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A transverse section (100 pm) through the spinal cord of a male rat at segment L5. The motor neurones forming the spinal nucleus of bulbocavernosus (SNB) are indicated. Stained
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Newborn female Albino Swiss rats received testosterone propionate, dihydrotestosterone benzoate or oestradiol benzoate for 4 days after birth. The neonatal administration of all three hormones maintained neurones of the spinal nucleus of bulbocavernosus (SNB) complex in adulthood at levels intermediate between those found in normal females (approxi...
Citations
... By contrast, in the SNB, treatment of females with EB completely fails to alter cell number from the normal feminine pattern (Figure 1) (Breedlove et al., 1982; Breedlove, 1997). Similarly, SNB motoneuron number is not affected in males treated postnatally with the aromatase inhibitor 4-OH-androstenedione (Currie et al., 1990). The findings in Tfm rats, and the failure of estrogens to prevent SNB motoneuron death, suggests that the sparing of both the SNB and its target musculature specifically requires activation of the androgen receptor. ...
Cell number in the spinal nucleus of the bulbocavernosus (SNB) of rats was the first neural sex difference shown to differentiate under the control of androgens, acting via classical intracellular androgen receptors. SNB motoneurons reside in the lumbar spinal cord and innervate striated muscles involved in copulation, including the bulbocavernosus (BC) and levator ani (LA). SNB cells are much larger and more numerous in males than in females, and the BC/LA target muscles are reduced or absent in females. The relative simplicity of this neuromuscular system has allowed for considerable progress in pinpointing sites of hormone action, and identifying the cellular bases for androgenic effects. It is now clear that androgens act at virtually every level of the SNB system, in development and throughout adult life. In this review we focus on effects of androgens on developmental cell death of SNB motoneurons and BC/LA muscles; the establishment and maintenance of SNB motoneuron soma size and dendritic length; BC/LA muscle morphology and physiology; and behaviors controlled by the SNB system. We also describe new data on neurotherapeutic effects of androgens on SNB motoneurons after injury in adulthood.
... By contrast, in both the SNB and DLN, treatment of females with estradiol benzoate completely fails to alter cell number from the normal feminine pattern [15,55,9] (Fig. 1). Similarly, SNB motoneuron number is not affected in males treated postnatally with the aromatase inhibitor 4-OH-androstenedione [24], indicating that conversion of testosterone to an estrogen is not necessary for the development of a masculine number of motoneurons in this system. The findings in Tfm rats, and the failure of estrogens to prevent SNB motoneuron death, suggests that the sparing of both the SNB and its target musculature specifically requires activation of the androgen receptor. ...
... n both sexes up to birth, and (3) that perinatal androgen administration to females increases (while androgen suppression in males decreases) adult SNB neuron numbers ( Breedlove, 1984). The same general characteristics are also true of Albino Swiss rats, although there appear to be strain differences regarding (1) which hormones are effective (cf. Currie et al. 1990; Breedlove et al. 1982), (2) whether androgens can maintain neurons in the absence of muscles or vice versa (cf. Davidson et al. 1990). Studies with Sprague-Dawley rats suggest that SNB motor neurons may initially form a common population with the related DLN group (Sengelaub & Arnold, 1986) and, if so, the development of the SNB cannot ...
... Ltd, Fancy Road, Poole, Dorset, BH 17 7NH) on the last 4 days of pregnancy (n = 10). This androgen has previously been shown to be particularly effective in maintaining the relevant neurons in the Albino Swiss strain (Currie et al. 1990). A second group consisted of pups which received DHTB (200 ,tg, s.c.) on days 1-4 after birth, but had received no prenatal exposure (n = 9). ...
... All animals were killed with an overdose of sodium pentobarbitone, and perfused with mammalian Ringer solution with lignocaine followed by 500 ml buffered 10 % formaldehyde. The perineal muscles, if present, were dissected out and weighed together with the phallus; these muscles consisted of levator ani, bulbocavernosus and ischiocavernosus (for description, see Venable, 1966; McKenna & Nadelhaft, 1986; Currie et al. 1990). The lower part of the spinal cord was removed and stored in buffered 10 % formaldehyde before sectioning at 100 ,um on a Bio-rad microcut H 1200 vibratome and staining with 0-4% thionin in alcohol and acetic acid (pH 4 5). ...
