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I ncrease in serum concentration of TSH (ng/ml: mean ± SEM) lOmin after i.v. injection of TRH (850 ng/lOOg body weight) at different stages of the estrous cycle. Stars indicate that values are significantly different from the proestrous level (* p <0.01: ** p<0.001).

I ncrease in serum concentration of TSH (ng/ml: mean ± SEM) lOmin after i.v. injection of TRH (850 ng/lOOg body weight) at different stages of the estrous cycle. Stars indicate that values are significantly different from the proestrous level (* p <0.01: ** p<0.001).

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Serum TSH, LH and FSH were measured at various times during the day, during the estrous cycle of the rat. Proestrous surges of FSH and LH were detected as previously reported. TSH values fell to low levels in the late afternoon on each day of the cycle. There was a significant elevation of TSH at 13.00 h on both proestrus and estrus. The elevation...

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... obtained after TRH injection on the different days of the cycle. This in­ crease was already present 2 min after the injection of the neurohormone and reached maximum values at 10 min af­ ter the injection. The response at 10 min after TRH injection was maximal on proestrus and decreased progressively to minimal values on diestrus II (p<0.01) (fig. 4). The response was decreased further by ovariectomy (p<0.001). Estrogen treatment returned the response of ovariectomized rats to diestrous II values. ...

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Serum prolactin (Prl) was measured following decapitation at various stages of the estrous cycle in control animals and following cervicovaginal stimulation with a glass rod. Serum Prl was low at 10.00 h at all stages of the estrous cycle but was elevated on the afternoon of proestrus with peak values at 16.00 h and on the afternoon of estrus with...

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... However, it remains unclear whether TRH is physiologically functional, as PRL secretion during proestrus is normal in TRH-knockout mice [12]. Moreover, only a 20% increase in blood thyroid-stimulating hormone (TSH) concentration was observed during the proestrus afternoon in rats [13]. Thus, there remains considerable uncertainty as to whether TRH in proestrus activates TSH-producing cell thyrotrophs to stimulate TSH secretion. ...
... reported that blood TSH levels increased by only approximately 20% between 10:00 and 13:00 h and then decreased by approximately 50% until 19:00 h in proestrus rats [13]. Moreover, shorter handling (40 s of cervical stimulation) at 10:00 h diminished these changes in TSH secretion. ...
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The secretion of several hypothalamic peptide hormones is activated during the preovulatory period. Hypothalamic thyrotropin-releasing hormone (TRH) is one such hormone with reproductive and/or metabolic significance. However, it remains unclear whether thyroid-stimulating hormone (TSH)-producing thyrotrophs are produced during the preovulatory period. We previously found a transient increase in the expression of the nuclear receptor NR4A3, a well-known immediate early gene, in the proestrus afternoon in the anterior pituitary glands of rats. To investigate the relationship between TRH secretion and pituitary NR4A3 expression during proestrus, we used proestrus and thyroidectomized rats to identify NR4A3-expressing cells and examined the regulation of Nr4a3 gene expression via the hypothalamus-pituitary-thyroid (HPT) axis. The percentage of NR4A3-expressing cells increased in thyrotrophs at 14:00 h of proestrus. Incubation of rat primary pituitary cells with TRH transiently stimulated Nr4a3 expression. Thyroidectomy to attenuate the negative feedback effects led to increased serum TSH levels and Nr4a3 gene expression in the anterior pituitary, whereas thyroxine (T4) administration conversely suppressed Nr4a3 expression. Additionally, the administration of T4 or TRH antibodies significantly suppressed the increase in Nr4a3 expression at 14:00 h of proestrus. These results demonstrate that pituitary NR4A3 expression is regulated by the HPT axis, and that TRH stimulates thyrotrophs and induces NR4A3 expression during the proestrus afternoon. This suggests the potential involvement of NR4A3 in the regulation of the HPT axis during pre- and post-ovulatory periods.
... Trh expression in hypothalamus is high in the later diestrus phase, tends to decrease during proestrus and early estrus (34). Serum T4 and T3 concentrations increase during proestrus (35). Thiouracilinduced hypothyroid-female rats have irregular estrous cycles after 16 days of treatment, they show a prolonged diestrus phase, lower serum estradiol but higher progesterone concentrations during proestrus compared to the same phase in euthyroid rats and a peak of serum T3 and of T4 concentrations at proestrus (36). ...
