Stress induced changes in testis function

The mechanism through which chronic stress inhibits the hypothalamic-pituitary-testicular axis has been investigated. