Regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) gene expression by gonadotropin-releasing hormone (GnRH) and sexual steroids in the Mediterranean Sea bass

The secretion of gonadotropins, the key reproductive hormones in vertebrates, is controlled from the brain by the gonadotropin-releasing hormone (GnRH), but also by complex steroid feedback mechanisms. In this study, after the recent cloning of the three gonadotropin subunits of sea bass (Dicentrarchus labrax), we aimed at investigating the effects of GnRH and sexual steroids on pituitary gonadotropin mRNA levels, in this valuable aquaculture fish species. Implantation of sea bass, in the period of sexual resting, for 12 days with estradiol (E2), testosterone (T) or the non-aromatizable androgen dihydrotestosterone (DHT), almost suppressed basal expression of FSHbeta (four to 15-fold inhibition from control levels), while slightly increasing that of alpha (1.5-fold) and LHbeta (approx. twofold) subunits. Further injection with a GnRH analogue (15 microg/kg BW; [D-Ala6, Pro9-Net]-mGnRH), had no effect on FSHbeta mRNA levels, but stimulated (twofold) pituitary alpha and LHbeta mRNA levels in sham- and T-implanted fish, and slightly in E2- and DHT-implanted fish (approx. 1.5-fold). The GnRHa injection, as expected, elevated plasma LH levels with a parallel decrease on LH pituitary content, with no differences between implanted fish. In conclusion, high circulating steroid levels seems to exert different action on gonadotropin secretion, inhibiting FSH while stimulating LH synthesis. In these experimental conditions, the GnRHa stimulate LH synthesis and release, but have no effect on FSH synthesis.     

Effect of vitamin A deficiency upon gonadotropin response to gonadotropin-releasing hormone

There is a monotypic change in basal serum gonadotropin levels following retinol treatment of chronically vitamin A-deficient (VAD) male rats. The present study was undertaken to investigate the hypothesis that the specific increase in serum follicle-stimulating hormone (FSH) represents a change in gonadotrope responsiveness to gonadotropin-releasing hormone (GnRH). To this end, a test dose of GnRH was given to VAD rats pre-, 5 days post-, and 10 days postreplacement of vitamin A (PVA). In VAD rats, basal serum FSH and luteinizing hormone (LH) levels were higher than those of controls. Increased LH/testosterone ratios, both in basal levels and in the secretory response to GnRH, suggested Leydig cell hyporesponsiveness in VAD animals. Both the FSH and LH responses to GnRH were maximal at 1 h, declining thereafter. Although the absolute increments in FSH and LH 1 h after GnRH in VAD rats were greater than in controls, the percent increase in FSH tended to be lower in VAD rats and to increase after vitamin A replacement. The specific enhancement of FSH release PVA became evident only when assessing total secretion of FSH and LH after GnRH. Luteinizing hormone response to GnRH increased PVA, but not significantly, while FSH secretion after GnRH increased both 5 and 10 days PVA, times during which basal FSH levels were also increasing. These changes in FSH secretion could not be attributed either to increases in endogenous GnRH or to changes in testosterone or estradiol levels. Basal serum androgen binding protein levels, elevated in VAD animals, did not respond to the acute increases in FSH after GnRH and remained high PVA, suggesting no acute change in Sertoli cell function. Thus, the PVA increase in FSH secretion unmasks a partial inhibition of the gonadotrope present in the retinol-deficient, retinoic acid-fed male rat.     

Lithium-induced changes in the plasma and pituitary levels of luteinizing hormone,follicle stimulating hormone and prolactin in rats

Adult male Sprague-Dawley rats, maintained under a controlled photoperiod of LD 14:10 (white lights on at 06:00 h, CST), were injected with lithium chloride and changes in the levels of plasma and pituitary homogenates of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were examined to evaluate the effects of this anti-manic drug on reproductive function. Two groups of rats were injected with lithium chloride intraperitoneally, twice daily at 09:00 and 16:00 h, for 2 and 7 days at a dosage of 2.5 meg/Kg body weight. Plasma and pituitary levels of LH, FSH and PRL were measured by radioimmunoassay. Plasma levels of LH were significantly (P<0.05) increased after 2 days of lithium treatment. In contrast, a significant (P<0.005) reduction in plasma levels of LH was evident when lithium injections were continued for 7 days. The plasma levels of FSH remained unaffected by lithium treatment by either time period. Lithium administered for 2 days did not bring about any significant alteration in the plasma levels of PRL, although there was a significant (P<0.002) reduction in plasma PRL levels after 7 days treatment. The concentrations of pituitary LH, FSH and PRL remained unchanged after 2 and 7 days of lithium treatment.     

