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 lithium on the pituitary-gonadal axis in the rat: evidence for dose-dependent changes in plasma gonadotropin and testosterone levels

The purpose of the present study was to examine the effects of lithium, a drug which is now used rather widely in the treatment of acute mania and the prophylaxis of manic-depressive bipolar disorders, on the pituitary-gonadal function in the laboratory rat. Sexually adult male rats, maintained under standardized laboratory conditions (LD 14: 10; lights on at 06:00 h, CST), were injected (ip) with lithium chloride both acutely for 1 day and chronically for 5 days, and by utilizing a low and high dose. For the low dose, lithium was injected twice daily (at 10:00 and 15:00 h) at 2.5 meg/Kg for 1 and 5 days, whereas in the high dose groups, also receiving lithium twice daily and at the same hours, the dosages were 5 meq/Kg for 1 day and 3.5 meq/Kg for 5 days. Animals were sacrificed 4 hours after the last lithium (or saline) injections. Plasma and pituitary levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and plasma levels of testosterone (T) were measured by radioimmunoassay (RIA). The administration of the low dose led to a significantly higher (P less than 0.001) plasma FSH, but unaltered plasma LH, levels after 5 days. In contrast, the high dose lithium led to significant suppressions of plasma LH (P less than 0.02; on day 5) and FSH (P less than 0.001; on both day 1 and 5) levels. The levels of plasma T also showed a significant reduction following the low dose (P less than 0.02; on day 5), as well as the high dose lithium treatment, as evident after both 1 (P less than 0.02) and 5 (P less than 0.02) days. Regardless of the dosage, or the duration of treatment, pituitary gonadotropin levels remained unaltered following lithium. The results of our present experiments suggest that lithium administration, either acutely or on a chronic basis, might be associated with significant adverse effects on the pituitary-testicular axis. Furthermore, since some of the hormonal changes were evident when plasma lithium concentration was within the therapeutic range, our data may have potential clinical implications.     

Lithium: evidence for reduction in circulating testosterone levels in mice following chronic administration

Lithium, the widely-used antipsychotic drug, is known to exert adverse effects on a number of endocrine organs. In the present investigations, the effects of chronic lithium administration on circulating levels of testosterone and plasma and pituitary levels of luteinizing hormone (LH) were evaluated in order to examine whether or not the pituitary-gonadal axis is a probable target of lithium action. Adult male C57BL/6 mice, maintained on a fixed photoperiodism (LD 14:10), were administered lithium orally, by being fed on a specially prepared chow containing 0.4% lithium chloride for 15 or 30 days, while their matched controls were maintained on standard laboratory chow. At the termination of the respective experimental schedules, the animals were decapitated, their blood collected, and plasma was separated and stored frozen. Pituitaries were quickly removed, weighed, homogenized, centrifuged and their supernatants were stored frozen. Testosterone in plasma and LH in pituitary and plasma were quantitated by standard RIA methods. Plasma Li concentration was determined by using flame photometric methods. A significant suppression in testosterone levels was noted after both 15 (p less than .01) and 30 (p less than .05) days of lithium treatment, but both pituitary and plasma LH levels remained unchanged at both the periods. It is, therefore, suggested that lithium exerts its effect directly at the level of the Leydig cells rather than through the pituitary-gonadal axis. Since the noted lithium-induced reduction of testosterone was manifested when the plasma lithium levels were within (or around) the therapeutic range, these results may have important clinical implications.     

Effects of lithium chloride on testicular steroidogenic and gametogenic functions in mature male albino rats

The present study was undertaken to evaluate the effects of lithium, an antimanic drug, on steroidogenic and gametogenic functions of testis in the laboratory rat. Adult male rats of Wistar strain maintained under standard laboratory conditions (L:D, 14h:10h), were injected (S.C) with lithium chloride at the dose of 0.1 mg, 0.2 mg and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta hydroxysteroid dehydrogenase (17 beta-HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100 g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular delta 5-3 beta-HSD, 17 beta-HSD activities and gametogenesis. In contrast, 0.2 mg of lithium treatment for 21 days causes a significant reduction of plasma FSH (P less than 0.01), LH (P less than 0.001), PRL (P less than 0.001) and T (P less than 0.001) along with inhibition of testicular delta 5-3 beta-HSD activity (P less than 0.01) and 17 beta-HSD activity (P less than 0.001). Gametogenic activity does not exhibits any significant reduction in the number of preleptotene spermatocytes (PLSc) and midpachytene spermatocytes (mPSC) while significant reduction in the number of spermatogonia A (Asg) (P less than 0.01) and Step 7 spermatids (7Sd) (P less than 0.001) were observed at stage VII of seminiferous cycle when compared to control. The degree of detrimental effects of lithium on testicular activity became more prominent at the dose of 0.4 mg/100 g body wt. The results of our experiments suggest that lithium administration might be associated with significant adverse effects on testicular activities. Furthermore, since hormonal changes and altered gametogenic activities were evident when plasma lithium concentration was below or within the therapeutic range, our data may have some potential clinical implications.     

Effect of lithium chloride on spermatogenesis and testicular steroidogenesis in mature albino rats: duration dependent response.

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7 Sd) along with Leydig cell nuclear area (LCNA) and radioimmunoassay of plasma levels of gonadotropins (FSH and LH), prolactin (PRL) and testosterone (T), activities of testicular, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were measured in mature rats of the Wistar strain following treatment with lithium chloride at a dose of 200 ug/100 g body wt/day for 7,14 and 21 days. A remarkable reduction in plasma levels of FSH (P less than 0.001), LH (P less than 0.05, P less than 0.01), PRL (P less than 0.05, P less than 0.001) and T (P less than 0.001) along with significant diminution in the activities of testicular delta 5-3 beta-HSD (P less than 0.001) and 17 beta-HSD (P less than 0.001) were observed following lithium treatment for 14 and 21 days. 21 days of treatment also resulted a marked degree of degeneration of ASg (P less than 0.05) and 7Sd(P less than 0.001) at stage VII but 14 days of treatment did not exhibited any significant effect on testicular gametogenesis. LCNA was decreased after lithium chloride treatment for 14 and 21 days (P less than 0.001). 7 days of treatment did not exert any notable result in the above parameters. The results of our experiment suggest that duration of lithium treatment is the critical factor for its adverse effects on testicular activity when the plasma levels of lithium remain within the therapeutic range. The possibility of an indirect action of lithium at the level of the testes is also discussed. Hence the data of our experiments have potential clinical implication.     

Analysis of androgen action on pituitary gonadotropin and prolactin secretion in ewes

To study the role of androgens in the control of gonadotropin and prolactin secretion in ther ewe, we have characterized androgen receptors in pituitary cytosol, and investigated the effect of androgens on pituitary hormone release in vivo and in vitro. High affinity, low capacity receptors, with an affinity for methyltrienolone (R1881) greater than 5 alpha-dihydrotestosterone (5 alpha-DHT) greater than testosterone (T) much greater than androstenedione (A4), estradiol-17 beta (E2) and progesterone (P), were identified in pituitary cytosol. Addition of 1 nM 5 alpha-DHT, but not A4, inhibited luteinizing hormone (LH) release from pituitary cells in vitro, induced by 10(10) to 10(-7) M luteinizing hormone releasing hormone (LHRH). The release of follicle-stimulating hormone (FSH) with 10(-9) M LHRH was inhibited when cells were incubated with 1 nM 5 alpha-DHT. 5 alpha-DHT had no effect when higher or lower doses of LHRH were used. In ovariectomized ewes, neither an i.v. injection of 1 mg, nor intracarotid injections of up to 1 mg, 5 alpha-DHT affected plasma LH, FSH or prolactin levels, despite dose-related increases in plasma 5 alpha-DHT levels. Daily or twice daily i.m. injections of 5 mg 5 alpha-DHT in oil did not affect LH or FSH levels, but daily injections of 20 mg significantly reduced plasma LH levels within 4 days and plasma FSH levels within 6 days. Thus, despite the presence of androgen receptors in the ewe pituitary, we conclude that androgens per se are of minimal importance in the regulation of pituitary LH, FSH and prolactin secretion in the ewe. The low binding affinity of A4 and the lack of its effect on hormone secretion in vitro suggests that A4 may act as an estrogen precursor rather than an androgenic hormone. The function of the pituitary androgen receptor remains to be established.     

Transitory increase in plasma FSH and LH levels induces early vaginal opening and corpus luteum formation in ovarian transplants of rats ovariectomized at 20 days of age

The effect of a transitory increase in plasma FSH and LH levels on puberty has been investigated. Hormonal changes were induced by bilateral ovariectomy (OVX) at 20 days of age followed by implantation of two ovaries (donor animals 20-day-old) beneath the kidney capsule 1, 2 or 3 days later. In an other group of animals the two interventions were made in reversed order. Rats in which OVX was made first showed early vaginal opening. If ovarian implantation preceded OVX, these two interventions did not affect the time of vaginal opening. More than 1/3 of the ovarian implanted animals exhibiting early opening of the vagina contained corpora lutea three days after vaginal opening. FSH and LH levels of OVX + ovary implanted rats were from the third day on following implantations markedly different from the OVX controls and were in the range of intact or sham-operated rats. The present findings indicate that a transitory increase in plasma gonadotropin levels around twenty days of age may lead to precocious puberty.     

Effects of x-ray irradiation on the subsequent gonadotropin secretion in normal and neonatally estrogenized female rats.

Female rats were irradiated with 190R of X-rays at 10 days of age and sacrificed 4, 7 or 12 months later. Their ovaries were histologically examined and serum levels and pituitary contents of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. Both serum levels and pituitary contents of LH and FSH rose significantly 4 and 7 months after irradiation, although the ovaries were markedly reduced in weight. On the contrary, 12 months after irradiation, the ovaries increased in weight and consisted mostly of polyhedral, hyperplastic interstitial cell masses, and both LH and FSH in the serum and pituitary were reduced to normal levels. These characteristic changes in the ovarian weight and histological appearance could not be observed in the similarly irradiated animals which were received daily injections of estrone for the first 30 days of postnatal life, i.e., daily injections of 50 mug for the first 10 days, 100 mug for the middle 10 days and 200 mug for the last 10 days. Serum LH levels of the estrogenized irradiated rats at 7 or 12 months of age did not elevate although those of FSH were significantly higher than the non-irradiated intact levels. From these results, a rise in the blood levels of LH and the FSH may be attributed to the increase in weight and the histological changes in the ovaries of the irradiated female rats, and the elevation of only FSh level may not result in the abnormal growth of the irradiated ovaries.     

Effects of steroid administration on pituitary luteinizing hormone and follicle-stimulating hormone in ovariectomized pony mares in the early spring: pituitary responsiveness to gonadotropin-releasing hormone and pituitary gonadotropin content

These experiments tested the hypothesis that administration of steroid hormones to ovariectomized (OVX) mares during the vernal transition to the breeding season would influence LH and FSH secretion. Circulating gonadotropin concentrations, response to exogenous GnRH, and pituitary gonadotropin content were monitored. Experiments 1 and 2 were conducted, beginning 10 March, and 3 February, respectively, utilizing a total of 30 long-term OVX pony mares. In experiment 1, mares were administered vehicle (n = 5) or estradiol-17 beta (E2, n = 5, 5 mg/3 ml sesame oil), twice daily for 16 days. Blood samples were collected daily for assessment of circulating LH and FSH concentrations. On Day 10 of treatment, 400 micrograms GnRH were administered to all mares. LH increased significantly over days of treatment in the estradiol-treated group, but pituitary response to GnRH tended to be less than in control mares. Circulating FSH tended to decline over days of treatment in estradiol-treated mares, and the pituitary response to GnRH was significantly reduced. Pituitary LH, but not FSH, was increased on Day 16 of treatment with estradiol. In experiment 2, 20 OVX mares received, twice daily, vehicle (n = 5), E2, n = 5; 5 mg), progesterone (P4, n = 5; 100 mg), or progesterone plus estradiol (P4/E2, n = 5; 100 + 5 mg). Treatment continued for 14 days. GnRH (100 micrograms) challenges were administered on Days 6 and 13 of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of gastric inhibitory polypeptide (GIP) on the release of anterior pituitary hormones

Several members of the secretin family of hormones have been demonstrated to alter anterior pituitary hormone secretion. Here we report the action of gastric inhibitory polypeptide (GIP) on gonadotropin and somatotropin release. Intraventricular injection of 1 microgram (0.2 nmole) GIP (2.5 microliters) produced a significant decrease in plasma FSH at 30 (p less than 0.02) and 60 min after its injection (p less than 0.01). The FSH-lowering effect of a higher dose of 5 micrograms (1 nmole) of GIP was already developed at 15 min (p less than 0.01) and was prolonged until the end of the experiment (60 min, p less than 0.05). No change in plasma LH was detected at any time during the experimental period. If 5 micrograms of estradiol-benzoate were given SC 48 hr prior to experiment, the initial values of FSH and LH were markedly decreased. In these animals GIP failed to influence plasma FSH and LH. When dispersed anterior pituitary cells from OVX rats were cultured overnight and incubated in vitro with GIP, the peptide was found to induce both FSH and LH release. Highly significant release occurred with the lowest dose tested of 10(-7) M and there was a dose-response effect for both hormones. The slope of the dose-response curve was similar for both FSH and LH release. GIP was less potent than LHRH which produced a greater stimulation of both FSH and LH release at a dose of 10(-9) M than did 10(-7) M GIP. The two peptides had an additive effect on the release of both FSH and LH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen (EB) and EB + progesterone (P) induced changes in pituitary sodium, potassium adenosine triphosphatase activity (ATPase).

Estradiol-benzoate (EB) injected into previously ovariectomized (OVX) rats, increased pituitary ATPase activity 69% over controls, within one hour of treatment. Twelve hours after injection, ATPase activity was not significantly different from controls. Progesterone [(P): 5mg/100gBW] administered in conjunction with EB elicited an analogous response. AT at time of EB and EB+P induced increments in pituitary ATPase activity, plasma LH levels were dramatically reduced to normal, intact diestrous control levels. Post-castrational elevations in FSH were also suppressed after one hour of treatment with EB, but not following EB+P administration. The results suggest that the inhibitory actions of EB and EB+P on post-castrational LH levels may be related to modulation by these steroids of pituitary membrane ATPase activity.     

Influence of intracerebroventricular (ICV) injection of ACTH (1-24) on plasma gonadotropin in female rats: dose-response study

The intracerebroventricular (ICV) injection of ACTH (1-24) (0.1, 1.0 and 2.5 micrograms) to adult conscious ovariectomized (OVX) rats caused a dose-related inhibition of plasma LH at 10 min postinjection. The ICV injection of ACTH (1-24) (2.5 micrograms) to OVX rats in the absence or presence of a single dose of estradiol benzoate (OVX + EB): a) Decreased significantly plasma LH levels in OVX rats at 10 and 30 min postinjection. b) Decreased significantly plasma LH levels in (OVX + EB) rats at 10 min but not at 30 min postinjection. c) Did not change plasma FSH levels at 10 or 30 min postinjection in both (OVX) or (OVX + EB) rats. d) Did not change plasma ACTH levels at 10 or 30 min postinjection in (OVX) rats. Our observation suggest that ACTH (1-24) inhibited plasma LH, possibly through brain sites of action.     

Short-term effects of vasoligation upon plasma follicle-stimulating hormone, luteinizing hormone, and prolactin in the adult rat: further evidence for a direct neural connection between the testes and the central nervous system

The purpose of these experiments was to determine whether bilateral vasoligation of adult male rats had any short-term effects upon plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Adult male rats (250-300 g) were either bilaterally vasoligated or sham vasoligated, and blood samples were obtained by cardiac puncture preoperatively and at 24 h and 7 days following surgery. Plasma levels of both FSH and LH were significantly (P less than 0.01) decreased at 24 h following vasoligation compared to preoperative levels and those of sham-operated controls. However, the response was differential since, at 7 days following vasoligation, plasma FSH was still significantly decreased while LH was returning to control levels. Conversely, plasma prolactin levels were significantly (P less than 0.01) increased at 24 h compared to preoperative values and those in sham-operated controls, and at 7 days prolactin had returned to preoperative control levels. Sham vasoligation did not significantly change plasma levels of FSH, LH, or prolactin at any of the time intervals investigated. These results provide further evidence that suggests that there may be a direct connection between the testis and central nervous system that may be involved in the short-term regulation of gonadotropin and prolactin secretion.     

The influence of feed restriction and subsequent re-feeding on gonadotrophin secretion and serum testosterone levels in male rats.

Male rats at 3 months were fully fed or were restricted to 50% of normal feed intake for 10 or 20 days. Underfeeding for either period resulted in reduced (P less than 0-05) body weight and pituitary weight but did not affect testicular weight. Underfeeding for 20 days resulted in reduced (P less than 0-05) weights of the seminal vesicles and ventral prostate. The serum concentration of LH was depressed (P less than 0-05) after 10 days of underfeeding and the pituitary concentration of LH was elevated (P less than 0-05) after 20 days of underfeeding. Neither serum nor pituitary concentration of FSH was influenced by feed level. Serum testosterone concentration was reduced in rats underfed for 20 days. In a second study, 2-month-old males were fully fed, underfed (15 days) or underfed and then re-fed (full feed) for 1, 2, 3 or 7 days. Underfeeding produced effects similar to those noted in the first experiment. Re-feeding of underfed rats resulted in body and ventral prostate weights returning to levels similar to those of fully fed controls by Day 7. The serum level of FSH was elevated (P less than 0-05) above the control level on Days 1, 3 and 7 of re-feeding, while the serum level of LH appeared to return to the control level. Serum testosterone level rebounded and exceeded (P less than 0-05) the control level on Days 1 and 2 of re-feeding.     

Effect of CRF in the median eminence on gonadotropin levels in conscious female rats

To evaluate whether the median eminence (ME) is the site of action of CRF (corticotropin releasing factor) in inhibiting LH levels in female rats, we have injected CRF (1 nmol) directly into the ME and then measured plasma LH and FSH concentrations in conscious ovariectomized (OVX) rats in the absence or presence of a single dose of estradiol benzoate (EB). CRF caused a significant decrease in plasma LH levels in both OVX and OVX + EB rats at 30 min postinjection, in comparison to the values obtained in animals injected with water only. Injection into the ME of water had no effect on plasma LH levels in either OVX or OVX + EB animals. The results suggest that CRF probably inhibits LH secretion, at least in part by a central action on GnRH release in ME.     

Pituitary luteinizing hormone-releasing hormone receptors in ovariectomized cows after challenge with ovarian steroids

Acute changes of bovine pituitary luteinizing hormone-releasing hormone (LHRH) receptors in response to steroid challenges have not been documented. To investigate these changes 96 ovariectomized (OVX) cows were randomly allotted to one of the following treatments: 1) 1 mg estriol (E3); 2) 1 mg 17 beta-estradiol (E2); or 3) 25 mg progesterone (P) twice daily for 7 days before 1 mg E2 and continuing to the end of the experiment. Serum was collected at hourly intervals from 4 animals in each group for 28 h following estrogen treatment. Four animals from each treatment were killed at 4-h intervals from 0 to 28 h after estrogen injection to recover pituitaries and hypothalami. Treatment with E3 or E2 decreased serum luteinizing hormone (LH) within 3 h and was followed by surges of LH that were temporally and quantitatively similar (P greater than 0.05). Progesterone did not block the decline in serum LH, but did prevent (P less than 0.05) the E2-induced surge of LH. Serum follicle-stimulating hormone (FSH) was unaffected (P less than 0.05) by treatment. Pituitary concentrations of LH and FSH were maximal (P less than 0.001) at 16 h for E3 and 20 h for E2, whereas P prevented (P greater than 0.05) the pituitary gonadotropin increase. Concentrations of LHRH in the hypothalamus were similar (P greater than 0.05) among treatments. Pituitary concentrations of receptors for LHRH were maximal (P less than 0.005) 12 h after estrogen injection (approximately 8 h before the LH surge), even in the presence of P. This study demonstrated that in the OVX cow: 1) E2 and E3 increased the concentration of receptors for LHRH and this increase occurred before the surge of LH; and 2) P did not block the E2-induced increase in pituitary receptors for LHRH but did prevent the surge of LH.     

Intrahypothalamic action of corticotrophin-releasing factor (CRF) to inhibit growth hormone and LH release in the rat

The effects of intravenous or intraventricular injection of synthetic ovine corticotrophin-releasing factor (oCRF) on plasma levels of anterior pituitary hormones were studied in conscious, ovariectomized (OVX) female rats and compared with the actions of the peptide on dispersed anterior pituitary cells from OVX female rats incubated in the presence of CRF. Third ventricular injection of oCRF in freely moving rats caused a significant increase in plasma levels of ACTH in a dose-related manner with a minimal effective dose of less than 0.5 micrograms (0.1 nmol). The effect was observable at 5 min after injection and persisted for the 60 min duration of the experiment. In contrast, growth hormone levels were significantly depressed within 15 min with a minimal effective intraventricular dose of 0.5 micrograms. The suppression persisted for the duration of the experiment but there was no additional effect of the higher dose of 5 micrograms. Plasma LH levels were also lowered by the highest dose of 5 micrograms (1.0 nmol) of oCRF, with the first significant lowering at 30 min. Lower doses had no effect on plasma LH. Plasma TSH levels were not significantly altered. Control injections of the 0.9% NaCl diluent were without effect on the levels of any of the hormones. Intravenous injection of similar doses of oCRF had no effect on plasma levels of GH or LH. The ACTH-releasing action of the oCRF preparation was confirmed by in vitro incubation of the peptide with dispersed anterior pituitary cells for 2 h. A dose-related release of ACTH occurred in doses ranging from 0.1-10 nM, but there were no effects on the release of the other anterior pituitary hormones. The results suggest that oCRF may act within the hypothalamus to suppress the release of GH and to a lesser extent LH. The stimulation of ACTH release following intraventricular CRF is presumably related to its uptake by portal blood vessels with delivery to the pituitary and stimulation of the corticotrophs.     

