Effect of neonatal castration on sex steroid receptor levels in the hypophysis of male rats

The content of estradiol and testosterone cytosolic and nuclear receptors has been studied in the pituitary body of adult male rats gonadectomized on day 1-3 after birth (long-term castrates) or in adulthood (short-term castrates). Intact male rats and long- and short-term castrates had the same level of cytosolic and nuclear estrogen receptors. The number of cytoplasmic and nuclear testosterone-binding sites was identical in the pituitary body of adult intact mice and long-term castrates. Contrastingly, the concentrations of androgen cytosolic and nuclear receptors were significantly lower in neonatally castrated males compared to intact adult animals. The results obtained indicate that nuclear testosterone receptors in the pituitary body mediate negative feedback effect of androgen on the release of luteinizing hormone and that the formation of thin mechanism occurs within the first days of life.     

Rapid recovery of estrogen-induced pituitary gonadotropin surges after luteectomy in rhesus monkeys

In the presence of a functional corpus luteum, positive estrogen feedback on the surge modes of gonadotropin secretion is blocked in rhesus monkeys. We investigated the effects of luteectomy (Lx) on the time required for recovery of pituitary responsiveness (LH/FSH surges) to positive estrogen feedback. Estradiol-17 beta-3- benzoate (EB, 50 microgram/kg sc) was given: 1) 24th prior to, 2) the day of, or 3) 24 h after luteal ablation. Daily measurements of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol-17 beta (e2) and progesterone (P) were made on each monkey for 5 days. Serum P fell to undetectable levels within 24 h after Lx, whereas E2 levels in circulation peaked within 24h after injection of EB. Among early follicular phase monkeys, this EB treatment results in typical midcycle type LH/FSH surges within 48h. Lx alone was not soon followed by significant changes in pituitary gonadotropin secretion. When circulating P levels were undetectable the pituitary responded fully to EB; that is, typical midcycle type FSH/LH surges occurred. When serum P was in the midst of declining after Lx, gonadotropin surges were present, but attenuated. However, when P levels remained elevated for more than 24 h after EB injection, the surge modes of FSH/LH secretion remained fully blocked. These results demonstrate that the suppressive influence of luteal secretions (principally progesterone) on positive estrogen feedback regulation of the surge modes of pituitary gonadotropin secretion is quite transient in these primates.     

A 'window of time' during which testosterone determines the opiatergic control of LH release in the adult male rat

Male rats castrated before puberty (when 26 days of age) showed a progressively decreasing susceptibility to the inhibitory effects of morphine (5 mg/kg) upon LH secretion for up to 28 days after gonadectomy (approximately 100%, 40% and 10% inhibition at 5, 12 and 28 days after castration), but thereafter morphine again caused approximately 50% reduction in serum LH values; the minimum inhibition found at 28 days after castration (age 54 days) occurred at the time at which male rats normally reach puberty. When rats were castrated at 59 days of age, morphine maximally suppressed serum LH concentrations (to less than 70%) 2 and 5 days after castration, but had no effect thereafter. In prepubertal castrates, testosterone replacement between Days 26 and 50 of life resulted in responses to morphine similar to those found in rats castrated after puberty, i.e. serum LH levels were not reduced. Morphine significantly reduced LH levels in prepubertal castrates given testosterone after 60 days of age. Treatment with morphine consistently elevated serum prolactin concentrations (greater than 100%) in castrated rats of all ages, regardless of the time elapsed after gonadectomy. These results indicate a transient fall in the inhibitory opioidergic tone upon LH secretion as the normal age of puberty approaches, that the ability of opiates to alter LH release in adulthood may depend upon testicular steroids secreted during the peripubertal period, and that the LH responses do not reflect general changes in the neuroendocrine response to opiates after castration since the prolactin response to morphine remains intact in rats castrated before and after puberty.     

The effects of castration and Silastic implants of testosterone on intermale aggression in the mouse

Castration and testosterone (T) replacement were used to study developmental changes in aggressive behavioral responsiveness to androgenic stimulation. Male mice castrated at birth were less sensitive to circulating T than were prepubertal or adult castrates, but fighting was induced in neonatal castrates with a dose of androgen that produced hypertrophy of the accessory organ system in adult castrates. Gonadectomy shortly prior to pubertal increases in serum T concentration also reduced behavioral responsiveness to androgen administration. Intermale aggression was induced in prepubertal castrates only with T treatment that maintained accessory organ growth in adult castrates. The aggressive behavior of males castrated after the pubertal surge in serum T was supported with circulating levels of androgen that failed to stimulate the accessory organ system above that of oil-treated castrates. It was concluded that T stimulation during neonatal or pubertal life is not totally crucial for organization of neural substrates that mediate the ultimate expression of intermale aggression, but exposure to androgen from birth throughout pubertal development is normally required to produce maximal aggressive behavioral responsiveness to circulating T encountered in adulthood.     

Effects of androgen administered to neonatal male rats on hypophyseal gonadotropin content, secretion and response to LHRH at adulthood

Supraphysiologic doses (1.75-3.50 mg) of testosterone propionate (TP) administered to male rats on the day of birth and 24 h later resulted in markedly reduced serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in adult males castrated for 16 days. These effects diminished as androgen was injected on succeeding postnatal days. Since exogenous dihydrotestosterone and testosterone were similarly effective, aromatization to estrogen is not required to elicit these effects. No build-up of either gonadotropin occurred in the pituitaries of TP-treated animals; pituitary LH content was appreciably reduced, while FSH remained unchanged. These data imply that hypophyseal synthesis and secretion of gonadotropins are curtailed in adult castrated males who have been androgenized neonatally. Pituitaries of such neonatally treated animals, however, were capable of increased secretion of LH in response to a challenge of luteinizing hormone-releasing hormone. These findings are compatible with a model in which an androgen suppressible event occurs at a suprahypophyseal level, e.g., hypothalamus or higher brain centers, in the male rat during a restricted neonatal period, which is responsible for programming the development of mechanisms involved in accumulation and secretion of gonadotropins.     

Effects of intermittent pulsatile infusion of luteinizing hormone-releasing hormone on dihydrotestosterone-suppressed gonadotropin secretion in castrate rams

The feedback effects of dihydrotestosterone (DHT) on gonadotropin secretion in rams were investigated using DHT-implanted castrate rams (wethers) infused with intermittent pulsatile luteinizing hormone-releasing hormone (LHRH) for 14 days. Castration, as anticipated, reduced both serum testosterone and DHT but elevated serum LH and follicle-stimulating hormone (FSH). Dihydrotestosterone implants raised serum DHT in wethers to intact ram levels and blocked the LH and FSH response to castration. The secretory profile of these individuals failed to show an endogenous LH pulse during any of the scheduled blood sampling periods, but a small LH pulse was observed following a 5-ng/kg LHRH challenge injection. Dihydrotestosterone-implanted wethers given repeated LHRH injections beginning at the time of castration increased serum FSH and yielded LH pulses that were temporally coupled to exogenous LHRH administration. While the frequency of these secretory episodes was comparable to that observed for castrates, amplitudes of the induced LH pulses were blunted relative to those observed for similarly infused, testosterone-implanted castrates. Dihydrotestosterone was also shown to inhibit LH and FSH secretion and serum testosterone concentrations in intact rams. In summary, it appears that DHT may normally participate in feedback regulation of LH and FSH secretion in rams. These data suggest androgen feedback is regulated by deceleration of the hypothalamic LHRH pulse generator and direct actions at the level of the adenohypophysis.     

Gonadotropin secretion during prolonged hyperprolactinemia: basal secretion and the stimulatory feedback effect of estrogen

Inoculation of cyclic female rats with the prolactin (Prl)/growth hormone-secreting pituitary tumor, MtT.W15, resulted in a cessation of estrous cyclicity within 5--10 days. Associated with this acyclicity was a persistently low serum concentration of estradiol and marked increases in both circulating Prl and progesterone. At Day 26 of acyclicity, basal serum luteinizing hormone (LH) values measured in samples taken every 20 min from 0900--1100 h were significantly reduced when compared to cyclic, nontumor animals on diestrus Day 2. There was no difference in basal follicle-stimulating hormone (FSH) concentrations. In a separate group of acyclic, tumor-bearing females 42--56 days after transplantation, a single s.c. injection of 20 micrograms estradiol benzoate (EB) at 1030 h elicited significant increases in both serum LH and FSH values between 1700 and 1830 h on the next day. The magnitude of the LH surge was reduced and that of FSH was increased in tumor-bearing animals when compared to cyclic, nontumor females given a similar EB injection on diestrus Day 1. These results demonstrate that chronic hyperprolactinemia is associated with inhibition of basal LH secretion and ovarian estrogen production and an increase in circulating progesterone concentrations. Nevertheless, the stimulatory feedback effects of estrogen on LH and FSH release are still present and functioning in acyclic female rats under chronically hyperprolactinemic conditions. These data suggest that the cessation of regular ovulatory cycles associated with hyperprolactinemia may be due to a deficiency of LH and/or estrogen secretion, but not to a lack of central nervous system response to the stimulatory feedback action of estrogen.     