Effects of luteinizing hormone releasing hormone on gonadotrophins in the hamster

The changes in serum gonadotrophins in male hamsters following one injection of 15 μg luteinizing hormone releasing hormone (LHRH) (Group A) were compared with those following the last injection of LHRH in animals receiving an injection approximately every 12 hr for 4 days (Group B) or 12 days (Group C). Peak follicle stimulating hormone (FSH) levels (ng/ml) were 1776±218 (Group A), 2904±346 (Group B), and 4336±449 (Group C). Peak luteinizing hormone (LH) values (ng/ml) were 1352±80 (Group A), 410±12 (Group B), and 498±53 (Group C). Serum FSH:LH ratios, calculated from the concentrations measured 16 hr after the last LHRH injections, were higher in Groups B and C than in Group A. Similar injections of LHRH (100 ng or 15 μg/injection) for 6 days elevated the serum FSH:LH ratio in intact males. Five such LHRH injections (100 ng/injection) blunted the rise in serum LH in orchidectomized hamsters. Direct effects of LHRH on gonadotrophin secretory dynamics or altered brain-pituitary-testicular interactions may alter the ratio of FSH to LH in the hamster.     

Age-dependent effect of Freund's adjuvant on 24-hour rhythms in plasma prolactin, growth hormone, thyrotropin, insulin, follicle-stimulating hormone, luteinizing hormone and testosterone in rats

The effect of Freund's adjuvant administration on 24-hour changes of plasma prolactin, growth hormone (GH), thyrotropin (TSH), insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were studied in young (2 months) and aged (18 months) male Wistar rats. Rats were injected s.c. with Freund's adjuvant or adjuvant's vehicle and, 18 days later, they were killed at 6 different time intervals throughout a 24-hour cycle to measure circulating hormone levels by specific RIAs. Young rats receiving adjuvant's vehicle exhibited significant time-of-day-dependent variations in plasma TSH, LH and testosterone, with maximal levels at 1300 h, 0100 h and 1700 h, respectively. Prolactin and insulin levels, analyzed globally in a factorial ANOVA, showed significant time-of-day changes with maximal levels at 1300 - 1700 h and 2100 h, respectively. The daily rhythms in plasma LH and testosterone found in young rats were not longer observed in Freund's adjuvant-injected rats, while as far as TSH, a second peak was observed at 0100 h after Freund's adjuvant administration. Twenty-four hour rhythms in circulating TSH, LH and testosterone were blunted in old rats receiving either Freund's adjuvant or its vehicle. Aged rats exhibited significantly higher circulating levels of prolactin, and lower levels of GH, TSH, FSH and testosterone. The results indicate that secretion of prolactin, GH, TSH, FSH and testosterone are age-dependent, as are the responses of TSH, LH and testosterone to Freund's adjuvant administration.     

Effects of a potent antagonist to gonadotropin-releasing hormone on male rats: luteinizing hormone is suppressed more than follicle-stimulating hormone

Previous work with female rats showed that serum levels of follicle-stimulating hormone (FSH) are suppressed by gonadotropin-releasing hormone (GnRH) antagonists less than are levels of serum luteinizing hormone (LH), suggesting a lesser dependency of FSH on GnRH stimulation. The differential regulation of LH and FSH is known to have some aspects that are sexually asymmetrical, and it was of interest to see if males also show differential gonadotropin suppressibility after injection of an antagonist to GnRH. Male rats were prepared for serial sampling 4 wk after castration. After a blood sample was removed at Time Zero, [Ac-3-Pro1, pF-D-Phe2, -D-Trp3,6]-GnRH (Antag) was injected subcutaneously in oil; doses were 0, 4, 20, 100, 500, and 2500 micrograms. Blood was sampled at 2, 5, 12, 24 and 36 h postinjection. All doses above 4 micrograms had lowered LH levels by 2 h, and LH remained suppressed for 12 to 24 h at the three higher doses. By contrast, serum FSH was unaffected by any dose at 5 h, and was only marginally suppressed by the highest doses thereafter. As in females, therefore, FSH secretion in male rats appears not to be as dependent on GnRH as is LH secretion.     

Possible involvement of inhibin in altered follicle-stimulating hormone (FSH) secretion during dissociated luteinizing hormone (LH) and FSH release: unilateral castration and experimental cryptorchidism

Male rats were either unilaterally or bilaterally castrated, or were rendered cryptorchid when they were either 15 or 45 days old. Subsequently, blood was sampled over the next several weeks and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and immunoreactive inhibin-alpha (irI alpha) levels were measured by specific radioimmunoassays (RIAs). At the end of the experiment, gonadal expression of inhibin-alpha, inhibin-beta A, and inhibin-beta B subunits was measured by S1 nuclease analysis and in situ hybridization. In both age groups, bilateral castration (BC) produced the expected marked (p less than or equal to 0.01) increases in plasma LH and FSH levels, and concomitant decreases in T and irI alpha secretion within 1 - 2 days after surgery. In 15-day-old animals, unilateral castration (UC) significantly increased FSH and decreased circulating levels of irI alpha, but did not measurably alter LH or androgen production. At 7 days after surgery, the level of inhibin mRNA in the remaining testis was unchanged. In 45-day-old animals, UC caused a measurable increase in FSH, with little or no changes in the circulating levels of irI alpha. Plasma T levels were lowered (p less than or equal to 0.05) by UC; however, there were no statistical changes in LH levels in these UC rats. Finally, T administration markedly reversed UC-induced increase in FSH secretion in both age groups. Androgen therapy also interfered with inhibin release in 45-day-old, but not in 15-day-old rats. In rats 15 days old at the time of surgery, cryptorchidism produced a small but measurable increase (p less than or equal to 0.05) in LH release at Week 6 only, which was accompanied by a significant (p less than or equal to 0.01) decline in T secretion. Plasma FSH levels were elevated at all times in cryptorchid rats, and at 2, 4, and 6 wk, these levels were not statistically distinguishable (p greater than 0.05) from those of castrated animals. In this group of rats, cryptorchidism caused a transient increase (p less than or equal to 0.05) in irI alpha values 1 wk after surgery, but no changes at later times. Finally, measurement of testicular inhibin-alpha subunit messenger RNA (mRNA) levels showed an approximately 2-fold increase compared to total RNA levels in the testis. However, because of the significant decrease in total RNA levels per testis caused by cryptorchidism, the absolute change in inhibin-alpha subunit mRNA levels per testis corresponded to an approximately 3-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective release of follicle-stimulating hormone by 5 alpha-dihydroprogesterone in immature ovariectomized estrogen-primed rats

The effect of 5 alpha-dihydroprogesterone (5 alpha-DHP) on gonadotropin release was examined in the immature acutely ovariectomized (OVX) rat primed with a low dose of estradiol (E2). Treatment with various doses of 5 alpha-DHP given in combination with E2 increased levels of follicle-stimulating hormone (FSH) but had no effect on serum luteinizing hormone (LH). A single injection of a maximally stimulating dose of 5 alpha-DHP (0.4 mg/kg) stimulated increases in serum FSH at 1200 h and, 6 h later, at 1800 h. Pituitary LH and FSH content was dramatically enhanced by 1600 h and levels remained elevated at 1800 h. The administration of pentobarbital at 1200 h, versus 1400 h or 1600 h, prevented the increase in basal serum FSH levels at 1800 h, implying that the release of hypothalamic LH releasing hormone (LHRH) is modulated by 5 alpha-DHP. In addition, changes in pituitary sensitivity to LHRH as a result of 5 alpha-DHP were measured and a significant increase in the magnitude of FSH release was observed at 1200 h and 1800 h. Although the LH response to LHRH in 5 alpha-DHP-treated rats was not different from controls, the duration of LH release was lengthened. These results suggest that 5 alpha-DHP may stimulate FSH release by a direct action at the pituitary level. Together, these observations support the theory that 5 alpha-DHP mediates the facilitative effect of progesterone on FSH secretion and further suggests an action of 5 alpha-DHP in this phenomenon at both pituitary and hypothalamic sites.     

Selective release of luteinizing hormone by 3 alpha-hydroxy-5 alpha-pregnan-20-one in immature ovariectomized estrogen-primed rats

This study investigated the role of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP) in the modulation of gonadotropin secretion using the immature ovariectomized (OVX) rat primed with a low dose of estradiol. A treatment regimen of either 0.2 or 0.4 mg/kg of 3 alpha,5 alpha-THP given in conjunction with estradiol for 4 days significantly increased levels of serum luteinizing hormone (LH) but had no effect on serum follicle-stimulating hormone (FSH). Estrogen-primed rats receiving a single injection of 3 alpha,5 alpha-THP at 0930 h showed an increase in serum and pituitary LH levels at 1200 h and 1500 h. At 1800 h, only pituitary levels of LH remained significantly higher than controls. An injection of 3 alpha,5 alpha-THP at 1230 h in estrogen-primed rats resulted in enhanced levels of pituitary LH at 1500 h and elevated levels of both serum and pituitary LH at 1800 h. When 3 alpha,5 alpha-THP was given at 0930 h and 1230 h, elevated serum levels of LH were maintained for over 6 h. The administration of pentobarbital (Pb) 30 min after an injection of 3 alpha,5 alpha-THP at 0930 h or 1230 h prevented the increases in serum LH at 1200 h, 1500 h or 1800 h. This suggests that LH-releasing hormone (LHRH) is involved in mediating the LH response by 3 alpha,5 alpha-THP. There was no change in the sensitivity of the pituitary to LHRH following 3 alpha,5 alpha-THP treatment, indicating the absence of a pituitary effect of this steroid.     

The effects of porcine follicular fluid inhibin on gonadotropin secretion in the rabbit

Porcine follicular fluid (pff), treated with charcoal to remove steroids, was used to determine whether inhibin is active in the laboratory rabbit. When pff (5 ml/4 kg body weight) was injected (ip) into does that had been castrated 2 weeks earlier, there was a significant decline in blood follicle-stimulating hormone (FSH) levels; the decline lasted for 8-12 h. Blood levels of luteinizing hormone (LH) were suppressed, but only briefly at 3 h after injection. In other experiments, intact does which had been injected with pff 9 h and 10 min before receiving a single, i.v. injection of luteinizing hormone-releasing hormone (LHRH) (10 micrograms/kg body weight) showed a sharp reduction in the concentration of LH in the blood samples collected 15, 30 and 60 min after LHRH administration. Secretion of FSH responded poorly to LHRH stimulation, and pff had little suppressive action on blood levels. Having established that the pff preparation had inhibin activity, its action on the postovulatory surge of FSH secretion was next examined. This release of FSH, which occurs 6 to 36 h after ovulation, has been hypothesized to be required for the establishment of pregnancy by stimulating the growth of the ovarian follicles supplying the luteotropic estradiol. To test this hypothesis, pff was injected into rabbits every 8 h for the first 5 days of pregnancy and found to block the postovulatory FSH surge. The patterns of secretion of LH and progesterone in the same pff-injected animals were, however, not altered from normal pregnancy patterns by pff.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of exogenous testosterone on testicular luteinizing hormone and follicle-stimulating hormone receptors during aging

During aging, the male Japanese quail exhibits a loss of fertility, increased morphological abnormalities in the testes, and a higher incidence of Sertoli cell tumors. Although there is a coincident loss of reproductive behavior, plasma androgen levels remain high until testicular regression occurs in association with senescence. The purpose of this study was to compare mean specific binding of chicken luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as a measure of testicular receptors during identified stages during aging. Males were categorized according to age (young = 9 months, middle aged = 24 months, or old = 36+ months) and sexual behavior (active or inactive). Testicular samples were collected immediately after perfusion with 4% paraformaldehyde from the following groups: young active (n = 8), young photoregressed (n = 5), young photoregressed plus testosterone implant (n = 4), middle-aged active (n = 8), middle-aged inactive (n = 4), old inactive (n = 5), and old inactive plus testosterone implant (n = 6). A crude plasma membrane fraction was prepared from the testes of each bird and an aliquot deriving from 10 mg of testicular tissue was used for binding assay. Specific binding of labeled LH or FSH was expressed as percentage of total radioactive hormone. Results showed significant (P < 0.05) age-related decreases in both FSH and LH receptor numbers. The highest FSH binding was found in young and middle-aged active males, with low binding in old inactive males. Testicular LH binding decreased during aging, with a sharp decrease in middle-aged males, which was similar to old males. Testosterone implants weakly stimulated FSH and LH binding in old males. Both LH and FSH binding decreased in photoregressed young males. However, testosterone implants stimulated increased LH binding, but did not affect FSH binding in young photoregressed males. These results provide evidence for separate regulation of testicular LH and FSH receptors, with testosterone stimulation of LH receptor, but not FSH receptor number in young males. However, during aging there appears to be a loss of this response, potentially because of the reduced efficacy of testosterone stimulation, thereby implying a diminished capacity for response with aging.     

Short-term pulsatile administration of luteinizing hormone releasing hormone in male adolescents with multiple idiopathic pituitary hormone deficiencies

In order to define both level and severity of defect in patients with idiopathic multiple pituitary hormone deficiencies (MPHD) and to find out which patient might benefit from pulsatile LHRH substitution therapy, the effect of short-term pulsatile LHRH infusion in 6 affected male adolescents was studied. Controls were 9 boys with constitutional delay of puberty (CD). During a spontaneous nocturnal plasma profile LH and FSH levels were prepubertal with little evidence of pulsatile secretory LH activity in all MPHD patients. During short-term pulsatile LHRH stimulation (36 h), however, all showed a significant rise in mean LH and FSH levels (p less than 0.0001). Linear regression analysis revealed significant continuous increases of FSH (p less than 0.001) in all patients and of LH (p less than 0.01) in all but one patient. These changes were not accompanied by an increase of testosterone, androstenedione and DHAS levels. Since all MPHD patients showed steadily increasing gonadotropin levels if stimulated in a pulsatile manner, we conclude that the defect might only in part be located at the pituitary level. Long-term pulsatile substitution therapy with LHRH is likely to be successful in these patients as has been demonstrated in patients with known hypothalamic defect.     

Early pituitary follicle stimulating hormone response to gonadotrophin releasing hormone in ewes

The object of our experiments was to characterize the response of plasma follicle stimulating hormone (FSH) within minutes of an i.v. injection of high or low doses of gonadotrophin releasing hormone (GnRH), especially in relation to contemporary changes in luteinizing hormone (LH) concentrations. In the deep anoestrous period (June), three intact ewes and two ovariectomized ewes were injected with 1 mug synthetic GnRH followed 2 h later by a second identical injection. A week later, the same regimen was repeated with the same sheep but with 50 mug GnRH after an interval of 5 h 20 min. Blood samples were collected every 15 sec for 15 min after each injection (early release), then at longer intervals (main release) till the next treatment, followed by sampling for a further 6-h period after the second treatment. FSH was released as soon as the second minute after GnRH injection in all ewes. The mean pituitary FSH response, during this early release, in intact and ovariectomized ewes was similar after either 1 or 50 mug GnRH. However, the main release was less pronounced in the ovariectomized sheep and was not stimulated after the second treatment in all sheep. Three other ewes were injected with 40 mug GnRH and sampled every 15 sec for seven, 6-min periods during the period of release to compare FSH and LH secretion. The profiles reflected a similarity in sensitivity and responsiveness to GnRH, especially soon after GnRH injection. Increases in both hormones were formed by several grouped associated spikes. It is suggested that a readily releasable pool of FSH exists in the ewe. There are probably differences in the mechanisms of synthesis and/or release between pituitary FSH and LH.     

Effect of gonadotropin-releasing hormone antagonists on serum follicle-stimulating hormone and luteinizing hormone under conditions of singular follicle-stimulating hormone secretion

Previous work has indicated that in long-term ovariectomized rats a potent antagonist to gonadotropin-releasing hormone (GnRH) suppressed serum luteinizing hormone (LH) more successfully than follicle-stimulating hormone (FSH). The present studies examined whether the rise in serum FSH which occurs acutely after ovariectomy, or during the proestrous secondary surge, depends on GnRH. In Experiment A, rats were ovariectomized at 0800 h of metestrus and injected with (Ac-dehydro-Pro1, pCl-D-Phe2, D-Trp3,6, NaMeLeu7)-GnRH (Antag-I) at 1200 h of the same day, or 2 or 5 days later. Antag-I blocked the LH response completely, but only partially suppressed serum FSH levels. Experiment B tested a higher dose of a more potent antagonist [( Ac-3-Pro1, pF-D-Phe2, D-Trp3,6]-GnRH; Antag-II) injected at the time of ovariectomy. The analog suppressed serum LH by 79% and FSH by 30%. Experiment C examined the effect of Antag-II on the day of proestrus on the spontaneous secondary surge of FSH, as well as on a secondary FSH surge which can be induced by exogenous LH. Antag-II, given at 1200 h proestrus, blocked ovulation and the LH surge expected at 1830 h, as well as increases in serum FSH which occur at 1830 h and at 0400 h. Exogenous LH triggered a rise in FSH in rats suppressed by Antag-II. In Experiment D proestrous rats were injected with Antag-II at 1200 h and ovariectomized at 1530 h. By 0400 h the antag had suppressed FSH in controls, but in the ovariectomized rats, a vigorous FSH response occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effect of cyanoketone on follicle-stimulating hormone (FSH) induction of receptors for FSH in granulosa cells of the rat

