
In most species of callitrichid, however, only a single,
behaviorally dominant female breeds in each social group
(Digby, Ferrari, & Saltzman, 2007). Subordinate females
fail to breed, as a result of social suppression of ovulation
and/or inhibition of sexual behavior, and instead serve as
nonreproductive alloparents, helping to rear the infants of
the dominant female. The mechanisms underlying this
social control of fertility, or ‘social contraception’ (Abbott,
1984), differ among species (French, 1997) but have been
studied most thoroughly in the common marmoset
(reviewed by Abbott, Digby, & Saltzman, 2009; Saltzman,
Digby, & Abbott, 2009). Most subordinate females in
laboratory groups of common marmosets, and at least some
in wild groups, fail to ovulate and exhibit impairments in
ovarian steroidogenesis and follicular development. These
deficiencies in ovarian function, which may last for periods
of up to several years or more, are caused by suppressed
pituitary secretion of CG, which is released by the anterior
pituitary instead of LH in this species (see Section 2.1). The
exact mechanism underlying CG inhibition is not yet
known; however, it appears to be associated with enhanced
negative-feedback sensitivity of the brain and/or pituitary
to low levels of estrogen, blunted responsiveness to
estrogen positive feedback, and enhanced CG inhibition by
endogenous opioids. Surprisingly, however, CG suppres-
sion does not appear to be associated with altered hypo-
thalamic secretion of GnRH and is not accompanied by
manifestations of generalized stress (Abbott et al., 2009;
Saltzman et al., 2009).
9.3. Energetics of Reproduction
9.3.1. Introduction
The mammalian reproductive system is adept at monitoring
maternal condition and parsing the energy available for
gamete production, fetal growth, and infant growth. The
manner in which maternal energetic state is sensed and
signals are processed to alter reproductive function has
been a particularly active area of research for the past two
decades. A good part of that research interest has been
driven by the discoveries of a variety of endocrine and
autocrine factors produced by adipose tissue, as well as
identification of new hormones produced by the gastroin-
testinal tract, all offering a myriad of possible cues of
metabolic state (Wade, Schneider, & Li, 1996; Baird,
Cnattingius, Collins, & Evers, 2006; Tena-Sempere, 2007;
Roa et al., 2008).
From the standpoint of tradeoffs, one would expect that
early stages of reproduction, including ovulation, placen-
tation, and fetal growth, might be more plastic in response
to maternal energy stores than lactation because of the
extent of investment already made late in the reproductive
event. The ability of the mother to ‘cut bait’ early in
investment and save energy stores for future investment
might offer more of a selective advantage the earlier in
reproduction this event occurs. Later investment, including
lactation, by which time the primate mother has already
invested large amounts of energy and time in the infant,
316 Hormones and Reproduction of Vertebrates
should be less responsive to changes in maternal energy
stores, enhancing the likelihood that the mother’s invest-
ment (i.e., the offspring) survives. Therefore, certain stages
of placental, fetal, and infant development may be more
affected by changes in maternal status than others, and the
manner in which autocrine, paracrine, and hormonal factors
convey information regarding maternal energy state differs
among the following points at which a female mammal
might adjust investment: ovarian folliculogenesis leading
to ovulation; placental transfer of resources from mother to
fetus; and mammary gland transfer of resources from
mother to infant. What follows is a discussion of autocrine/
endocrine signals that may act at different points in the
primate reproductive cascade to signal energy excess or
deficit.
9.3.2. Energetics of hypothalamicepituitary
function
The cellular processes leading to maturation of game-
tesdboth sperm and ovadare controlled by central
nervous system mechanisms that respond to both negative
feedback and positive feedforward from steroids and other
hormones produced by the gonads. The basics of this HPG
axis control system have been relatively well characterized
for some time. More recent research has begun to better
characterize those signals that may alter pituitary GTH
releasedthrough either altered hypothalamic GnRH pulse
generation or direct effects on the pituitarydand thus alter
the production and release of gametes. Recently identified
signals that may indicate energetic state include leptin,
produced in adipose tissue, and ghrelin, produced in the
gastrointestinal tract.
As circulating leptin concentration is correlated with
the amount of adipose tissue, leptin can function as a signal
of stored energy availability. As such, the impact of leptin
in the central nervous system is generally to reduce food
intake and to enhance reproduction. Studies in rodents,
monkeys, and humans reveal that leptin exposure stimu-
lates pituitary LH release (Tena-Sempere, 2007). Normal
pulsatile release of LH and FSH can be restored by leptin
treatment in calorie-deprived women (Schurgin, Canavan,
Koutkia, Depaoli, & Grinspoon, 2004). In rats, intra-
hypothalamic infusion of leptin alters GnRH pulse gener-
ation (Watanobe et al., 2002), but there is also evidence of
direct effects of leptin upon pituitary gonadotropes. The
interaction of leptin with GnRH neurons may be mediated
by Kp (Tena-Sempere, 2007). While the overall picture of
leptin as an energy signal is one in which leptin supports
reproduction, leptin also has been found in some studies to
perform actions that may impair GTH release (see also
Section 9.3.3). In addition, studies of human obesity indi-
cate that individuals with extremely high adiposity may
become leptin-resistant. The full picture of the manner in
which leptin, alone or in concert with other signals, alters
HPG axis function remains, therefore, to be elucidated.
As opposed to leptin, the peptide ghrelin, produced by
the gastrointestinal tract, is a potent orexigenic stimulus in
the hypothalamus and has been proposed as a signal of
energy insufficiency. Ghrelin, like leptin, affects repro-
ductive aspects of HPG axis function as well as food intake.
Administration of ghrelin inhibits LH pulsatility in rodents
and monkeys (Vullie
´moz et al., 2004). Recent studies
suggest that this effect may be mediated by the HPA axis:
ghrelin induces elevations in circulating glucocorticoid
concentrations, and inhibition of this action abolishes
ghrelin’s ability to alter LH pulsatility (Vullie
´moz, Xiao,
Xia-Zhang, Rivier, & Ferin, 2008).
9.3.3. Energetics of gonadal function
The actions of the HPG axis on folliculogenesis and
ovulation are mediated by a large number of peptide
signals, many of which are produced in the ovary. Some of
these signaling systems are reasonable prospects as
possible metabolic cues. A primary example is the IGF
system. Insulin-like growth factor-1 and IGF-2 are present
in follicular fluid, as are five of the six IGF-binding proteins
that control cellular access to IGFs. Locally produced IGF
and local control of IGF-binding proteins are proposed to
regulate the development and/or atresia of antral follicles
(Giudice, 2001). However, because circulating IGF is
controlled by GH, a hormone that is sensitive to energy
state, the IGF system that mediates folliculogenesis also
may be affected by energy state.
In contrast to the hypothalamus and pituitary, where
leptin and ghrelin have largely opposing effects, the direct
effect of both of these peptides on the gonads is to inhibit
production of steroids (T in the testis, E
2
in the ovary). In
addition, expression and immunostaining studies indicate
that ghrelin is produced by the gonads, as well as by the
gastrointestinal tract (Tena-Sempere, 2007). The manner in
which leptin and ghrelin exert local effects on primate
gonads remains to be elucidated.
9.3.4. Energetics of pregnancy
Pregnancy represents a peculiar environment in which the
short- and long-term reproductive interests of the mother
are played out withdor againstdthe short-term interests of
the fetus. Variation in placental structure and function are
mechanisms through which the mother may alter invest-
ment in the fetus, but they are also mechanisms through
which the fetus may manipulate maternal investment (Haig,
1993; 1996; Crespi & Semeniuk, 2004). For example,
increases in litter size in the common marmoset are
accompanied by a dramatic expansion of the placental
interface, which is the site of fetomaternal nutrient and
317Chapter | 13 Hormones and Reproductive Cycles in Primates
hormonal exchange (Rutherford & Tardif, 2009). As the
placenta has the same developmental legacy and genomic
identity as the fetus, this functional plasticity has important
implications for metabolic and hormonal signaling.
Placental growth is driven mostly by placentally
derived growth factors, the most important being IGF-2,
and mostly is inhibited by maternal factors (Lewis,
Morlese, Sullivan, & Elder, 1993; Crossey, Pillai, &
Miell, 2002). In nonprimates, deficiency of IGF-1 or IGF-
2 results in a reduction in birth weight (Fowden, 2003;
Gicquel & LeBouc, 2006). In cases of intrauterine growth
restriction (IUGR), there is often a higher fetal : placental
weight ratio, suggesting that the placenta may actually be
more efficient in the transport of nutrients (Consta
ˆncia
et al., 2002; Rutherford & Tardif, 2008), even though that
increased efficiency is ultimately insufficient to sustain
normal growth. Deficiency in IGF-2 leading to IUGR
may be associated with upregulation of amino acid
transport systems (Consta
ˆncia et al., 2002), indicating
a specific role for placental hormonal signals in directing
fetal metabolic pathways.
Two other placental hormones, GH and leptin, have
been proposed to mediate a maternal insulin resistance
and, therefore, a shift toward reliance on lipolysis for
energy production. In humans, reduced placental GH and,
therefore, reduced maternally produced IGF-1 is associ-
ated with IUGR (Lacroix, Guibourdenche, Frendo,
Muller, & Evain-Brion, 2002). At the other end of the
spectrum, gestational diabetes in humans is associated
with markedly higher concentrations of placental leptin,
and leptin pathways have been suggested as one of the
possible mechanisms underlying diabetes-induced fetal
macrosomia (i.e., birth weight 4000 g) (Hauguel-de
Mouzon et al., 2006).
While numerous studies describe the relations among
maternal condition and birth outcomes in primates,
including humans (e.g., Lee, Majluf, & Gordon, 1991;
Bowman & Lee, 1995; Fairbanks & McGuire, 1995; Ber-
covitch, Lebron, Martinez, & Kessler, 1998; Johnson,
2003), there are few primate studies in which maternal
condition has been manipulated systematically. One such
study was conducted in captive common marmoset
monkeys exposed to a modest (25%) restriction of energy
intake during either mid or late pregnancy. This restriction
resulted in abortion of all mid-term pregnancies. Maternal
urinary concentrations of CG, cortisol, and free E
2
were all
lower in the restricted pregnancies, suggesting that the
change in maternal energy availability resulted in impaired
placental function. Restrictions in late pregnancy did not
reliably induce pregnancy loss, though the number of
preterm deliveries was higher than expected (Tardif, Power,
Layne, Smucny, & Ziegler, 2004; Tardif, Ziegler, Power, &
Layne, 2005). The extreme outcome in the face of a rela-
tively modest restriction at midpregnancy suggests that
placental formation and function in this very small primate
is quite sensitive to maternal energy state. In contrast,
a similar level of food restriction in captive baboons
affected placental weight but not fetal growth (Schlabritz-
Loutsevich et al., 2007), with fetal growth perhaps pro-
tected by decreased maternal activity and increased use of
maternal stores.