Motor neuron groups in the L5-S1 region of the spinal cord were examined in male and female Albino Swiss rats and in females treated with 5 alpha-dihydrotestosterone benzoate (DHTB) either prenatally or postnatally. The spinal nucleus of bulbocavernosus (SNB) contained some five times more neurons in males than females. Perinatal DHTB treatment to females increased SNB numbers; prenatal treatment was less effective than postnatal. Within the same part of the cord, males possessed more motor neurons in the dorsolateral nucleus (DLN) than females. Perinatal DHTB treatment to females (both prenatal and postnatal) increased DLN neuron numbers. The perineal muscles (the normal target for SNB and DLN motor neurons) are absent in adult female rats; they are maintained by postnatal (but not prenatal) DHTB treatment. Two other motor neurons groups within the same region of cord, the retrodorsolateral nucleus (RDLN) and the ventromedial nucleus (VM) show no sex differences and are not affected by perinatal androgen treatment.
... For example, pre-or post-natal exposure to testosterone maintains the SNB complex in Sprague-Dawley rats, while dihydrotestosterone is less effective (and is only effective when administered post-natally) and oestradiol is without effect (Breedlove et ai, 1982; Hall et ai, 1987; Sengelaub et ai, 1989). In Albino Swiss rats, post-natal dihydrotestoster¬ one administration is very effective at maintaining SNB neurone numbers, while testosterone and oestradiol are (a) equipotent and (b) somewhat less effective (Currie et ai, 1990). ...
... The present experiments also confirm that the administration of androgens to females during the perinatal period results in the maintenance of higher numbers of SNB neurones than in control females. Currie et ai (1990) have demonstrated that 5a-dihydrotestosterone was effective in main¬ taining SNB neurones in Albino Swiss rats, although sexual dimorphisms within the brain appear to require aromatizable androgens for masculinization (e.g. Arnold & Gorski, 1984; Tobet et ai, 1986). ...
... In a previous study with Albino Swiss rats (Currie et ai, 1990), post-natal oestradiol treatment maintained SNB neurone numbers in the absence of perineal muscles. How¬ ever, retrograde labelling studies are still needed for Albino Swiss rats in order to confirm which motor neurones innervate particular perineal muscles. ...
Female Albino Swiss rats were exposed to 5 alpha-dihydrotestosterone benzoate (DHTB) for the last 4 days of gestation, or for 4 days after birth, or both. Post-natal DHTB exposure (as well as pre-plus post-natal exposure) resulted in a 2-3-fold increase in the number of motor neurones forming the spinal nucleus of bulbocavernosus (SNB); numbers were intermediate between those found in normal females (approximately 40) and males (approximately 200). These DHTB-treated groups also possessed perineal muscles which were approximately 25% of the weight of those in normal males. Transverse sections of one of the muscles (levator ani) showed that it had approximately half the muscle fibres of normal males. Females exposed prenatally to DHTB showed a small (but significant) rise in SNB numbers, but had no recognizable perineal muscles.
Androgens have a variety of protective and therapeutic effects in both the central and peripheral nervous systems. Here we review these effects as they related specifically to spinal and cranial motoneurons. Early in development, androgens are critical for the formation of important neuromuscular sex differences, decreasing the magnitude of normally occurring cell death in select motoneuron populations. Throughout the lifespan, androgens also protect against motoneuron death caused by axonal injury. Surviving motoneurons also display regressive changes to their neurites as a result of both direct axonal injury and loss of neighboring motoneurons. Androgen treatment enhances the ability of motoneurons to recover from these regressive changes and regenerate both axons and dendrites, restoring normal neuromuscular function. Androgens exert these protective effects by acting through a variety of molecular pathways. Recent work has begun to examine how androgen treatment can interact with other treatment strategies in promoting recovery from motoneuron injury.