Dynamic changes in the gonadotrope cell subpopulations during an estradiol-induced surge in the ewe

Whether estradiol targets a subpopulation of gonadotrope cells was investigated in this study. Ovariectomized ewes (OVX) or OVX ewes immunized against GnRH and treated with hourly pulses of GnRH analogue (OVX-IMG) were killed at 6, 12, 16, and 24 h after administration of 50 microg of 17beta-estradiol (E(2)). Control ewes received no E(2) treatment. In OVX or OVX-IMG ewes killed 6 h after E(2) injection, a decrease in gonadotropin plasma levels was observed compared with non-E(2)-treated ewes. In contrast, a surge in gonadotropin plasma concentrations occurred in ewes killed 16 h after injection. The percentage of total immunoreactive gonadotrope cells among the pituitary cells was lower in E(2)-treated ewes compared with nontreated animals. The proportion of monohormonal LH cells was constant throughout the experiment, except at the surge peak, where it was enhanced. In the OVX ewes, the proportion of bihormonal LH/FSH cells was lower in the E(2)-treated ewes compared to the nontreated ewes (P: < 0.001), with a more pronounced decrease 16 h after E(2) injection. A slight increase occurred 12 h after E(2) injection compared with 6 h after injection (P: < 0.05). A similar pattern was observed in the OVX-IMG ewes, except at 12 h after E(2) injection, when no increase occurred. In both OVX and OVX-IMG ewes, injection of E(2) decreased FSHbeta mRNA expression but did not alter the relative levels of LHbeta mRNA. These data suggest that the negative feedback of E(2) on LH and FSH secretion mainly targets the bihormonal cells and occurs, at least in part, directly at the pituitary level. During the gonadotropin surge, the sustained FSH release from the bihormonal cells would induce a switch from bihormonal cells to monohormonal LH cells by depleting these cells of FSH.     

Preliminary observations on the existing relationship between plasma levels of prolactin and hypophyseal reserves of FSH and LH in the male

PRL plasma levels and FSH and LH pituitary reserve were tested in ten apparently healthy male subjects. A good correlation was found between PRL on one hand and FSH plasma levels (p less than 0,05), LH plasma levels (p less than 0,01) and FSH pituitary reserve (p less than 0,01) on the other hand. This seems to support the current hypothesis that prolactin may cause a progressive clinically latent impairment in the spermatogenetic function of the testis. Further evidence is needed.     

Effects of ovine follicular fluid on plasma LH and FSH secretion in ovariectomized ewes to indicate the site of action of inhibin

Ovariectomized ewes were given 2 ml s.c. injections of ovine follicular fluid (oFF) (N = 3) or serum (N = 3) and blood samples were collected each day for 3 days. Follicular fluid caused a significant (P less than 0.005) reduction in FSH within 1 day, but did not affect mean LH values. Two groups of 3 ewes were treated as above but sampled intensively (each 10 min for 6 h) on Days 1 (before treatment) and 4; mean plasma FSH concentration and plasma LH pulse frequency and amplitude were ascertained. Significant (P less than 0.005) reduction of FSH concentration was seen in the oFF-treated ewes. A non-specific reduction in LH pulse amplitude, but not pulse frequency, was noted in the control ewes. This experiment was repeated with 2 groups of 4 ewes that were conditioned to the experimental environment and effects on LH secretion were not observed in the controls given serum. Treatment with oFF caused a 70% reduction (P less than 0.005) in plasma FSH and a small (30%) but significant (P less than 0.005) reduction in mean LH concentrations. The latter was probably associated with a reduction in LH pulse amplitude in 3/4 animals (N.S.) with no change in LH pulse frequency. Treatment with oFF, as in Exp. 1, caused a 95% reduction in FSH values and significant (P less than 0.01) reduction (32%) of LH pulse amplitude in ovariectomized ewes that had been subjected to hypothalamo-pituitary disconnection and in which gonadotrophin secretion was reinstated with pulses of 250 ng GnRH every 2 h. These results suggest that proteins from the sheep follicular fluid, including inhibin, act at the pituitary level to inhibit FSH secretion and may have some effects on LH pulse amplitude.