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The hypothalamus-pituitary-thyroid-axis (HPT) is one of the main neuroendocrine axes that control energy expenditure. The activity of hypophysiotropic thyrotropin releasing hormone (TRH) neurons is modulated by nutritional status, energy demands and stress, all of which are sex dependent. Sex dimorphism has been associated with sex steroids whose concentration vary along the life-span, but also to sex chromosomes that define not only sexual characteristics but the expression of relevant genes. In this review we describe sex differences in basal HPT axis activity and in its response to stress and to metabolic challenges in experimental animals at different stages of development, as well as some of the limited information available on humans. Literature review was accomplished by searching in Pubmed under the following words: “sex dimorphic” or “sex differences” or “female” or “women” and “thyrotropin” or “thyroid hormones” or “deiodinases” and “energy homeostasis” or “stress”. The most representative articles were discussed, and to reduce the number of references, selected reviews were cited.
... There are studies suggesting that sex hormones affect TSH levels in blood of animals (Castro-Vazquez et al., 1981;Chen, 1984;Donda et al., 1987;Farbota et al., 1987;Borges et al., 1998;Lu et al., 1998;Banu and Aruldhas, 2002). Nevertheless, studies concerning the effect of sex hormones on TSH cell numbers (Dada et al., 1984;Ibrahim et al., 1986) and localizations (Goldman et al., 1988-89) are rather limited. ...
... Different studies examined the effects of sex hormones on TSH level (Castro-Vazquez et al., 1981;Chen, 1984;Donda et al., 1987;Farbota et al., 1987;Borges et al., 1998;Lu et al., 1998;Banu and Aruldhas, 2002). It was reported that estrogen stimulates TSH secretion in females (Banu and Aruldhas, 2002). ...
Article
The aim of the present study was to investigate histochemically the localization of thyroid-stimulating hormone (TSH) cells and the number of TSH cells in adenohypophysis of ovariectomized adult females, intact females at estrous and diestrous phase of sexual cycles and castrated and non-castrated adult male rats. TSH cells, distributed throughout the pars distalis in all groups, were observed more frequent in areas near to the pars intermedia than other regions. The cells were round, ovoid, stellar-shaped and had contacts with sinusoids. Their nuclei were large and round-shaped. The cells were found mostly single or occasionally in groups of double and triple. The number of TSH cells was higher in estrous than diestrous phase in intact rats. In adenohypophysis of ovariectomized rats, their numbers were less than that of intacts in estrous, but higher than that of found in diestrous phases. Furthermore, the numbers of TSH cells in intact females during estrous phase was higher than those found in intact and castrated male rats. On the other hand, castration reduced the number of TSH cells while ovariectomy had no effect in this respect.
... The in vitro assay also showed a stimulatory effect of MPA treatment on basal and TRH-induced TSH release from the pituitaries of adult OVX rats. We (14) and others (3,15,16) had shown that the decreased TSH response to TRH of OVX rats was restored by estrogen treatment. We also had reported before (5) a stimulatory effect of testosterone given chronically to castrated male rats on in vitro basal and TRH-stimulated TSH release. ...
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Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0. 25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro.
... Other authors have shown that estradiol administration to ovariectomized rats recovered the reduced TSH response to TRH of the castrated animals (1,16). However, this stimulatory effect was not found by Christianson et al. (2), even though they employed similar doses of EB (0.33 µg/100 g body weight for 10 days and 0.25 µg/100 g body weight for 7 days). ...
... Chen and Walfish (3,4), employing a dose similar to the intermediary EB dose of the present study (2 µg/ 100 g body weight for 7 days), also found a stimulatory effect of estrogen on the TSH response to TRH. Therefore, our in vitro data are in agreement with those obtained in in vivo studies (1,16) and support the concept that estradiol is physiologically important to maintain the normal response to TRH in females. The induction of increasing num- 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 bers of TRH receptors in the pituitary gland (1) seems to be the mechanism by which estrogen stimulates the TSH response to TRH. ...
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We studied the basal and thyrotropin-releasing hormone (TRH) (50 nM) induced thyrotropin (TSH) release in isolated hemipituitaries of ovariectomized rats treated with near-physiological or high doses of 17-beta-estradiol benzoate (EB; sc, daily for 10 days) or with vehicle (untreated control rats, OVX). One group was sham-operated (normal control). The anterior pituitary glands were incubated in Krebs-Ringer bicarbonate medium, pH 7.4, at 37 degrees C in an atmosphere of 95% O2/5% CO2. Medium and pituitary TSH was measured by specific RIA (NIDDK-RP-3). Ovariectomy induced a decrease (P < 0.05) in basal TSH release (normal control = 44.1 +/- 7.2; OVX = 14.7 +/- 3.0 ng/ml) and tended to reduce TRH-stimulated TSH release (normal control = 33.0 +/- 8.1; OVX = 16.6 +/- 2.4 ng/ml). The lowest dose of EB (0.7 microgram/100 g body weight) did not reverse this alteration, but markedly increased the pituitary TSH content (0.6 +/- 0.06 microgram/hemipituitary; P < 0.05) above that of OVX (0.4 +/- 0.03 microgram/hemipituitary) and normal rats (0.46 +/- 0.03 microgram/hemipituitary). The intermediate EB dose (1.4 micrograms/100 g body weight) induced a nonsignificant tendency to a higher TSH response to TRH compared to OVX and a lower response compared to normal rats. Conversely, in the rats treated with the highest dose (14 micrograms/100 g body weight), serum 17-beta-estradiol was 17 times higher than normal, and the basal and TRH-stimulated TSH release, as well as the pituitary TSH content, was significantly (P < 0.05) reduced compared to normal rats and tended to be even lower than the values observed for the vehicle-treated OVX group, suggesting an inhibitory effect of hyperestrogenism. In conclusion, while reinforcing the concept of a positive physiological regulatory role of estradiol on the TSH response to TRH and on the pituitary stores of the hormone, the present results suggest an inhibitory effect of high levels of estrogen on these responses.
... The elevated levels of TSH observed during the beginning of the luteal phase in our sheep are to some extent comparable to the changes in TSH concentrations found during the cycle of the rat (Castro-Vazquez et al., 1981;Miller et al., 1977). Those authors explained the elevated TSH concentrations during proestrus and estrus in the rat by a long-lasting action of estradiol on the pituitary. ...
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In order to define the patterns of TSH, T4, T3, rT3, GH and cortisol during the estrous cycle of sheep, pluriparous and primiparous ewes were synchronized with progestagen-impregnated pessaries (Veramix) at the start of the normal breeding season. After the pessaries were removed (day 0), daily blood sampling was carried out in cannulated ewes during the ovulatory cycle. Hormonal analyses of TSH, T4, T3, rT3, GH, cortisol, LH and progesterone (P) were performed by RIA. P and LH levels during the cycle were conform to the literature and were not different between the primiparous and pluriparous ewes of different breeds used in this study. Neither age nor breed influenced the hormone patterns. A significant negative correlation was found between TSH and P during the cycle, although the correlation between P and T4 was not significant; during the estrous period, low P levels were paralleled by high T4 levels, whereas the reverse was observed during the luteal phase. Higher T3 levels and T3/T4 ratios were observed during the luteal phase. No obvious pattern of rT3 and cortisol during the cycle was found. The GH concentration increased during the 17 days of the cycle. A positive correlation with P was calculated. During the estrous cycle obvious changes in thyroid hormones, GH and TSH occurred. However, this study shows no causal relationship between the thyroid and the gonadal axes.
... Furthermore, there is also evidence to suggest an action of progesterone on the pelvic nerve and/or the neural centers which are activated by stimulation of its sensory field (the cervix and the vagina, Ref. 22). For instance, brain-pituitary responsiveness to cervicovaginal stimulation varies during the estrous cycle, presumably as a consequence of changes in the ovarian output of estrogen and progesterone (12,(28)(29). Several reports also indicate that progesterone facilitates the bursts of PRL secretion that continue for days after cervicovaginal stimulation (30)(31)(32)(33)(34). ...
Article
Single stimulations of the vagina and cervix were performed between proestrus and the first day of diestrus with a stimulator designed to grade the intravaginal penetration of a rod. The percent incidence of pseudopregnancy after this stimulation was exponentially related to the extent of intravaginal penetration and was also affected by the stage of the cycle at which the stimulation was performed. At 10.00 h on proestrus, an exponential increase in the incidence of pseudopregnancy was observed with shallow penetrations, while an exponential decrease was found when deeper penetrations were applied. Such negative exponential correlation had disappeared at 22.00 h on proestrus. At that time, also, some responses were elicited by very shallow penetrations (17 mm) and all the animals responded to penetrations of 20 mm or more. Sensitivity to cervicovaginal stimulation at 10.00 h on estrus was lower than that at 22.00 h on proestrus and it was even lower at 10.00 h on the first day of diestrus. The response to 18 mm of penetration was studied every 3 h between 10.00 h on proestrus and 10.00 h on estrus, and then every 12 h until 10.00 h on the first day of diestrus. This stimulation was usually ineffective to induce pseudopregnancy, except for a brief period encompassing the night between proestrus and estrus, when a peak in the incidence of responses was reached. This peak sensitivity could be advanced following the s.c. administration of 250 and 500 ng of LH-RH at 11.00 h on proestrus. Other doses were ineffective. The peptide (500 ng) was unable to induce pseudopregnancy in rats that received no cervicovaginal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
... Furthermore, there is also evidence to suggest an action of progesterone on the pelvic nerve and/or the neural centers which are activated by stimulation of its sensory field (the cervix and the vagina, Ref. 22). For instance, brain-pituitary responsiveness to cervicovaginal stimulation varies during the estrous cycle, presumably as a consequence of changes in the ovarian output of estrogen and progesterone (12,(28)(29). Several reports also indicate that progesterone facilitates the bursts of PRL secretion that continue for days after cervicovaginal stimulation (30)(31)(32)(33)(34). ...
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The sensory mechanisms that participate in the induction of pseudopregnancy after a single injection of progesterone were investigated. Unless otherwise indicated, rats were kept in group cages and vaginal smears were taken daily. Progesterone evoked pseudopregnancy in a dose-dependent manner when administered to proestrous or estrous rats that received no cervicovaginal stimulation. The probability of pseudopregnancy after progesterone was higher on estrus. Cervicovaginal stimulation of proestrous rats that received 5 mg progesterone 10 h before was performed with a rod with a sliding stop attached to regulate its intravaginal penetration. Progesterone facilitated responsiveness to this stimulus, although the amount injected was not significantly effective in increasing the incidence of pseudopregnancy in nonstimulated rats. However, the mere application of the stop of the stimulator on the perineal skin was followed by a significantly higher incidence of pseudopregnancy in progesterone-injected rats than in their vehicle-injected controls, which suggested an action of the steroid on perineal sensitivity. Accordingly, the pseudopregnancy-evoking effect of progesterone was clearly inhibited by refraining from taking vaginal smears for 5 days after steroid injection on estrus. No further inhibition was observed after isolating the animals in single rat cages. However, daily finger stimulation of the perineal skin of nonsmeared rats restored to a normal level response to progesterone. Furthermore, this response was severely impaired by transecting the pudendal nerves before the injection. It is concluded that pseudopregnancy is induced in progesterone-treated rats through sensory stimulation of the pudendal receptive field and it is suggested that the pudendal nerve may subserve as a secondary afferent system to elicit the pseudopregnancy response. The possibility progesterone also acts on other afferent systems including the main afferent system constituted by the pelvic nerve is discussed.
Article
I. Introduction IN THE RAT, the corpus luteum is formed on the morning of estrus in response to the surge of luteinizing hormone released on the previous day, proestrus. However, unlike other mammals whose corpora lutea secrete increasing amounts of progesterone for several days (1), the newly formed corpora lutea of the rat secrete progesterone for only 2 days after formation (2, 3). In the absence of all other input, the corpora lutea subsequently fail and progesterone secretion wanes (3). It has long been appreciated that rodent corpora lutea could be maintained by either coital stimulation (4) or injection of pituitary extracts containing prolactin (PRL) activity (5, 6). An overwhelming literature now indicates that the mating stimulus induces the release of PRL which in turn “rescues” the corpora lutea of the cycle and prolongs the ability of these structures to secrete progesterone (3, 7–11). The mating stimulus or copulomimetic stimuli applied to the uterine cervix with a glass rod or appropriately...