The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic motor nucleus in the rat lumbar spinal cord. SNB motoneurons and their perineal target muscles are present in adult males, but reduced or absent in adult females. This dimorphism is due to the presence of androgens during development. Perinatal treatment of females with testosterone (T), or a combination of dihydrotestosterone (DHT) and estrogen (E + D females) from embryonic (E) day 16 through postnatal (P) day 5, results in a masculine number of SNB motoneurons and the retention of the target muscles. Perinatal treatment with estrogen alone does not masculinize the SNB; prenatal treatment with DHT alone from E17–E22 results in a feminine number of SNB motoneurons and a significantly altered motoneuron morphology and connectivity. To determine if masculinization of the SNB involves the interaction of estrogen and DHT or results from a longer exposure to DHT alone, the number, morphology, and connectivity of SNB motoneurons in females treated with DHT both pre‐ and post‐natally (from E16–P5) were examined.
At E22, DHTP (E16–P5) females have SNB motoneuron numbers identical to E+D and normal females, but far fewer than normal males, thus indicating that T is essential for prenatal masculinization. After E22, SNB motoneuron number declines precipitously in normal females but remains stable in DHTP (E16–P5) females and E+D females, which do not differ from normal males at P10. These results demonstrate that DHT can completely masculinize SNB motoneuron number without any synergistic actions with estrogen, and suggest that the development of SNB motoneuron number is strictly an androgen‐mediated event.
In adulthood, horseradish peroxidase histochemistry reveals that the connectivity, dendritic length, and soma size of SNB motoneurons in DHTP (E17–P5) females are identical to those of normal males but differ significantly from those of DHTP (E17–E22) females. These data suggest that the altered connectivity in DHTP (E17–E22) females is not simply a hormone‐specific effect, but the result of a truncated hormone exposure. Thus, DHT can fully masculinize SNB morphology and connectivity if given during the appropriate period of development. It is suggested that while T may be required to masculinize the SNB prenatally, DHT may be involved in masculinizing postnatal aspects of SNB development. © 1992 Wiley‐Liss, Inc.
Serotonin (5-HT) may act during development as a neurotrophic agent. Evidence suggests that sexually dimorphic regions of the mammalian nervous system (which often possess sexually dimorphic patterns of 5-HT innervation) could provide a model for this aspect of 5-HT action. Albino Swiss rat pups were treated with p-chlorophenyl alanine (pCPA, 200 mg/kg) or 5-hydroxytryptophan (5-HTP, 75 mg/kg) for 14 days after birth. As adults, the number of motor neurons in the sexually dimorphic spinal nucleus of bulbocavernosus (SNB) and dorsolateral nucleus (DLN), together with the non-dimorphic ventromedial nucleus (VM) were analysed. Postnatal treatment with 5-HTP had a general effect of increasing motor neuron numbers in all three groups. However, pCPA treatment had a marked and specific effect on SNB neuron numbers, increasing these in both sexes (+250% in females and +60% in males) compared with control animals. The results suggest that the postnatal innervation of ventral horn motor neurons by 5-HT-containing terminals may affect cell death at this time.
Previous studies have shown that (i) androgen administration and (ii) depletion of serotonin can independently masculinise parts of the medial preoptic area and groups of motor neurons in the lumbosacral spinal cord when applied during the early postnatal period. We report here that these two control mechanisms interact in the neonatal female rat. Serotonin depletion by p-chlorophenyl alanine extends the 'critical period' during which androgens can act to stabilise neuron numbers within two sexually dimorphic motor neuron groups in segments L5-S1 (the spinal nucleus of bulbocavernosus and the dorsolateral nucleus), probably by slowing the rate of naturally occurring cell death. A non-dimorphic group of motor neurons (the ventromedial nucleus) was unaffected.
In Syrian hamsters, reproductive behaviors are initiated in the presence of appropriate hormonal and chemosensory cues. These cues are detected and integrated within a highly conserved pathway that converges on a small nuclear group in the lateral aspect of the medial preoptic area, the magnocellular subdivision of the medial preoptic nucleus (MPN mag). The MPN mag plays a critical role in the regulation of male mating behavior--bilateral ablation of the MPN mag eliminates copulation. The MPN mag is sexually differentiated in both neuron number and density, but not in overall volume or volume of individual neurons. The current study used unbiased stereological methods to determine when the MPN mag becomes sexually differentiated. Our data indicate that the MPN mag becomes sexually dimorphic in volume and cell number after the critical period when steroid treatment induces male sexual behavior.