Follicle-stimulating hormone (FSH) enhances the conversion of testosterone or androstenedione into estradiol by stimulating the aromatase enzyme system. Estradiol also enhances FSH action. Thus, a synergistic action of FSH and estradiol may be required for maturation of ovarian follicles. We hypothesized that estradiol may be required for FSH action. Thus, blocking estrogen synthesis should prevent FSH-induced increases in FSH receptors. Hypophysectomized rats were divided into five groups and injected subcutaneously with: 1) saline, 2) cyanoketone (0.05 mg, blocks the conversion of pregnenolone to progesterone), 3) ovine FSH (oFSH, 200 micrograms), 4) cyanoketone then oFSH 24 h later, or 5) cyanoketone plus estradiol [or progesterone, testosterone, promegestrone (R5020), dihydrotestosterone (DHT), 2 mg], then FSH 24 h later. Animals were decapitated at 0, 12 or 24 h after an injection of oFSH, and membrane receptors for FSH and luteinizing hormone (LH), plus nuclear receptors for estradiol from granulosa cells, were measured. LH receptor levels were increased only after administration of FSH and estradiol. At 0 and 24 h, numbers of FSH or estradiol receptors were similar in saline- and cyanoketone-treated animals. FSH alone increased (P less than 0.01) FSH and estradiol receptors 3-fold and 4-fold, respectively, over controls by 12 and 24 h. Cyanoketone prevented these increases in FSH and estradiol receptors. Estradiol replacement fully reversed the effects of cyanoketone on FSH action. Replacement with progesterone and testosterone was able to only partially restore levels of FSH receptors; however, estradiol receptor numbers were also increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hyperprolactinemia on the control of luteinizing hormone and follicle-stimulating hormone secretion in the male rat

Experiments were conducted to determine the effects of acute hyperprolactinemia (hyperPRL) on the control of luteinizing hormone and follicle-stimulating hormone secretion in male rats. Exposure to elevated levels of prolactin from the time of castration (1 mg ovine prolactin 2 X daily) greatly attenuated the post-castration rise in LH observed 3 days after castration. By 7 days after castration, LH concentrations in the prolactin-treated animals approached the levels observed in control animals. HyperPRL had no effect on the postcastration rise in FSH. Pituitary responsiveness to gonadotropin hormone-releasing hormone (GnRH), as assessed by LH responses to an i.v. bolus of 25 ng GnRH, was only minimally effected by hperPRL at 3 and 7 days postcastration. LH responses were similar at all time points after GnRH in control and prolactin-treated animals, except for the peak LH responses, which were significantly smaller in the prolactin-treated animals. The effects of hyperPRL were examined further by exposing hemipituitaries in vitro from male rats to 6-min pulses of GnRH (5 ng/ml) every 30 min for 4 h. HyperPRL had no effect on basal LH release in vitro, on GnRH-stimulated LH release, or on pituitary LH concentrations in hemipituitaries from animals that were intact, 3 days postcastration, or 7 days postcastration. However, net GnRH-stimulated release of FSH was significantly higher by pituitaries from hyperprolactinemic, castrated males. To assess indirectly the effects of hyperPRL on GnRH release, males were subjected to electrical stimulation of the arcuate nucleus/median eminence (ARC/ME) 3 days postcastration. The presence of elevated levels of prolactin not only suppressed basal LH secretion but reduced the LH responses to electrical stimulation by 50% when compared to the LH responses in control castrated males. These results suggest that acute hyperPRL suppresses LH secretion but not FSH secretion. Although pituitary responsiveness is somewhat attenuated in hyperprolactinemic males, as assessed in vivo, it is normal when pituitaries are exposed to adequate amounts of GnRH in vitro. Thus, the effects of hyperPRL on pituitary responsiveness appear to be minimal, especially if the pituitary is exposed to an adequate GnRH stimulus. The suppression of basal LH secretion in vivo most likely reflects inadequate endogenous GnRH secretion. The greatly reduced LH responses after electrical stimulation in hyperprolactinemic males exposed to prolactin suggest further that hyperPRL suppresses GnRH secretion.     

The effects of porcine follicular fluid in the postcastration rise of gonadotropins in the rabbit

The effects of repeated administration of porcine follicular fluid (PFF) on the follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels after castration were studied in rabbits. Steroid-free dextran-charcoal extracted PFF was administered to male and female adult rabbits at 0800 and 1600 h for four days immediately following castration. Serum levels of FSH and LH were measured before, during and after the PFF administration and compared to controls. A significant increase in FSH and LH was observed within 24 h following castration in the controls. In the PFF-treated group, a clear suppression of serum FSH levels was observed during PFF administration in both males and females. FSH concentrations returned to the control levels within 24 h after PFF withdrawal. Even through LH levels showed no differences during PFF injection, compared to controls, a significant increase was observed following discontinuation of PFF administration.     

Opioidergic control of gonadotropin secretion in the female rabbit: divergent effects of morphine on secretion of follicle-stimulating hormone and luteinizing hormone

The nature of secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was followed in female rabbits on a daily basis from age 36 to 60 days by sequential 5-min blood sampling over 1- to 2-h periods each day. Both LH and FSH were found to be secreted in a pulsatile manner. The mean LH pulse amplitude over the 25 days was 0.95 +/- 0.32 ng/mL and for FSH it was 10.15 +/- 1.11 ng/mL. Mean plasma LH levels were significantly increased from 1.46 +/- 0.08 ng/mL in 36 to 42-day-old rabbits to 1.89 +/- 0.12 ng/mL in 43 to 50-day-old rabbits and remained elevated from 50 to 60 days. FSH levels during the same periods also rose significantly from 14.93 +/- 0.79 to 19.57 +/- 2.05 ng/mL. To examine the influence of endogenous opioid peptides on the release of LH and FSH in 36 to 60-day-old female rabbits, morphine sulfate at 0.2, 0.5, 2.0, and 5.0 mg/kg was administered subcutaneously after 30 min baseline sampling, and blood was taken for another 60-120 min. Morphine at all doses and at all ages inhibited the amplitude and frequency of LH pulses but had no effect on FSH secretion. To determine whether the effects of morphine on LH secretion could be reversed with naloxone, females aged 82-114 days were used. Naloxone administered 1 h after morphine reversed the inhibitory effects of morphine, whereas the simultaneous administration of naloxone with morphine had variable effects but seemed to delay the LH increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of the perinatal steroid environment on three sexually dimorphic parameters of the rat brain

Gonadectomy of male rats was performed at 0, 6-7 (6h), 12-13 (12h), or 24 h postnatally in order to examine the influence of testosterone exposure on sexual differentiation of the brain. The indices examined were: the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) titers following estradiol benzoate (EB) and progesterone (P) administration. Control animals were sham-operated at 0 h and gonadectomized at 29 days of age (sham). A decrease in the percentage of males with elevated plasma LH levels following P was found with increasing delay before gonadectomy. Significant (P less than 0.001) differences existed in the amplitude of plasma LH titers 5 h following P administration between sham, 0 h, and 6 h groups. Follicle-stimulating hormone was also elevated in all neonatally gonadectomized male groups following P administration, but there was no difference between the groups. Volume of the SDN-POA was significantly (P less than 0.001) smaller in all gonadectomized males when compared to that of sham-operated males, but no differences existed between males gonadectomized at the different hours postpartum. In female rats gonadectomized at 0 h (F0h), LH levels were elevated 5 h following P, but only to a magnitude of 36% of that of sham-operated controls (P less than 0.001). Volume of the SDN-POA of the F0h group was significantly reduced (P less than 0.05) when compared to that of sham females. Thus, in males, the presence of the tests prenatally may be responsible for the initiation of masculinization of LH release mechanisms and the SDN-POA, but both require further androgen exposure for their completion. In addition, the LH and FSH regulating systems show a differential sensitivity to the steroid hormone environment during development that shapes the animal's response to steroid as an adult.