Sexual differentiation of gonadotrophin secretion, sexual orientation and gender role behavior

The positive estrogen feedback was found to be a relatively sex-specific reaction of the hypothalamo-hypophyseal system in rats as well as in human beings. It is dependent--most of all--on the estrogen convertible androgen level during sexual brain differentiation, but also on an estrogen priming effect in adulthood. The lower the estrogen convertible androgen or primary estrogen level during brain differentiation, the higher is the evocability of a positive estrogen action on LH secretion in later life. In clinical studies, we were able to induce a positive estrogen feedback on LH secretion in most intact homosexual men in clear-cut contrast to intact hetero- or bisexual men. These findings were strongly confirmed by Gladue and associates. In addition, the evocability of a positive estrogen feedback was also demonstrable in most homosexual male-to-female transsexuals in significant contrast to hetero- or bisexual male-to-female transsexuals. These findings suggest that homosexual males possess, at least in part, a predominantly female-differentiated brain, which may be caused by a low estrogen convertible androgen level during brain organization. Recently, the following relations were found between sex hormone levels during brain differentiation and sex-specific responses in adulthood: (1) estrogens--which are mostly converted, however, from androgens--are responsible for the sex-specific organization of gonadotrophin secretion and hence the evocability of a positive estrogen feedback in later life; (2) estrogens and androgens, occurring during brain differentiation, predetermine synergistically sexual orientation and (3) androgens--without conversion to estrogens--are responsible for the sex-specific organization of gender role behaviour in later life. Furthermore, the organization periods for sex-specific gonadotrophin secretion, sexual orientation and gender role behaviour are not identical but overlapping. Thus, combinations as well as dissociations between deviations of the neuroendocrine organization of sex-specific gonadotrophin secretion, sexual orientation and gender role behaviour are conceivable. Most recently, female-type sexual orientation could be converted to male-type sexual orientation in adult rats by administration of the dopamine agonist and serotonin antagonist lisuride.     

Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator

Preovulatory GnRH and LH surges depend on activation of estrogen (E2)-inducible progesterone receptors (PGRs) in the preoptic area (POA). Surges do not occur in males, or in perinatally androgenized females. We sought to determine whether prenatal androgen exposure suppresses basal or E2-induced Pgr mRNA expression or E2-induced LH surges (or both) in adulthood, and whether any such effects may be mediated by androgen receptor activation. We also assessed whether prenatal androgens alter subsequent GnRH pulsatility. Pregnant rats received testosterone or vehicle daily on Embryonic Days 16-19. POA-hypothalamic tissues were obtained in adulthood for PgrA and PgrB (PgrA+B) mRNA analysis. Females that had prenatal exposure to testosterone (pT) displayed reduced PgrA+B mRNA levels (P < 0.01) compared with those that had prenatal exposure to vehicle (pV). Additional pregnant animals were treated with vehicle or testosterone, or with 5alpha-dihydrotestosterone (DHT). In adult ovariectomized offspring, estradiol benzoate produced a 2-fold increase (P < 0.05) in PgrA+B expression in the POA of pV females, but not in pT females or those that had prenatal exposure to DHT (pDHT). Prenatal testosterone and DHT exposure also prevented estradiol benzoate-induced LH surges observed in pV rats. Blood sampling of ovariectomized rats revealed increased LH pulse frequency in pDHT versus pV females (P < 0.05). Our findings support the hypothesis that prenatal androgen receptor activation can contribute to the permanent defeminization of the GnRH neurosecretory system, rendering it incapable of initiating GnRH surges, while accelerating basal GnRH pulse generator activity in adulthood. We propose that the effects of prenatal androgen receptor activation on GnRH neurosecretion are mediated in part via permanent impairment of E2-induced PgrA+B gene expression in the POA.     

Sexual differentiation of oestradiol-LH positive feedback in a marsupial.