9.3.5. Energetics of lactation
Given the time and energy investment represented by the
primate neonate, one might propose that maternal post-
parturition investment would be somewhat less sensitive to
maternal condition. Neville (2001) states that, ‘unlike the
nutrition received by the fetuses through the placenta, the
nutrition received by breastfed infants is not dependent upon
the status of maternal metabolism. For most milk compo-
nents, the secretory mechanisms are insulated from the
regulatory mechanisms that control nutrient flux in mothers,
so sufficient milk of adequate composition is available to
infants even during inadequate food intake by mothers.’
(p 20). Studies of primate milk are limited to a few species,
with most studies being done in humans. While intra- and
inter-species variation in relative fat content and, therefore,
in energy density is a common finding (Power, Oftedal, &
Tardif, 2002; Milligan et al., 2008), a complete failure of
milk production is rare, supporting Neville’s contention that
milk production is more insulated from maternal insults. In
lactating common marmosets that had either variable energy
demand (e.g., nursing singletons vs. twins) or variable
maternal energy availability (e.g., different maternal nutri-
tive conditions or maternal energy restriction), the combi-
nation of high energy demand and low maternal stored
energy availability resulted in slower growth of infants, but
in no case did mothers cease investment (i.e., stop lactating)
(Tardif, Power, Oftedal, Power, & Layne, 2001; Tardif &
Ross, 2009).
Perhaps the largest effects of maternal condition on
lactation are noted in relation to the time to weaning. Lee
et al. (1991) proposed that weaning in primates was related
to attainment of critical weights, so that slower-growing
infants (e.g., infants of mothers with lower milk energy)
would be expected to be weaned at later ages. As the
mother’s milk production is driven by the relative amount
of emptying of the alveolar lumen, the lactating mother and
the nursing infant make up a complex, behaviorally driven
feedback system.
10. CONCLUSIONS AND FUTURE
DIRECTIONS
Primates are morphologically generalized mammals that
are distinguished by their large brains, advanced cognitive
abilities, flexible behavior, sophisticated social systems,
318 Hormones and Reproduction of Vertebrates
and long lives (Hartwig, 2007; Zimmermann & Radespiel,
2007). Although primate species exhibit marked diversity
in morphology, ecology, life-history parameters, and social
organization, they share a reproductive profile character-
ized by low fecundity and extensive investment in each
infant, associated with delayed reproductive maturation,
long gestations, small litters, large neonates, long lacta-
tional periods, and slow postnatal growth (Zimmermann &
Radespiel, 2007). These trends are especially pronounced
in the anthropoids (monkeys, apes, and humans), which
additionally exhibit hemochorial placentation, menstrual
cycles in many species, and emancipation of sexual
behavior from hormonal influences, particularly in females.
The evolutionary basis of these reproductive patterns is not
fully understood but is thought to be associated with
development of primates’ characteristic large brains and
cognitive sophistication (Harvey, Martin, & Clutton-Brock,
1987; Leigh, 2004; Martin, 2007; Zimmermann & Rade-
spiel, 2007).
As reviewed above, many aspects of reproduction have
been studied intensively in a small number of primates. In
contrast, for most of the 637 extant species and sub-
speciesdof which one third to one half are currently
threatened with extinction (Strier, 2007; Rylands, Wil-
liamson, Hoffmann, & Mittermeier, 2008)dlittle or no
systematic information on reproductive physiology is
available. In recent years, however, the development of
noninvasive methods for monitoring reproductive
hormones (e.g., fecal, urinary, and salivary assays) has
begun to greatly expand our knowledge of reproductive
function in a wide range of primates in both captive and
wild settings (Lasley & Savage, 2007). A top priority for
future research on primate reproduction should be to
characterize basic reproductive parameters and processes in
some of the less-studied taxa, such as the tarsiers, pith-
eciines (New World sakis, uakaris, and titi monkeys),
colobines (Old World leaf-eating monkeys), and hylobatids
(gibbons and siamangs). Further, in view of the ubiquity of
environmental instability, in terms of anthropogenic habitat
degradation, global climate change, and, potentially,
exposure to endocrine-disrupting chemicals, it is vital to
deepen our understanding of environmental influences on
reproductive physiology and reproductive behavior in
a variety of primate taxa. Ultimately, both broadening and
deepening our understanding of primate reproductive
function can provide new insights into human reproduction,
will illuminate the evolution of primate life histories, and
may make important contributions to captive management
and conservation efforts.
ABBREVIATIONS
11
b
-HSD 11
b
hydroxysteroid dehydrogenase
ACTH Corticotropin
CG Chorionic gonadotropin
CRF Corticotropin-releasing factor
CRH Corticotropin-releasing hormone
CS Chorionic somatomammotropin
DDE Dichlorodiphenyldichloroethylene
DDT Dichlorodiphenyltrichloroethane
DHEA Dehydroepiandrosterone
DHEA-S Dehydroepiandrosterone sulfate
DHT Dihydrotestosterone
E
1
Estrone
E
2
Estradiol
ER Estrogen receptor
FSH Follicle-stimulating hormone
GABA
g
-aminobutyric acid
GH Growth hormone
GnRH Gonadotropin-releasing hormone
GPR54 G-protein receptor 54
GTH Gonadotropin
HPA Hypothalamicepituitaryeadrenal
HPG Hypothalamicepituitaryegonadal
IGF Insulin-like growth factor
IL Interleukin
IUGR Intrauterine growth restriction
Kp Kisspeptin
LH Luteinizing hormone
MEL Melatonin
NMDA N-methyl-D-aspartate
NPY Neuropeptide Y
OXY Oxytocin
P
4
Progesterone
P450
scc
P450 cholesterol side-chain cleavage
PCB Polycholorinated biphenyl
PCOS Polycystic ovary syndrome
PGF
2a
Prostaglandin F
2a
PR Progesterone receptor
PRL Prolactin
TTestosterone
T
3
Triiodothyronine
T
4
Thyroxine
TGF
b
Transforming growth factor-
b
TSH Thyrotropin
REFERENCES
Abbott, D. H. (1984). Behavioral and physiological suppression of
fertility in subordinate marmoset monkeys. Am. J. Primatol., 6,
169e186.
Abbott, D. H., Digby, L. J., & Saltzman, W. (2009). Reproductive skew in
female marmosets. In R. Hager, & C. B. Jones (Eds.), Reproductive
Skew in Vertebrates. Cambridge University Press.
Alberts, S. C., & Altmann, J. (1995). Preparation and activation: deter-
minants of age at reproductive maturity in male baboons. Behav.
Ecol. Sociobiol., 36, 397e406.
Albrecht, E. D., & Pepe, G. J. (1990). Placental steroid-hormone
biosynthesis in primate pregnancy. Endocr. Rev., 11, 124e150.
Albrecht, E. D., & Pepe, G. J. (1999). Central integrative role of oestrogen in
modulating the communication between the placenta and fetus that
results in primate fetaleplacental development. Placenta, 20,129e139.
319Chapter | 13 Hormones and Reproductive Cycles in Primates
Alvarez, H. P. (2000). Grandmother hypothesis and primate life histories.
Am. J. Phys. Anthropol., 113, 435e450.
AnAge: The Animal Ageing and Longevity Database. (2009). http://
genomics.senescence.info/species/; accessed 05/20/09
Atsalis, S., & Margulis, S. W. (2008a). Primate reproductive aging: from
lemurs to humans. In S. Atsalis, S. W. Margulis, & P. R. Hof (Eds.),
Primate Reproductive Aging: Cross-Taxon Perspectives on Repro-
duction.Interdiscip. Top. Gerontol, 36 (pp. 186e194). Basel,
Switzerland: Karger.
Atsalis, S., & Margulis, S. W. (2008b). Perimenopause and menopause:
documenting life changes in aging female gorillas. In S. Atsalis,
S. W. Margulis, & P. R. Hof (Eds.), Primate Reproductive Aging:
Cross-Taxon Perspectives on Reproduction, Interdiscip. Top. Ger-
ontol, 36 (pp. 119e146). Basel, Switzerland: Karger.
Auchus, R. J., & Rainey, W. E. (2004). Adrenarchedphysiology,
biochemistry and human disease. Clin. Endocrinol., 60, 288e296.
Baird, D. T., Cnattingius, S., Collins, J., Evers, J. L. H., et al. (2006).
Nutrition and reproduction in women. Hum. Reprod. Update, 12,
193e207.
Beach, F. A. (1976). Sexual attractivity, proceptivity, and receptivity in
female mammals. Horm. Behav., 7, 105e138.
Belgorosky, A., Baquedano, M. S., Guercio, G., & Rivarola, M. A. (2008).
Adrenarche: postnatal adrenal zonation and hormonal and metabolic
regulation. Horm. Res., 70, 257e267.
Benirschke, K. (2010). Comparative Placentation. http://placentation.
ucsd.edu/; accessed 06/15/10
Bercovitch, F. B. (1993). Dominance rank and reproductive maturation in
male rhesus macaques (Macaca mulatta). J. Reprod. Fertil., 99,
113e120.
Bercovitch, F. B., & Goy, R. W. (1990). The socioendocrinology of
reproductive development and reproductive success in macaques. In
T. E. Ziegler, & F. B. Bercovitch (Eds.), Socioendocrinology of
Primate Reproduction (pp. 59e93). New York, NY: Wiley-Liss.
Bercovitch, F. B., & Strum, S. C. (1993). Dominance rank, resource
availability, and reproductive maturation in female savanna baboons.
Behav. Ecol. Sociobiol., 33, 313e318.
Bercovitch, F. B., Lebron, M. R., Martinez, H. S., & Kessler, M. J. (1998).
Primigravidity, body weight, and costs of rearing first offspring in
rhesus macaques. Am. J. Primatol., 46, 135e144.
Bergeron, C. (2000). Morphological changes and protein secretion
induced by progesterone in the endometrium during the luteal phase
in preparation for nidation. Human Reprod. 15 Suppl., 1, 119e128.
Bininda-Emonds, O. R. P., Cardillo, M., Jones, K. E., MacPhee, R. D. E.,
Beck, R. M. D., Grenyer, R., et al. (2007). The delayed rise of
present-day mammals. Nature, 446, 507e512, (Corrigendum (2008),
Nature 456, 274.).
Bowman, J. E., & Lee, P. C. (1995). Growth and threshold weaning
weights among captive rhesus macaques. Am J. Phys. Anthropol., 96,
159e175.
Bowman, M. E., Lopata, A., Jaffe, R. B., Golos, T. G., Wickings, J., &
Smith, R. (2001). Corticotropin-releasing hormone-binding protein in
primates. Am. J. Primatol., 53, 123e130.
Brannian, J. D., & Stouffer, R. L. (1991). Progesterone production by
monkey luteal cell subpopulations at different stages of the menstrual
cycle: changes in agonist responsiveness. Biol. Reprod., 44,
141e149.
Bronson, F. H. (1989). Mammalian Reproductive Biology. Chicago, IL:
University of Chicago Press.
Campbell, B. (2006). Adrenarche and the evolution of human life history.
Am. J. Hum. Biol., 18, 569e589.
Campbell, C. J. (2007). Primate sexuality and reproduction. In
C. J. Campbell, A. Fuentes, K. C. MacKinnon, M. Panger, &
S. K. Bearder (Eds.), Primates in Perspective (pp. 423e437). New
York, NY: Oxford University Press.
Caro, T. M., Sellen, D. W., Parish, A., Frank, R., Brown, D. M.,
Voland, E., et al. (1995). Termination of reproduction in nonhuman
and human female primates. Int. J. Primatol., 16, 205e220.
Castellucci, M., De Matteis, R., Meisser, A., Cancello, R., Monsurro, V.,
Islami, D., et al. (2000). Leptin modulates extracellular matrix
molecules and metalloproteinases: possible implications for tropho-
blast invasion. Mol. Human Reprod., 6, 951e958.
Cesario, S. K., & Hughes, L. A. (2007). Precocious puberty: a compre-
hensive review of literature. J. Obstet. Gynecol. Neonatal Nurs., 36,
263e274.
Chardonnens, D., Cameo, P., Aubert, M., Pralong, R., Islami, D.,
Campana, A., et al. (1999). Modulation of human cytotrophoblastic
leptin secretion by interleukin-1aand 17
b
-oestradiol and its effect on
hCG secretion. Mol. Hum. Reprod., 5, 1077e1082.
Charpentier, M. J. E., Tung, J., Altmann, J., & Alberts, S. C. (2008a). Age
at maturity in wild baboons: genetic, environmental and demographic
influences. Molec. Ecol., 17, 2026e2040.
Charpentier, M. J. E., Van Horn, R. C., Altmann, J., & Alberts, S. C.
(2008b). Paternal effects on offspring fitness in a multimale primate
society. Proc. Nat. Acad. Sci. USA, 105, 1988e1992.
Claypool, L. E., Kasuya, E., Saitoh, Y., Marzban, F., & Terasawa, E.
(2000). N-methyl d, l-aspartate induces the release of luteinizing
hormone-releasing hormone in the prepubertal and pubertal female
rhesus monkey as measured by in vivo push-pull perfusion in the
stalk-median eminence. Endocrinology, 141, 219e228.
Coe, C. L., Chen, M., Lowe, E. L., Davidson, J. M., & Levine, S. (1981).
Hormonal and behavioral changes at puberty in the squirrel monkey.
Horm. Behav., 15,36e53.
Consta
ˆncia, M., Hemberger, M., Hughes, J., Dean., W., Ferguson-
Smith, A., Fundele, R., et al. (2002). Placental-specific IGF-II is
a major modulator of placental and fetal growth. Nature, 417,
945e948.
Crespi, B., & Semeniuk, C. (2004). Parenteoffspring conflict in the
evolution of vertebrate reproductive mode. Am. Nat., 163, 635e653.
Crossey, P. A., Pillai, C. C., & Miell, J. P. (2002). Altered placental
development and intrauterine growth restriction in IGF binding
protein-1 transgenic mice. J. Clin. Invest. 110, 411e418.
De Mendoza, A. R., Escobedo, D. E., Davila, I. M., & Saldana, H. B.
(2004). Expansion and divergence of the GH locus between spider
monkey and chimpanzee. Gene, 336, 185e193.
De Roux, N., Genin, E., Carel, J.- C., Matsuda, F., Chaussain, J.eL., &
Milgrom, E. (2003). Hypogonadotropic hypogonadism due to loss of
function of the KiSS1-derived peptide receptor GPR54. Proc. Nat.
Acad. Sci. USA, 100, 10972e10976.
Di Bitetti, M. S., & Janson, C. H. (2000). When will the stork arrive?
Patterns of birth seasonality in neotropical primates. Am. J. Primatol.,
50, 109e130.
Di Fiore, A., & Campbell, C. J. (2007). The Atelines: variation in
ecology, behavior, and social organization. In C. J. Campbell,
A. F. Fuentes, K. C. Mackinnon, M. Panger, & S. Bearder (Eds.),
Primates in Perspective (pp. 155e185). New York, NY: Oxford
University Press.
320 Hormones and Reproduction of Vertebrates
Digby, L. J., Ferrari, S. F., & Saltzman, W. (2007). Callitrichines: the role of
competition in cooperatively breeding species. In C. J. Campbell,
A. F. Fuentes, K. C. Mackinnon, M. Panger, & S. Bearder (Eds.),
Primates in Perspective (pp. 85e106). New York, NY: Oxford
University Press.
Dixson, A. F. (1983). Observations on the evolution and behavioral
significance of “sexual skin” in female primates. Adv. Stud. Behav.,
13,63e106.
Dixson, A. F. (1998). Primate Sexuality: Comparative Studies of the
Prosimians, Monkeys, Apes, and Human Beings. Oxford, UK: Oxford
University Press.
Dixson, A. F., & Nevison, C. M. (1997). The socioendocrinology of
adolescent development in male rhesus monkeys (Macaca mulatta).
Horm. Behav., 31, 126e135.
Duffy, D. M., & Stouffer, R. L. (2003). Luteinizing hormone acts directly
at granulosa cells to stimulate periovulatory processes. Endocrine,
22, 249e256.
Dukelow, W. R. (1985). Reproductive cyclicity and breeding in the
squirrel monkey. In L. A. Rosenblum, & C. L. Coe (Eds.), Handbook
of Squirrel Monkey Research (pp. 169e190). New York, NY: Plenum
Press.
Dunbar, R. I. M. (1977). Age-dependent changes in sexual skin colour and
associated phenomena of female gelada baboons. J. Hum. Evol., 6,
667e672.
Eaton, G. G., Slob, A., & Resko, J. A. (1973). Cycles of mating behav-
iour, oestrogen and progesterone in the thick-tailed bushbaby
(Galago crassicaudatus crassicaudatus) under laboratory conditions.
Anim. Behav., 21, 309e315.
Ebling, F. J. (2005). The neuroendocrine timing of puberty. Reproduction,
129, 675e683.
El Majdoubi, M., Ramaswamy, S., Sahu, A., & Plant, T. M. (2000).
Effects of orchidectomy on levels of the mRNAs encoding gonado-
tropin-releasing hormone and other hypothalamic peptides in the
adult male rhesus monkey (Macaca mulatta). J. Neuroendocrinol.,
12, 167e176.
Ellis, B. J., & Garber, J. (2000). Psychosocial antecedents of variation in
girls’ pubertal timing: maternal depression, stepfather presence, and
marital and family stress. Child Dev., 71, 485e501.
Ellison, P. T., Bribiescas, R. G., Bentley, G. R., Campbell, B. C.,
Lipson, S. F., Panter-Brick, C., et al. (2002). Population variation in
age-related decline in male salivary testosterone. Child Dev., 71,
485e501.
Emanuel, R. L., Robinson, B. G., Seely, E. W., Graves, S. W., Kohane, I.,
Saltzman, D., et al. (1994). Corticotrophin releasing hormone levels
in human plasma and amniotic fluid during gestation. Clin. Endo-
crinol., 40, 257e262.
Emery Thompson, M. (2009). The endocrinology of intersexual rela-
tionships in the apes. In P. T. Ellison, & P. B. Gray (Eds.), Endo-
crinology of Social Relationships. Cambridge, MA.: Harvard
University Press.
Enstam, K. L., & Isbell, L. A. (2007). The guenons (genus Cercopithecus)
and their allies: behavioral ecology of polyspecific associations. In
C. J. Campbell, A. F. Fuentes, K. C. Mackinnon, M. Panger, &
S. Bearder (Eds.), Primates in Perspective (pp. 252e274). New York,
NY: Oxford University Press.
Euling, S. Y., Selevan, S. G., Hirsch Pescovitz, O., & Skakkebaek, N. E.
(2008). Role of environmental factors in the timing of puberty.
Pediatrics, 121, S167eS171.
Fairbanks, L. A., & McGuire, M. T. (1995). Maternal condition and the
quality of maternal care in vervet monkeys. Behaviour, 132, 733e754.
Farage, M., & Maibach, H. (2006). Lifetime changes in the vulva and
vagina. Arch. Gynecol. Obstet., 273, 195e202.
Fashing, P. J. (2007). African colobine monkeys: patterns of between-
group interaction. In C. J. Campbell, A. F. Fuentes, K. C. Mackinnon,
M. Panger, & S. Bearder (Eds.), Primates in Perspective
(pp. 201e224). New York, NY: Oxford University Press.
Fedigan, L. M., & Pavelka, M. S. M. (2007). Reproductive cessation in
female primates. In C. J. Campbell, A. Fuentes, K. C. MacKinnon,
M. Panger, & S. K. Bearder (Eds.), Primates in Perspective
(pp. 437e447). New York, NY: Oxford University Press.
Finn, C. A. (1998). Menstruation: a nonadaptive consequence of uterine
evolution. Q. Rev. Biol., 73, 163e173.
Foerg, R. (1982). Reproduction in Cheirogaleus medius.Folia Primatol.,
39,49e62.
Fowden, A. L. (2003). The insulin-like growth factors and fetoeplacental
growth. Placenta, 24, 803e812.
Freeman, M. E., Kanyicska, B., Lerant, A., & Nagy, G. (2000). Prolactin:
structure, function, and regulation of secretion. Physiol. Rev., 80,
1523e1631.
French, J. A. (1997). Proximate regulation of singular breeding in calli-
trichid primates. In N. G. Solomon, & J. A. French (Eds.), Cooper-
ative Breeding in Mammals (pp. 34e75). New York, NY: Cambridge
University Press.
Furuichi, T., Idani, G., Ihobe, H., Kuroda, S., Kitamura, K., Mori, A., et
al. (1998). Population dynamics of wild bonobos (Pan paniscus)at
Wamba. Int. J. Primatol., 19, 1029e1043.
Gajdos, Z. K. Z., Hirschhorn, J. N., & Palmert, M. R. (2009). What
controls the timing of puberty? An update on progress from genetic
investigation. Curr. Opin. Endocrinol. Diabetes Obes., 16,16e24.
Gicquel, C., & Le Bouc, Y. (2006). Hormonal regulation of fetal growth.
Horm. Res., 65, S28eS33.
Giudice, L. C. (2001). Insulin-like growth factor family in Graafian
follicle development and function. J. Soc. Gynecol. Investig., 8,
S26eS29.
Giudice, L. C. (2006). Application of functional genomics to primate
endometrium: insights into biological processes. Reprod. Biol.
Endocrinol., 4, S4.
Goland, R. S., Wardlaw, S. L., Fortman, J. D., & Stark, R. I. (1992).
Plasma corticotropin releasing factor concentrations in the baboon
during pregnancy. Endocrinol., 131, 1782e1786.
Goldfoot, D. A., Slob, A. K., Scheffler, G., Robinson, J. A.,
Wiegand, S. J., & Cords, J. (1975). Multiple ejaculations during
prolonged sexual tests and lack of resultant serum testosterone
increases in male stumptail macaques (M. arctoides). Arch. Sex.
Behav., 4, 405e420.
Golos, T. G., Durning, M., Fisher, J. M., & Fowler, P. D. (1993). Cloning
of four growth hormone/chorionic somatomammotropin-related
complementary deoxyribonucleic acids differentially expressed
during pregnancy in the rhesus monkey placenta. Endocrinology, 133,
1744e1752.
Gougein, A. (1986). Dynamics of follicular growth in the human: a model
from preliminary results. Hum. Reprod., 1,81e87.
Gould, L., & Sauther, M. (2007). Lemuriformes. In C. J. Campbell,
A. F. Fuentes, K. C. Mackinnon, M. Panger, & S. Bearder (Eds.),
Primates in Perspective (pp. 46e72). New York, NY: Oxford
University Press.
321Chapter | 13 Hormones and Reproductive Cycles in Primates
Graham, C. E. (1979). Reproductive function in aged female chimpan-
zees. Am. J. Phys. Anthropol., 50, 291e300.
Gromoll, J., Wistuba, J., Terwort, N., Godmann, M., Mu
¨ller, T., &
Simoni, M. (2003). A new subclass of the luteinizing hormone/cho-
rionic gonadotropin receptor lacking exon 10 messenger RNA in the
New World monkey (Platyrrhini) lineage. Biol. Reprod., 69,75e80.
Gursky, S. (2007). Tarsiiformes. In C. J. Campbell, A. F. Fuentes,
K. C. Mackinnon, M. Panger, & S. Bearder (Eds.), Primates in
Perspective (pp. 73e85). New York, NY: Oxford University Press.
Haig, D. (1993). Genetic conflicts in human pregnancy. Q. Rev. Biol., 68,
495e532.
Haig, D. (1996). Placental hormones, genomic imprinting and maternal-
fetal communication. J. Evol. Biol., 9, 357e380.
Hardy, M. P., & Schlegel, P. N. (2004). Testosterone production in the
aging male: where does the slowdown occur? Endocrinology, 145,
4439e4440.
Hartwig, W. (2007). Primate evolution. In C. J. Campbell, A. Fuentes,
K. C. MacKinnon, M. Panger, & S. K. Bearder (Eds.), Primates in
Perspective (pp. 11e22). New York, NY: Oxford University Press.
Harvey, P. H., Martin, R. D., & Clutton-Brock, T. H. (1987). Life histories in
comparative perspective. In B. B. Smuts, D. L. Cheney, R. M. Seyfarth,
R.W.Wrangham,&T.T.Struhsaker(Eds.),Primate Societies
(pp. 181e196). Chicago, IL: University of Chicago Press.
Hauguel-De Mouzon, S., Lepercq, J., & Catalano, P. (2006). The known
and unknown of leptin in pregnancy. Am. J. Obstet. Gynecol., 194,
1537e1545.
Havelock, J. C., Auchus, R. J., & Rainey, W. E. (2004). The rise in adrenal
androgen biosynthesis: adrenarche. Semin. Reprod. Med., 22,
337e347.
Hawkes, K. (1997). Hadza women’s time allocation, offspring provi-
sioning, and the evolution of long post-menopausal lifespans. Curr.
Anthropol., 38, 551e578.
Hemingway, C. A., & Bynum, N. (2005). The influence of seasonality on
primate diet and ranging. In D. K. Brockman, & C. P. Van Schaik
(Eds.), Seasonality in Primates: Studies of Living and Extinct Human
and Non-human Primates (pp. 57e104). Cambridge: Cambridge
University Press.
Hendrickx, A. G., & Dukelow, W. R. (1995). Reproductive biology. In
B. T. Bennett, C. R. Abee, & R. Hendickson (Eds.), Nonhuman
Primates in Biomedical Research: Biology and Management
(pp. 147e192). New York, NY: Academic Press.
Henson, M. C., & Castracane, V. D. (2002). Leptin: roles and regulation
in primate pregnancy. Semin. Reprod. Med., 20, 113e122.
Hess, A. P., Nayak, N. R., & Giudice, L. C. (2006). Oviduct and
endometrium: cyclic changes in the primate oviduct and endome-
trium. In J. D. Neill (Ed.) (Third Edition). Knobil and Neill’s
Physiology of Reproduction, Vol. 1 (pp. 337e381). St. Louis, MO:
Elsevier.
Hill, K., & Hurtado, A. M. (1991). The evolution of premature repro-
ductive senescence and menopause in human females: an evaluation
of the ‘grandmother hypothesis. Hum. Nat., 2, 313e350.
Hodgen, G. D., Goodman, A. L., O’Connor, A., & Johnson, D. K. (1977).
Menopause in rhesus monkeys: model for study of disorders in the
human climacteric. Am. J. Obstet. Gynecol., 127, 581e584.
Hull, E. M., Wood, R. I., & McKenna, K. E. (2006). In J. D. Neill (Ed.),
Knobil and Neill’s Physiology of Reproduction (Third Edition).
Neurobiology of male sexual behavior, Vol. 2 (pp. 1729e1824).
St. Louis, MO: Elsevier.
Hutz, R.J., Dierschke, D.J., & Wolf,R. C. (1985). Seasonal effectson ovarian
folliculogenesis in rhesus monkeys. Biol. Reprod., 33,653e659.
Izard, M. K. (1990). Social influences on the reproductive success and
reproductive endocrinology of prosimian primates. In T. E. Ziegler, &
F. B. Bercovitch (Eds.), Socioendocrinology of Primate Reproduction
(pp. 159e186). New York, NY: Wiley-Liss.
Jack, K. M. (2007). The Cebines: toward an explanation of variable social
structure. In C. J. Campbell, A. F. Fuentes, K. C. Mackinnon,
M. Panger, & S. Bearder (Eds.), Primates in Perspective
(pp. 107e123). New York, NY: Oxford University Press.
Jansson, N., Greenwood, S., Johansson, B., Powell, T., & Jansson, T.
(2003). Leptin stimulates the activity of the system A amino acid
transporter in human placental villous fragments. J. Clin. Endocrinol.
Metab., 88, 1205e1211.
Jasienska, G., & Ellison, P. T. (2004). Energetic factors and seasonal
changes in ovarian function in women from rural Poland. Am. J.
Hum. Biol., 16, 563e580.
Johnson, M. H., & Everitt, B. J. (2000). Essential Reproduction. Oxford,
UK: Blackwell Science.
Johnson, S. (2003). Life history and competitive environment: trajectories
of growth, maturation and reproductive output among chacma
baboons. Am. J. Phys. Anthropol., 120,83e98.
Jolly, C. J. (2007). Baboons, mandrills, and mangabeys: Afro-Papionin
socioecology in a phylogenetic perspective. In C. J. Campbell,
A. F. Fuentes, K. C. Mackinnon, M. Panger, & S. Bearder (Eds.),
Primates in Perspective (pp. 240e251). New York, NY: Oxford
University Press.
Kaplowitz, P. B. (2008). Link between body fat and the timing of puberty.
Pediatrics, 121, S208eS217.
Keen, K. L., Wegner, F. H., Bloom, S. R., Ghatei, M. A., & Terasawa, E.
(2008). An increase in kisspeptin-54 release occurs with the pubertal
increase in luteinizing hormone-releasing hormone-1 release in the
stalk-median eminence of female rhesus monkeys in vivo.Endocri-
nology, 149, 4151e4157.
King, B. R., Smith, R., & Nicholson, R. C. (2002). Novel glucocorticoid
and cAMP interactions on the CRH gene promoter. Mol. Cell.
Endocrinol., 194,19e28.
Kingsley, S. (1982). Causes of non-breeding and the development of the
secondary sexual characteristics in the male orangutan: a hormonal
study. In L. E. M. De Boer (Ed.), The Orangutan: Its Biology and
Conservation(pp. 215e229). The Hague, The Netherland: Junk
Publishers, Dr. W.
Kirkpatrick, R. C. (2007). The Asian colobines. In C. J. Campbell,
A. F. Fuentes, K. C. Mackinnon, M. Panger, & S. Bearder (Eds.),
Primates in Perspective (pp. 186e200). New York, NY: Oxford
University Press.
Kliman, H. J., Nestler, J. E., Sermasi, E., Sanger, J. M., & Strauss, J. F.
(1986). Purification, characterization, and in vitro differentiation of
cytotrophoblasts from human term placentae. Endocrinology, 118,
1567e1582.
Kuehl, T. J., & Dukelow, W. R. (1975). Ovulation induction during the
anovulatory season in Saimiri sciureus.J. Med. Primatol., 4,23e31.
Kuzawa, C. W. (1998). Adipose tissue in human infancy and childhood:
an evolutionary perspective. Am. J. Phys. Anthropol. Suppl., 27,
177e209.
Lacroix, M., -C., Guibourdenche, J., Frendo, J., -L., Muller, F., & Evain-
Brion, D. (2002). Human placental growth hormoneda review.
Placenta, 23, S87eS94.
322 Hormones and Reproduction of Vertebrates
Lasley, B. L., & Savage, A. (2007). Advances in the understanding of
primate reproductive endocrinology. In C. J. Campbell, A. Fuentes,
K. C. MacKinnon, M. Panger, & S. K. Bearder (Eds.), Primates in
Perspective (pp. 356e369). New York, NY: Oxford University Press.
Lee, K. Y., & De Mayo, F. J. (2004). Animal models of implantation.
Reproduction, 128, 679e695.
Lee, P. C., Majluf, P., & Gordon, I. J. (1991). Growth, weaning and
maternal investment from a comparative perspective. J. Zool., 225,
99e114.
Leigh, S. R. (2004). Brain growth, life history, and cognition in primate
and human evolution. Am. J. Primatol., 62, 139e164.
Lewis, M. P., Morlese, J. F., Sullivan, M. H., & Elder, M. G. (1993).
Evidence for deciduaetrophoblast interactions in early human preg-
nancy. Hum. Reprod., 8, 965e968.
Li, Y., Ye, C., Shi, P., Zou, X.- J., Xiao, R., Gong, Y.- Y., & Zhang, Y.- P.
(2005). Independent origin of the growth hormone gene family in
New World monkeys and Old World monkeys/hominoids. J. Mol.
Endocrinol., 35, 399e409.
Lockwood, C. J., Krikun, G., Hausknecht, V., Want, E.-Y., & Schatz, F.
(1997). Decidual cell regulation of hemostasis during implantation
and menstruation. Ann. NY Acad. Sci., 828, 188e193.
Luckett, W. P. (1974). Comparative development and evolution of the
placenta in primates. In W. P. Luckett (Ed.), Contributions to
Primatology: The Reproductive Biology of the Primates
(pp. 142e234). Basel, Switzerland: Karger.
Luckhaus, J., & Ferrin, M. (1989). Effects of intraventricular oxytocin
infusion on LH and cortisol secretion in ovariectomized rhesus
monkeys. Acta Endocrinol., 120(suppl.1), 59.
Luetjens, C. M., Weinbauer, G. F., & Wistuba, J. (2005). Primate sper-
matogenesis: new insights into comparative testicular organization,
spermatogenic efficiency and endocrine control. Biol. Rev., 80,
475e488.
Maggioncalda, A. N., Czekala, N. M., & Sapolsky, R. M. (2002). Male
orangutan subadulthood: a new twist on the relationship between chronic
stress and developmental arrest. Am. J. Phys. Anthro., 118,25e32.
Maggioncalda, A. N., Sapolsky, R. M., & Czekala, N. M. (1999).
Reproductive hormone profiles in captive male orangutans: implica-
tions for understanding developmental arrest. Am. J. Phys. Anthro.,
109,19e32.
Malpaux, B. (2006). Seasonal regulation of reproduction in mammals. In
J. D. Neill. Knobil and Neill’s Physiology of Reproduction (Ed.)
(Third Edition)., Vol. 2 (pp. 2231e2281). St. Louis, MO: Elsevier.
Maneckjee, R., Srinath, B. R., & Moudgal, N. R. (1976). Prolactin
suppresses release of luteinising hormone during lactation in the
monkey. Nature, 262, 507e508.
Mann, D. R., Akinbami, M. A., Gould, K. G., Paul, K.,& Wallen, K. (1998).
Sexual maturation in male rhesus monkeys: importance of neonatal
testosterone exposure and social rank. J. Endocrinol., 156, 493e501.
Martin, R. D. (2007). The evolution of human reproduction: a primato-
logical perspective. Yearb. Phys. Anthropol., 50,59e84.
McLachlan, R. I., O’Donnell, L., Meachem, S. J., Stanton, P. G., De
Kretser, D. M., Pratis, K., et al. (2002a). Hormonal regulation of
spermatogenesis in primates and man: insights for development of the
male hormonal contraceptive. J. Androl., 23, 149e162.
McLachlan, R. I., O’Donnell, L., Meachem, S. J., Stanton, P. G., De
Kretser, D. M., Pratis, K., et al. (2002b). Identification of specific
sites of hormonal regulation in spermatogenesis in rats, monkeys, and
man. Rec. Prog. Horm. Res., 57, 149e179.
McNeilly, A. S. (1994). Suckling and the control of gonadotropin
secretion. In E. Knobil, & J. D. Neill (Eds.) (2
nd
Ed.). Vol. 2 The
Physiology of Reproduction, (pp. 1179e1212) New York, NY: Raven
Press.
McNeilly, A. S. (2001). Lactational control of reproduction. Reprod.
Fertil. Dev., 13, 583e590.
McNeilly, A. S., Abbott, D. H., Lunn, S. F., Chambers, P. C., &
Hearn, J. P. (1981). Plasma prolactin concentrations during the
ovarian cycle and lactation and their relationship to return of fertility
post partum in the common marmoset (Callithrix jacchus). J. Reprod.
Fertil., 62, 353e360.
McNulty, W. P., Novy, M. J., & Walsh, S. W. (1981). Fetal and postnatal
development of the adrenal glands in Macaca mulatta.Biol. Reprod.,
25, 1079e1089.
Mendoza, S. P., Coe, C. L., Lowe, E. L., & Levine, S. (1979). The
physiological response to group formation in adult male squirrel
monkeys. Psychoneuroendocrinology, 3, 221e229.
Mesiano, S., & Jaffe, R. B. (1997). Developmental and functional biology
of the primate fetal adrenal cortex. Endocr. Rev., 18, 378e403.
Messinis, I. E. (2006). Ovarian feedback, mechanism of action and
possible clinical implications. Hum. Reprod. Update, 12,
557e571.
Milligan, L. A., Gibson, S. V., Williams, L. E., & Power, M. L. (2008).
The composition of milk from Bolivian squirrel monkeys (Saimiri
boliviensis boliviensis). Am. J. Primatol., 70,35e43.
Milton, K. (1985). Mating patterns of woolly spider monkeys, Brachyteles
arachnoides: implications for female choice. Behav. Ecol. Sociobiol.,
17,53e59.
Mizuno, M., & Terasawa, E. (2005). Search for neural substrates medi-
ating inhibitory effects of oestrogen on pulsatile luteinising
hormone-releasing hormone release in vivo in ovariectomized female
rhesus monkeys (Macaca mulatta). J. Neuroendocrinol., 17,
238e245.
Mossman, H. W. (1987). Vertebrate Fetal Membranes. New Brunswick,
NJ: Rutgers University Press.
Mu
¨ller, T., Gromoll, J., Simula, A. P., Norman, R., Sandhowe-
Klaverkamp, R., & Simoni, M. (2004a). The carboxyterminal peptide
of chorionic gonadotropin facilitates activation of the marmoset LH
receptor. Exp. Clin. Endocrinol. Diabetes, 112, 574e579.
Mu
¨ller, T., Simoni, M., Pekel, E., Luetjens, C. M., Chandolia, R.,
Amato, F., et al. (2004b). Chorionic gonadotrophin beta subunit
mRNA but not luteinising hormone beta subunit mRNA is expressed
in the pituitary of the common marmoset (Callithrix jacchus). J. Mol.
Endocrinol., 32,115e128.
Musicki, B., Pepe, G. J., & Albrecht, E. D. (1997). Functional differen-
tiation of placental syncytiotrophoblasts during baboon pregnancy:
developmental expression of chorionic somatomammotropin
messenger ribonucleic acid and protein levels. J. Clin. Endocrinol.
Metab., 85, 4105e4110.
Nakano, R. (1997). Control of the luteal function in humans. Semin.
Reprod. Endocrinol., 15, 335e344.
Nasir-ud-Din, Hoessli, D. C., Rungger-Bra
¨ndle, E., Hussain, S. A., &
Walker-Nasir, E. (2003). Role of sialic acid and sulfate groups in
cervical mucus physiological functions: study of Macaca radiata
glycoproteins. Biochim. Biophys. Acta, 1623,53e61.
Nebesio, T. D., & Eugster, E. A. (2007). Current concepts in normal and
abnormal puberty. Curr. Probl. Pediatr. Adolesc. Health Care, 37,
50e72.
323Chapter | 13 Hormones and Reproductive Cycles in Primates
Nekaris, A., & Bearder, S. K. (2007). The Lorisiform primates of Asia
and mainland Africa. In C. J. Campbell, A. F. Fuentes,
K. C. Mackinnon, M. Panger, & S. Bearder (Eds.), Primates in
Perspective (pp. 24e45). New York, NY: Oxford University Press.
Neville, M. C. (2001). Anatomy and physiology of lactation. Pediatr.
Clin. North Am., 48,13e34.
Nguyen, A. D., & Conley, A. J. (2008). Adrenal androgens in humans and
nonhuman primates: production, zonation and regulation. Endocr.
Dev., 13,33e54.
Niswender, G. D., & Nett, T. M. (1994). Corpus luteum and its control in
infraprimate species. In E. Knobil, & J. D. Neill (Eds.), The Physi-
ology of Reproduction (pp. 781e816). New York, NY: Raven Press.
Norconk,M. A. (2007). Sakis, uakaris, and titi monkeys: behavioral diversity
in a radiation of primate seedpredators. In C. J. Campbell, A. F. Fuentes,
K. C. Mackinnon, M. Panger, & S. Bearder (Eds.), Primates in
Per sp ect iv e (pp. 123e138). New York, NY: Oxford University Press.
Novy, M. J., Aubert, M. L., Kaplan, S. L., & Grumbach, M. M. (1981).
Regulation of placental growth and chorionic somatomammotropin in
the rhesus monkey: effects of protein deprivation, fetal anencephaly,
and placental vessel ligation. Am. J. Obstet. Gynecol., 140, 552e562.
O’Byrne, K. T., Lunn, S. F., & Coen, C. W. (1990). Central oxytocin
stimulates luteinizing hormone release in the marmoset, a primate
which fails to show lactationally-induced infertility. J. Neuro-
endocrinol., 2, 419e421.
Oftedal, O. T. (1984). Milk composition, milk yield and energy output at
peak lactation: a comparative review. Symp. Zool. Soc. Lond., 51,
33e85.
Ogren, L., & Talamantes, F. (1994). The placenta as an endocrine organ:
polypeptides. In E. Knobil, & J. D. Neill (Eds.), The Physiology of
Reproduction (2nd ed.). (pp. 875e945) New York, NY: Raven Press.
Peccei, J. S. (2001a). A critique of the grandmother hypothesis: old and
new. Am. J. Hum. Biol., 13, 434e452.
Peccei, J. S. (2001b). Menopause: adaptation or epiphenomenon? Evol.
Anthropol., 10,43e57.
Pepe, G. J., & Albrecht, E. D. (1990). Regulation of the primate fetal
adrenal-cortex. Endocr. Rev., 11, 151e176.
Perret, M. (1986). Social influences on oestrous cycle length and plasma
progesterone concentrations in the female lesser mouse lemur
(Microcebus murinus). J. Reprod. Fertil., 77, 303e311.
Perret, M. (1992). Environmental and social determinants of sexual
function in the male lesser mouse lemur (Microcebus murinus). Folia
Primatol., 59,1e25.
Perret, M., & Schilling, A. (1995). Sexual responses to urinary chemo-
signals depend on photoperiod in a male primate. Physiol. Behav., 58,
633e639.
Petraglia, F., Florio, P., Nappi, C., & Genazzani, A. R. (1996). Peptide
signaling in human placenta and membranes: autocrine, paracrine,
and endocrine mechanisms. Endocr. Rev., 17, 156e186.
Petraglia, F., Florio, P., & Vale, W. (2005). Placental expression of
neurohormones and other neuroactive molecules in human preg-
nancy. In M. L. Power, & J. Schulkin (Eds.), Birth, Distress and
Disease (pp. 16e73). Cambridge, UK: Cambridge University Press.
Plant, T. M., & Marshall, G. R. (2001). The functional significance of
FSH in spermatogenesis and the control of its secretion in male
primates. Endocr. Rev., 22, 764e786.
Plant, T. M., & Ramaswamy, S. (2009). Kisspeptin and the regulation of
the hypothalamicepituitaryegonadal axis in the rhesus monkey
(Macaca mulatta). Peptides, 30,67e75.
Plant, T. M., & Witchel, S. F. (2006). Puberty in nonhuman primates and
humans. In J. D. Neill (Ed.), Knobil and Neill’s Physiology of
Reproduction (Third Edition)., Vol. 2 (pp. 2177e2230). St. Louis,
MO: Elsevier.
Plant, T. M., Gay, V. L., Marshall, G. R., & Arslan, M. (1989). Puberty in
monkeys is triggered by chemical stimulation of the hypothalamus.
Proc. Nat. Acad. Sci. USA, 86, 2506e2510.
Plant, T. M., Ramaswamy, S., & Dipietro, M. J. (2006). Repetitive acti-
vation of hypothalamic G protein-coupled receptor 54 with intrave-
nous pulses of kisspeptin in the juvenile monkey (Macaca mulatta)
elicits a sustained train of gonadotropin-releasing hormone
discharges. Endocrinology, 147, 1007e1013.
Poonia, B., Walter, L., Dufour, J., Harrison, R., Marx, P. A., &
Veazey, R. S. (2006). Cyclic changes in the vaginal epithelium of
normal rhesus macaques. J. Endocrinol., 190, 829e835.
Power, M. L., & Tardif, S. D. (2005). Maternal nutrition and metabolic
control of pregnancy. In M. L. Power, & J. Schulkin (Eds.), Birth,
Distress and Disease (pp. 88e113). Cambridge, UK: Cambridge
University Press.
Power, M. L., Bowman, M. E., Smith, R., Ziegler, T. E., Layne, D. G.,
Schulkin, J., et al. (2006). The pattern of maternal serum cortico-
tropin-releasing hormone concentration during pregnancy in the
common marmoset (Callithrix jacchus). Am. J. Primatol., 68,
181e188.
Power, M. L., Oftedal, O. T., & Tardif, S. D. (2002). Does the milk of
Callitrichid monkeys differ from that of larger anthropoids? Am. J.
Primatol., 56, 117e127.
Preti, G., Wysocki, C. J., Barnhart, K. T., Sondheimer, S. J., &
Leyden, J. J. (2003). Male axillary extracts contain pheromones that
affect pulsatile secretion of luteinizing hormone and mood in women
recipients. Biol. Reprod., 68, 2107e2113.
Profet, M. (1993). Menstruation as a defense against pathogens trans-
ported by sperm. Q. Rev. Biol., 68, 335e386.
Randolph, J. F., Jr. (2008). The endocrinology of the reproductive years.
J. Sex. Med., 5, 2274e2281.
Rasweiler, J. J., IV, & De Bonilla, H. (1992). Menstruation in short-tailed
fruit bats (Carollia spp.). J. Reprod. Fertil., 95, 231e248.
Richard, A. F. (1987). Malagasy prosimians: female dominance. In
B. B. Smuts, D. L. Cheney, R. M. Seyfarth, R. W. Wrangham, &
T. T. Struhsaker (Eds.), Primate Societies (pp. 25e33). Chicago, IL:
University of Chicago Press.
Roa, J., Aguilar, E., Dieguez, C., Pinilla, L., & Tena-Sempere, M. (2008).
New frontiers in kisspeptin/GPR54 physiology as fundamental gate-
keepers of reproductive function. Front. Neuroendocrinol., 29,48e69.
Roh, C. R., Budhara, V., Kim, H. S., Nelson, D. M., & Sadovsky, Y.
(2005). Microarray-based identification of differentially expressed
genes in hypoxic term human trophoblasts and in placental villi of
pregnancies with growth restricted fetuses. Placenta, 26, 319e328.
Rowe, N. (1996). The Pictorial Guide to the Living Primates. Charles-
town, RI: Pogonias Press.
Rutherford, J. N. (2009). Fetal signaling through placental structure and
endocrine function: illustrations and implications from a nonhuman
primate model. Am. J. Hum. Biol., 21, 745e753.
Rutherford, J. N., & Tardif, S. D. (2008). Placental efficiency and intra-
uterine resource allocation strategies in the common marmoset
pregnancy. Am. J. Phys. Anthropol., 137,60e68.
Rutherford, J. N., & Tardif, S. D. (2009). Developmental plasticity of the
microscopic placental architecture in relation to litter size variation in
324 Hormones and Reproduction of Vertebrates
the common marmoset monkey (Callithrix jacchus). Placenta, 30,
105e110.
Rylands, A. B., Williamson, E. A., Hoffmann, M., & Mittermeier, R. A.
(2008). Primate surveys and conservation assessments. Oryx, 42,
313e314.
Saltzman, W., Digby, L. J., & Abbott, D. H. (2009). Reproductive skew in
female common marmosets: what can proximate mechanisms tell us
about ultimate causes? Proc. Biol. Sci., 276, 389e399.
Savini, T., Boesch, C., & Reichard, U. H. (2008). Home-range charac-
teristics and the influence of seasonality on female reproduction in
white-handed gibbons (Hylobates lar) at Khao Yai National Park,
Thailand. Am. J. Phys. Anthropol., 135,1e12.
Scammell, J. G., Funkhouser, J. D., Moyer, F. S., Gibson, S. V., &
Willis, D. L. (2008). Molecular cloning of pituitary glycoprotein a-
subunit and folicle stimulating hormone and chorionic gonadotropin
b
-subnits from New World squirrel monkey and owl monkey. Gen.
Comp. Endocrinol., 155, 534e541.
Schallenberger, E., Richardson, D. W., & Knobil, E. (1981). Role of
prolactin in the lactational amenorrhoea of the rhesus monkey
(Macaca mulatta). Biol. Reprod., 25, 370e374.
Schiml, P. A., Mendoza, S. P., Saltzman, W., Lyons, D. M., & Mason, W. A.
(1996). Seasonality in squirrel monkeys (Saimiri sciureus): social
facilitation by females. Physiol. Behav., 60, 1105e1113.
Schiml, P. A., Mendoza, S. P., Saltzman, W., Lyons, D. M., & Mason, W. A.
(1999). Annual physiological changes in individially housed squirrel
monkeys (Saimiri sciureus). Am. J. Primatol., 47,93e103.
Schlabritz-Loutsevitch, N. E., Dudley, C. J., Gomez, J. J.,
Nevill, C. H., Smith, B. K., Jenkins, S. L., et al. (2007). Meta-
bolic adjustments to moderate maternal nutrient restriction. Br. J.
Nutr., 98, 276e284.
Schoeters, G., Den Hond, E., Dhooge, W., Van Larebeke, N., & Leijs, M.
(2008). Endocrine disruptors and abnormalities of pubertal develop-
ment. Basic Clin. Pharmacol. Toxicol., 102, 168e175.
Schramm, R. D., Paprocki, A. M., & Bavister, B. D. (2002). Features
associated with reproductive ageing in female rhesus monkeys. Hum.
Reprod., 17, 1597e1603.
Schuler, L. A., & Kessler, M. A. (1992). Bovine placental prolactin-
related hormones. Trends Endocrinol. Metab., 3, 334e338.
Schurgin, S., Canavan, B., Koutkia, P., Depaoli, A. M., & Grinspoon, S.
(2004). Endocrine and metabolic effects of physiologic r-metHu-
Leptin administration during acute caloric deprivation in normal-
weight women. J. Clin. Endocrinol. Metab., 89, 5402e5409.
Schwartz, S. M., Wilson, M. E., Walker, M. L., & Collins, D. C. (1985).
Social and growth correlates of puberty onset in female rhesus
monkeys. Nutr. Behav., 2, 225e232.
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R.,
Acierno, J. S., Jr., Shagoury, J. K., et al. (2003). The GPR54 gene as
a regulator of puberty. N. Engl. J. Med., 349, 1614e1627.
Setchell, J. M. (2003). The evolution of alternative reproductive morphs
in male primates. In C. B. Jones (Ed.), Sexual Selection and Repro-
ductive Competition in Primates: New Perspectives and Directions
(pp. 413e435). Norman, OK: American Society of Primatologists.
Setchell, J. M., & Dixson, A. F. (2002). Developmental variables and
dominance rank in adolescent male mandrills (Mandrillus sphinx).
Am. J. Primatol., 56,9e25.
Shibata,M.,Friedman,R.L.,Ramaswamy,S.,&Plant,T.M.
(2007). Evidence that down regulation of hypothalamic KiSS-1
expression is involved in the negative feedback action of
testosterone to regulate luteinising hormone secretion in the
adult male rhesus monkey (Macaca mulatta). J. Neuro-
endocrinol., 19,43
2e438.
Shideler, S. E., Gee, N. A., Chen, J., & Lasley, B. L. (2001). Estrogen and
progestogen metabolites and follicle-stimulating hormone in the aged
macaque female. Biol. Reprod., 65, 1718e1725.
Shinohara, K., Morofushi, M., Funabashi, T., & Kimura, F. (2001).
Axillary pheromones modulate pulsatile LH secretion in humans.
Neuroreport, 12, 893e895.
Shively, C., Clarke, S., King, N., Schapiro, S., & Mitchell, G. (1982).
Patterns of sexual behavior in male macaques. Am. J. Primatol., 2,
373e384.
Skangalis, M., Swenson, C. E., Mahoney, C. J., & O’Leary, W. M. (1979).
The normal microbial flora of the baboon vagina. J. Med. Primatol.,
8, 289e297.
Smith, R. J., & Jungers, W. L. (1997). Body mass in comparative
primatology. J. Hum. Evol., 32, 523e559.
Smith, R., Chan, E. C., Bowman, M. E., Harewood, W. J., &
Phippard, A. F. (1993). Corticotropin releasing hormone in baboon
pregnancy. J. Clin. Endocrinol. Metab., 76, 1063e1068.
Smith,R., Mesiano, S., Nicholson, R., Clifton, V., Zakar, T., Chan, E.-C.,et al.
(2005). The regulation of human parturition. In M. L. Power, &
J. Schulkin (Eds.), Birth, Distress and Disease (pp. 74e87). Cambridge,
UK: Cambridge University Press.
Smith, R., Wickings, J., & Bowman, M. B. (1999). Corticotropin-
releasing hormone in chimpanzee and gorilla pregnancy. J. Clin.
Endocrinol. Metab., 84, 2820e2825.
Smucny, D. A., Abbott, D. H., Mansfield, K. G., Schultz-Darken, N. J.,
Yamamoto, M. E., Alencar, A. I., et al. (2004). Reproductive output,
maternal age and survivorship in captive common marmoset females
(Callithrix jacchus). Am. J. Primatol., 64, 107e121.
Soares, M. J. (2004). The prolactin and growth hormone families: preg-
nancy-specific hormones/cytokines at the maternalefetal interface.
Reprod. Biol. Endocrinol., 2, 51.
Soares, M. J., & Linzer, D. I. H. (2001). The rodent prolactin family and
pregnancy. In N. D. Horseman (Ed.), Prolactin (pp. 139e167).
Norwell, MA: Kluwer Academic Publishers.
Sofikitis, N., Giotitsas, N., Tsounapi, P., Baltogiannis, D., Giannakis, D.,
& Pardalidis, N. (2008). Hormonal regulation of spermatogenesis and
spermiogenesis. J. Steroid. Biochem. Mol. Biol., 109, 323e330.
Soini, P. (1988). The pygmy marmoset, genus Cebuella.In
R. A. Mittermeier, A. B. Rylands, A. F. Coimbra-Filho, & G. A. B. da
Fonseca (Eds.), Ecology and Behavior of Neotropical Primates, Vol. 2
(pp. 79e129). Washington, DC: World Wildlife Fund.
Solomon, S. (1994). The primate placenta as an endocrine organ: steroids.
In E. Knobil, & J. D. Neill (Eds.), The Physiology of Reproduction
(2nd ed.). (pp. 863e873) New York, NY: Raven Press.
Stammbach, E. (1987). Desert, forest and montane baboons: multilevel
societies. In B. B. Smuts, D. L. Cheney, R. M. Seyfarth,
R. W. Wrangham, & T. T. Struhsaker (Eds.), Primate Societies
(pp. 112e120). Chicago, IL: University of Chicago Press.
Stern, K., & McClintock, M. K. (1998). Regulation of ovulation by
human pheromones. Nature, 392, 177e179.
Stouffer, R. L., Xu, F., & Duffy, D. M. (2007). Molecular control of
ovulation and luteinization in the primate follicle. Front. Biosci., 12,
297e307.
Strassmann, B. I. (1996). The evolution of endometrial cycles and
menstruation. Q. Rev. Biol., 71, 181e220.
325Chapter | 13 Hormones and Reproductive Cycles in Primates
Strier, K. B. (2007). Conservation. In C. J. Campbell, A. Fuentes,
K. C. MacKinnon, M. Panger, & S. K. Bearder (Eds.), Primates in
Perspective (pp. 496e509). New York, NY: Oxford University Press.
Strier, K. B., & Ziegler, T. E. (1994). Insights into ovarian function in wild
muriqui monkeys (Brachyteles arachnoides). Am. J. Primatol., 32,
31e40.
Struhsaker, T. T., & Leland, L. (1987). Colobines: infanticide by adult
males. In B. B. Smuts, D. L. Cheney, R. M. Seyfarth,
R. W. Wrangham, & T. T. Struhsaker (Eds.), Primate Societies
(pp. 83e97). Chicago, IL: University of Chicago Press.
Stumpf, R. (2007). Chimpanzees and bonobos: diversity within and
between species. In C. J. Campbell, A. F. Fuentes, K. C. Mackinnon,
M. Panger, & S. Bearder (Eds.), Primates in Perspective
(pp. 321e344). New York, NY: Oxford University Press.
Suarez, S. S., & Pacey, A. A. (2006). Sperm transport in the female
reproductive tract. Hum. Reprod. Update, 12,23e37.
Tardif, S. D. (1985). Histologic evidence for age-related differences in
ovarian function in tamarins (Saguinus sp; Primates). Biol. Reprod.,
33, 993e1000.
Tardif, S. D., & Ross, C. N. (2009). Integration of proximate and
evolutionary explanation of reproductive strategy: the case of calli-
trichid primates and implications for human biology. Am. J. Hum.
Biol., 21, 731e738.
Tardif, S. D., & Ziegler, T. E. (1992). Features of reproductive senescence
in tamarins (Saguinus spp.), a New World primate. J. Reprod. Fertil.,
94, 411e421.
Tardif, S. D., Araujo, A., Arruda, A., French, J. A., Sousa, M. B. C., &
Yamamoto, M. E. (2008). Reproduction and aging in marmosets and
tamarins. In S. Atsalis, S. W. Margulis, & P. R. Hof (Eds.), Primate
Reproductive Aging: Cross-Taxon Perspectives on Reproduction,
Interdiscip. Top. Gerontol., 36 (pp. 29e48). Basel, Switzerland:
Karger.
Tardif, S. D., Power, M., Oftedal, O. T., Power, R. A., & Layne, D. G.
(2001). Lactation, maternal behavior and infant growth in common
marmoset monkeys: effects of maternal size and litter size. Behav.
Ecol. Sociobiol., 51,17e25.
Tardif, S. D., Ziegler, T. E., Power, M., & Layne, D. G. (2005). Endocrine
changes in full-term pregnancies and pregnancy loss due to energy
restriction in the common marmoset (Callithrix jacchus). J. Clin.
Endocrinol. Metab., 90, 335e339.
Tardif, S., Power, M., Layne, D., Smucny, D., & Ziegler, T. (2004). Energy
restriction initiated at different gestational ages has varying effects on
maternal weight gain and pregnancy outcome in common marmoset
monkeys (Callithrix jacchus). Br. J. Nutr., 92,841e849.
Tay, C. C. K., Glasier, A. F., & McNeilly, A. S. (1996). Twenty-four hour
patterns of prolactin secretion during lactation ad the relationship to
suckling and the resumption of fertility in breast-feeding women.
Hum. Reprod., 11, 950e955.
Tena-Sempere, M. (2007). Roles of ghrelin and leptin in the control of
reproductive function. Neuroendocrinology, 86, 229e241.
Tena-Sempere, M. (2008). Ghrelin as a pleotrophic modulator of gonadal
function and and reproduction. Nat. Clin. Pract. Endocrinol. Metab.,
4, 666e674.
Terasawa, E. (2001). Luteinizing hormone-releasing hormone (LHRH)
neurons: mechanisms of pulsatile LHRH release. Vitam. Horm., 63,
91e129.
Terasawa, E. (2005). Role of GABA in the mechanism of the onset of
puberty in non-human primates. Int. Rev. Neurobiol., 71, 113e129.
Thierry, B. (2007). The macaques: a double-layered social organization.
In C. J. Campbell, A. F. Fuentes, K. C. Mackinnon, M. Panger, &
S. Bearder (Eds.), Primates in Perspective (pp. 224e239). New York,
NY: Oxford University Press.
Tilbrook, A. J., & Clarke, I. J. (2001). Negative feedback regulation of the
secretion and actions of gonadotropin-releasing hormone in males.
Biol. Reprod., 64, 735e742.
Utami, S. S. (2000). Bimaturism in Orang-Utan males: Reproductive and
Ecological Strategies. Ph.D. dissertation. Universiteit Utrecht.
Utami, S. S., Goossens, B., Bruford, M. W., De Ruiter, J. R., & Van
Hooff, J. A. R. A. M. (2002). Male bimaturism and reproductive
success in Sumatran orang-utans. Behav. Ecol., 13, 643e652.
Valeggia, C. R., Mendoza, S. P., Fernandez-Duque, E., Mason, W. A., &
Lasley, B. (1999). Reproductive biology of female titi monkeys
(Callicebus moloch). Am. J. Primatol., 47, 183e195.
Van Horn, R. N., & Eaton, G. R. (1979). Reproductive physiology and
behavior in prosimians. In G. A. Doyle, & R. D. Martin (Eds.), The
Study of Prosimmian Behavior (pp. 79e122). New York, NY:
Academic Press.
Van Schaik, C. P., & Brockman, D. K. (2005). Seasonality in primate
ecology, reproduction and life history: an overview. In
D. K. Brockman, & C. P. Van Schaik (Eds.), Seasonality in Primates:
Studies of Living and Extinct Human and Non-human Primates
(pp. 3e20). New York, NY: Cambridge University Press.
Videan, E. N., Fritz, J., Heward, C. B., & Murphy, J. (2008). Reproductive
aging in chimpanzees (Pan troglodytes). In S. Atsalis, S. W. Margulis,
& P. R. Hof (Eds.), Primate Reproductive Aging: Cross-Taxon
Perspectives on Reproduction.Interdiscip. Top. Gerontol, 36
(pp. 103e118). Basel, Switzerland: Karger.
Vitzthum, V. J., Thornburg, J., & Spielvogel, H. (2009). Seasonal
modulation of reproductive effort during early pregnancy in humans.
Am. J. Hum. Biol., 21, 548e558.
Vom Saal, F. S., Finch, C. E., & Nelson, J. F. (1994). Natural history and
mechanisms of reproductive aging in humans, laboratory rodents, and
other selected vertebrates. In E. Knobil, & J. D. Neill (Eds.), The
Physiology of Reproduction, (2nd ed.). (pp. 1213e1314). NY: Raven
Press.
Vullie
´moz, N. R., Xiao, E. N., Xia-Zhang, L. N., Rivier, J., & Ferin, M.
(2008). Astressin B, a nonselective corticotropin-releasing hormone
receptor antagonist, prevents the inhibitory effect of ghrelin on
luteinizing hormone pulse frequency in the ovariectomized rhesus
monkey. Endocrinology, 149, 869e874.
Vullie
´moz, N. R., Xiao, E., Xia-Zhang, L. N., Germond, M., Rivier, J., &
Ferin, M. (2004). Decrease in luteinizing hormone pulse frequency
during a five-hour peripheral ghrelin infusion in the ovariectomized
rhesus monkey. J. Clin. Endocrinol. Metab., 89, 5718e5723.
Wade, G. N., Schneider, J. E., & Li, H. Y. (1996). Control of fertility by
metabolic cues. Am. J. Physiol., 33,E1eE19.
Walker, W. H., Fitzpatrick, S. L., Barrera-Saldana, H. A., Resendez-
Perez, D., & Saunders, G. F. (1991). The human placental lactogen
genes: structure, function, evolution and transcription regulation.
Endocr. Rev., 12, 316e328.
Wallen, K. (1990). Desire and ability: hormones and the regulation of
female sexual behavior. Neurosci. Biobehav. Rev., 14, 233e241.
Wallen, K. (2005). Hormonal influences on sexually differentiated
behavior in nonhuman primates. Front. Neuroendocrinol., 26,7e26.
Wallen, K., & Zehr, J. L. (2004). Hormones and history: the evolution and
development of primate female sexuality. J. Sex Res., 41, 101e112.
326 Hormones and Reproduction of Vertebrates
Wallis, O. C., & Wallis, M. (2002). Characterisation of the GH gene
cluster in a new-world monkey, the marmoset (Callithrix jacchus).
J. Mol. Endocrinol., 29,89e97.
Wang, R. Y., Needham, L. L., & Barr, D. B. (2005). Effects of environ-
mental agents on the attainment of puberty: considerations when
assessing exposure to environmental chemicals in the National
Children’s Study. Environ. Health Perspect., 113, 1100e1107.
Wang, Z., Liang, B., Racey, P. A., Wang, Y.-L., & Zhang, S.-Y. (2008).
Sperm storage, delayed ovulation, and menstruation of the female
Rickett’s big-footed bat (Myotis ricketti). Zool. Stud., 47, 215e221.
Wasser, S. K., & Barash, D. P. (1983). Reproductive suppression among
female mammals: implications for biomedicine and sexual selection
theory. Q. Rev. Biol., 58m, 513e538.
Wasser, S. K., Norton, G. W., Kleindorfer, S., & Rhine, R. J. (2004).
Population trend alters the effects of maternal dominance rank on
lifetime reproductive success in yellow baboons (Papio cyn-
ocephalus). Behav. Ecol. Sociobiol., 56, 338e345.
Watanabe, G., & Terasawa, E. (1989). In vivo release of luteinizing
hormone releasing hormone increases with puberty in the female
rhesus monkey. Endocrinology, 125,92e99.
Watanobe, H. (2002). Leptin directly acts within the hypothalamus to
stimulate gonadotropin-releasing hormone secretion in vivo in rats.
J. Physiol., 545, 255e268.
Watts, D. P. (1998). Seasonality in the ecology and life histories of
mountain gorillas (Gorilla gorilla beringei). Int. J. Primatol., 19,
929e948.
Wehrenberg, W. B., & Dyrenfurth, I. (1983). Photoperiod and ovulatory
menstrual cycles in female macaque monkeys. J. Reprod. Fertil., 68,
119e122.
Weiss, G., Butler, W. R., Dierschke, D. J., & Knobil, E. (1976). Influence
of suckling on gonadotropin secretion in the postpartum rhesus
monkey. Proc. Soc. Exp. Biol. Med., 153, 330e331.
Weller, L., & Weller, A. (1993). Human menstrual synchrony: a critical
assessment. Neurosci. Biobehav. Rev., 17, 427e439.
Wickings, E. J., & Nieschlag, E. (1980). Seasonality in endocrine and
exocrine testicular function of the adult rhesus monkey (Macaca
mulatta) maintained in a controlled laboratory environment. Int. J.
Androl., 3,87e104.
Wickings, E. J., Marshall, G. R., & Nieschlag, E. (1986). Endocrine
regulation of male reproduction. In W. R. Dukelow, & J. Erwin
(Eds.), Comparative Primate Biology (pp. 149e170). New York, NY:
Alan R. Liss.
Wiebe, R. H., Williams, L. E., Abee, C. R., Yeoman, R. R., &
Diamond, E. J. (1988). Seasonal changes in serum dehydroepian-
drosterone, androstenedione and testosterone levels in the squirrel
monkey (Saimiri bolivensis bolivensis). Am.J.Primatol.,14,285e291.
Wildman, D. E., Chen, C., Erez, O., Grossman, L. I., Goodman, M., &
Romero, R. (2006). Evolution of the mammalian placenta revealed by
phylogenetic analysis. Proc. Nat. Acad. Sci., 103, 3203e3208.
Wilson, M. E., & Gordon, T. P. (1989a). Season determines timing of first
ovulation in rhesus monkeys (Macaca mulatta) housed outdoors.
J. Reprod. Fertil., 85, 583e591.
Wilson, M. E., & Gordon, T. P. (1989b). Short-day melatonin pattern
advances puberty in seasonally breeding rhesus monkeys (Macaca
mulatta). J. Reprod. Fertil., 86, 435e444.
Wilson, M. E., Gordon, T. P., & Collins, D. C. (1986). Ontogeny of
luteinizing hormone secretion and first ovulation in seasonal breeding
rhesus monkeys. Endocrinology, 118, 293e301.
Wise, P. M. (2006). Aging of the female reproductive system. In
E. J. Masoro, & S. N. Austad (Eds.), Handbook of the Biology of
Aging (pp. 570e590). London, UK: Elsevier.
Wistuba, J., Schrod, A., Greve, B., Hodges, J. K., Aslam, H.,
Weinbauer, G. F., et al. (2003). Organization of seminiferous
epithelium in primates: relationship to spermatogenic efficiency,
phylogeny, and mating system. Biol. Reprod., 69, 582e591.
Witkin, S. S., Linhares, A. M., & Giraldo, P. (2007). Bacterial flora of the
female genital tract: function and immune regulation. Best Pract. Res.
Clin. Obstet. Gynaecol., 21, 347e354.
Wright, P., King, S. J., Baden, A., & Jernvall, J. (2008). Aging in wild
female lemurs: sustained fertility with increased infant mortality. In
S. Atsalis, S. W. Margulis, & P. R. Hof (Eds.), Primate Reproductive
Aging: Cross-Taxon Perspectives on Reproduction Interdiscip. Top.
Gertonol., 36 (pp. 17e28). Basel, Switzerland: Karger.
Yeoman, R. R., Wegner, F. H., Gibson, S. V., Williams, L. E.,
Abbott, D. H., & Abee, C. R. (2000). Midcycle and luteal elevations
of follicle stimulating hormone in squirrel monkeys (Saimiri boli-
viensis) during the estrous cycle. Am. J. Primatol., 52, 207e211.
Yoder, A. D., Rasoloarison, R. M., Goodman, S. M., Irwin, J. A.,
Atsalis, S., Ravosa, M. J., et al. (2000). Remarkable species diversity
in Malagasy mouse lemurs (primates, Microcebus). Proc. Nat. Acad.
Sci., 97, 11325e11330.
Zehr, J. L., Van Meter, P. E., & Wallen, K. (2005). Factors regulating the
timing of puberty onset in female rhesus monkeys (Macaca mulatta):
role of prenatal androgens, social rank, and adolescent body weight.
Biol. Reprod., 72, 1087e1094.
Zeleznik, A. J., & Benyo, D. F. (1994). Control of follicular development,
corpus luteum function and the recognition of pregnancy in higher
primates. In E. Knobil, & J. D. Neill (Eds.), The Physiology of
Reproduction (2
nd
Edition)., Vol. 2 (pp. 751e782). New York, NY:
Raven Press.
Zeleznik, A. J., & Pohl, C. R. (2006). Control of follicular development,
corpus luteum function, the maternal recognition of pregnancy, and
the neuroendocrine regulation of the menstrual cycle in higher
primates. In J. D. Neill (Ed.), Knobil and Neill’s Physiology of
Reproduction (Third Edition)., Vol. 2 (pp. 2449e2510). St. Louis,
MO: Elsevier.
Zhang, X., Zhu, C., Lin, H., Yang, Q., Ou, Q., Li, Y., et al. (2007). Wild
fulvous fruit bats (Rousettus leschenaulti) exhibit human-like
menstrual cycle. Biol. Reprod., 77, 358e364.
Ziegler, T. E., Strier, K. B., & Van Belle, S. (2009). The reproductive
ecology of South American primates: ecological adaptations in
ovulation and conception. In P. A. Garber, A. Estrada, J. C. Bicca-
Marques, E. W. Heymann, & K. B. Strier (Eds.), South American
Primates: Comparative Perspectives in the Study of Behavior,
Ecology, and Conservation (pp. 191e210). New York, NY:
Springer.
Zimmermann, E., & Radespiel, U. (2007). Primate life histories. In
W. Henke, & I. Tattersall (Eds.), Handbook of Paleoanthropology
Vol. 2: Primate Evolution and Human Origins (pp. 1163e1205). New
York, NY: Springer-Verlag.
327Chapter | 13 Hormones and Reproductive Cycles in Primates