The surge of LH that induces ovulation in mammals showing spontaneous ovulation is precipitated by the positive feedback of increasing oestrogens from the developing follicles in the ovary. In eutherians, exogenous oestrogens can mimic this effect by eliciting an LH surge in females, but not usually in males. The absence of a positive LH response to eutherian males is either due to an acute suppression by the secretory products of the testes during adulthood or the permanent disabling of the system by testosterone during early development. This phenomenon is examined in tammar wallabies, Macropus eugenii. The results show that the oestradiol-LH positive feedback response is sexually dimorphic in this marsupial. A surge in plasma LH occurred between 15 and 28 h after injection of 2.5 micrograms oestradiol benzoate kg-1 in 13 of 16 intact females and 4 of 4 ovariectomized females, but in none of 11 intact males. Five females each implanted with a 100 mg testosterone pellet 3 months earlier failed to produce an LH surge. Four males castrated in adulthood and three adult males castrated before puberty also failed to show an LH surge. However, three males castrated 24-26 days after birth showed an unambiguous LH surge when challenged with oestradiol benzoate during adulthood. Thus, in tammar wallabies, the ability to generate an LH surge to oestradiol is a sexually dimorphic response that is suppressed in the male by the organizational effects of the testes in early life and presumably supplemented by an inhibitory effect of circulating testosterone in adulthood.     

Sexual differentiation of the steroid feedback mechanism regulating follicle-stimulating hormone secretion in the Syrian hamster

The ability of gonadal steroid hormones to influence tonic follicle-stimulating hormone (FSH) secretion was investigated in Syrian hamsters. In Experiment 1, males were castrated as adults, and administered testosterone in 20-, 30-, 40-, and 50-mm silastic capsules (s.c.) at 67, 74, 81, and 88 days, respectively. Circulating FSH was reduced by testosterone in a dose-dependent manner. A similar FSH response to testosterone in adulthood was evident in neonatally androgenized hamsters given testosterone proprionate (TP) on Days 0 and 1 of life. By contrast, the absence of gonadal androgens during the neonatal period (females ovariectomized at 60 days of age and males orchidectomized at birth) resulted in only a partial suppression of circulating FSH by even the highest dose of testosterone during adulthood. Treatment with estradiol benzoate at birth failed to produce a masculine response to androgen in adulthood. In Experiment 2, using a similar protocol, the nonaromatizable androgen, dihydrotestosterone, produced a dose-dependent suppression in serum FSH in males castrated in adulthood (30-, 60-, 90-mm capsules). However, dihydrotestosterone failed to alter the hypersecretion of FSH produced by orchidectomy at birth in males or in females ovariectomized at 60 days of age and treated neonatally with either vehicle or TP. In Experiment 3, treatment with estradiol (10-, 20-, 30-mm capsules) decreased serum FSH in gonadectomized hamsters in a dose-dependent manner; males and females treated neonatally with TP were more responsive to estradiol as adults compared to neonatally orchidectomized males or females treated with vehicle at birth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys

Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.     

Modifications of the gonadal function in the adult rat after fetal exposure to spironolactone

The effects of fetal exposure to spironolactone (SPL), an aldosterone antagonist with weak antiandrogen and gestagen properties, upon the pituitary-gonadal axis were studied in the offspring of rats that had been treated daily from gestation day 14 to day 20 with 10 or 20 mg SPL or the solvent vehicle (for controls). At 70-80 days of age, SPL-exposed rats showed no alterations in external genitalia or in body weight. However, males displayed a dose-dependent decrease in the weights of the ventral prostate and seminal vesicles. Whereas basal and gonadotropin-releasing hormone (GnRH)-induced plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and 5 alpha-dihydrotestosterone levels were similar to controls, basal plasma and pituitary prolactin (Prl) levels were reduced (SPL-exposed 6.8 +/- 1.0 vs. controls 15.8 +/- 2.8 ng/ml and 6.1 +/- 1.2 vs. 11.6 +/- 1.8 microgram/anterior pituitary gland; mean +/- SEM). Cytosolic androgen receptors in ventral prostate were nonsignificantly decreased, but they increased after GnRH in contrast to controls. Nuclear androgen receptors were normal. Females displayed normal estrous cycles. Basal and GnRH-induced plasma FSH, Prl, estradiol, and progesterone concentrations were similar to controls, whereas plasma LH was elevated. Estrogen receptors in uterine cytosol were low and increased after GnRH. Ovaries and uteri were enlarged. The present study demonstrates that in utero exposure to SPL leads to endocrine dysfunctions that persist into adulthood. They are characterized in males by hypoprolactinemia, reduced weights of accessory sex organs, and a suggestion of functional modifications of androgen receptors. In females they are characterized by increased LH secretion, increased ovarian and uterine weights, and decreased uterine cytosol estrogen receptors, suggesting enhanced estrogenic action.     

Proliferative response of seminal vesicle cells to androgen in mice castrated neonatally and pretreated with estrogen or androgen at adulthood

Seminal vesicle cells of neonatally castrated adult mice show poor response to androgen, compared to those of mice castrated at adulthood; effects of pretreatment with androgen or estrogen at adulthood on androgen-induced proliferation of the seminal vesicle cells were examined in neonatally castrated mice. Male mice castrated at day 0 after birth were pretreated with daily injections of testosterone propionate (TP, 100 micrograms/mouse), 17 beta-estradiol (E2, 5 micrograms/mouse) or vehicle for 20 days starting from day 60; daily TP injections (100 micrograms/mouse) for 30 days were started again from day 110 in all the pretreated mice to examine androgen-induced proliferation by incorporation of 5-[125I]iodo-2'-deoxyuridine into the whole seminal vesicles. Both TP and E2 pretreatments significantly increased the seminal vesicle weight found before TP treatment. However, androgen-induced proliferation of the seminal vesicle found in neonatally castrated mice (poor response; long duration with a low peak on day 3) was changed at least in part to that found in mice castrated at adulthood (good response; short duration with a high peak on day 3) only following the TP pretreatment but not at all following the E2 pretreatment. The E2 pretreatment induced poor androgen-induced proliferation with a low peak on day 7.     

Gonadal steroid modulation of brain opioid systems

It is becoming increasingly clear that the effects of the opioids and their synthetic analogs on anterior pituitary function largely depend on the steroid milieu present in the animal at time of drug administration. However, it is still unclear whether gonadal steroids regulate the opioid-modulated mechanisms by affecting the number of opiate receptors in the brain. To further investigate these issues, the effects of opiate agonists and antagonists on LH, FSH and prolactin (Prl) secretion have been studied in: (a) normal and castrated male rats, and (b) normally cycling female rats. The binding characteristics of the brain subclass of mu opiate receptors have been analyzed in the same group of experimental animals; this type of receptors seems to be particularly involved in the control of gonadotropin and Prl release. When injected intraventricularly into normal male rats, morphine (200 micrograms/rat) induced in a significant elevation of serum LH levels at 10 and 20 min. In long-term castrated animals the administration of the drug significantly reduced LH secretion at 40 and 60 min after the injection, the inhibition lasted up to 180 min. Morphine, when given intraventricularly to normal males, induced a conspicuous and significant elevation of serum Prl levels at 10, 20, 40 and 60 min after treatment. However, when the drug was administered to castrated rats, it did not significantly affect Prl release at any time interval considered. Morphine intraventricular injections did not modify serum FSH levels either in normal or in castrated male rats. The concentration of mu opiate receptors was found to be similar when measured in the whole brain of normal and orchidectomized rats. In adult cycling female rats, s.c. injections of naloxone (2.5 mg/kg) stimulated LH release in every phase of the estrous cycle; the magnitude of the responses was highly variable, being particularly elevated at 16.00 h of the day of proestrous and at 10.00, 12.00 and 14.00 h of the day of estrous. Conversely, LH response to naloxone was totally obliterated at 18.00 and 20.00 h of the day of proestrous, when the preovulatory LH surge was found to occur. The concentration of brain opiate receptors of the mu type showed significant variations during the different phases of the estrous cycle, with higher levels at 12.00 h of the day of proestrous and at 18.00 h of the day of estrous.(ABSTRACT TRUNCATED AT 400 WORDS)     

Testicular involvement in peripubertal gonadotropin levels and accessory sex organ weight of male hamsters

This study evaluates the influence of testicular secretions during development in male hamsters on peripubertal gonadotropin levels. Castration or sham operations were performed on the day of birth (Day 1), Day 5, 10, or 20 of life. Repeated plasma samples on Days 20-60 at 10-day intervals were taken via orbital sinus puncture. Castrated animals received a subcutaneous testosterone capsule on Day 60 and were killed on Day 70. In addition, seminal vesicles and ventral prostate weights were taken in all animals at Day 70. Castrated animals, regardless of day of castration, had higher gonadotropin levels and suppressed sexual accessory organ weights. Animals castrated on the day of birth had lower luteinizing hormone (LH) levels than animals castrated on other days. Castration on Day 10 resulted in lower follicle stimulating hormone (FSH) levels. Males castrated on Day 20 were most sensitive to the negative feedback effect of testosterone on LH secretion, while Day 10 castrates had elevated FSH levels after testosterone exposure. Sexual accessory weights also differed depending upon the day of castration. Results point out the importance of testicular secretions on the developmental processes as well as the differing ages at which various systems may be influenced.     

Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys

Experimentally induced fetal androgen excess induces polycystic ovary syndrome-like traits in adult female rhesus monkeys (Macaca mulatta). Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily s.c. injections of 15 mg of testosterone propionate (TP), and six received injections of oil vehicle (control) from 40 through 80 days of gestation (term, 165 days; range, +/-10 days). All fetuses were delivered by cesarean section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. The TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels returned to values within the reference range for animals in these age groups, whereas serum androstenedione levels in PA infants were elevated. The TP injections did not increase estrogen levels in the dams or the PA fetuses or infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late-gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood.     

Effect of time after castration on secretion of LHRH and LH in the ram

Hypophysial portal blood and peripheral blood were obtained from conscious, unrestrained rams to measure simultaneously the secretion of LHRH and LH in entire rams and rams which had been castrated for 2-15 days (short-term castration) and for 1-6 months (long-term castration). The apparatus for portal blood collection was surgically implanted using a transnasal trans-sphenoidal approach and, 4-5 days later, portal blood and peripheral blood were collected simultaneously at 10-min intervals for 8-9 h from 15 sheep. LHRH was clearly secreted in pulses in all three physiological conditions, but there were marked differences in pulse frequencies, which averaged 1 pulse/2-4 h in entire rams, 1 pulse/70 min in short-term castrated rams and 1 pulse/36 min in long-term castrated rams. In entire and short-term castrated animals, LH profiles were also clearly pulsatile and each LHRH pulse in hypophysial portal blood was associated with an LH pulse in the peripheral blood. In long-term castrated animals, LH pulses were not as well defined, because of the high basal levels and small pulse amplitudes, and the temporal relationship between LHRH and LH pulses was not always clear. These results demonstrate the pulsatile nature of LHRH secretion under the three physiological conditions and suggest that the irregular LH profiles characteristic of long-term castrates are due to an inability of the pituitary gland to transduce accurately the hypothalamic signal. The very high frequency of the LHRH pulses may be one of the major reasons for this, and is probably also responsible for the high rate of LH secretion in the long-term castrated animal.     

Central effects of an antagonist and an antiserum to substance P on serum gonadotropin and prolactin secretion

The central effects of both an antagonist and an antiserum to substance P (SP) on gonadotropin and prolactin (Prl) secretion were studied in castrated male rats. The lateral ventricular injection (20 micrograms) of an analogue to SP possessing antagonistic properties resulted in significantly suppressed serum LH levels without altering serum FSH and Prl levels when compared with saline-injected control animals. Similarly, the lateral ventricular injection of an antiserum to SP also resulted in significantly suppressed LH levels when compared to control animals injected with normal rabbit serum. Additionally, no changes were observed in the levels of serum FSH and Prl as a result of the anti-SP injection. Thus, although indirect, these results support the hypothesis that SP may have a central stimulatory action on LH secretion, but not FSH and Prl secretion.     

A functional dimorphism in the response of the hypothalamic-pituitary axis of prepubertal rats to steroid treatment

In the present experiment we examined the circadian neural luteinizing hormone releasing hormone (LHRH) and serum luteinizing hormone (LH) response of prepubertal male and female rats under varying steroidal manipulations (Intact, Castrate, Castrate + estradiol 17 beta [E2] + oil and Castrate + E2 + progesterone[P]). Prepubertal males demonstrated greater and acyclic LHRH concentrations in both the medial basal hypothalamus (MBH) and preoptic-suprachiasmatic regions (POA-Sch) irrespective of steroid treatment. In steroid-treatment castrated male rats only the negative feedback action on serum LH levels were observed with maximal effect in animals injected with the combination E2 + P. In contrasts, prepuberal castrated females exhibited both inhibitory and stimulatory feedback actions on LH release following steroid treatment. Moreover, a distinctive, significant, progesterone-dependent increase in AM POA-Sch, but not MBH-LHRH concentrations was detected. These results demonstrate the existence of a functional sexual dimorphism in the positive feedback response of the POA-Sch-pituitary axis of prepubertal rats to progesterone treatment.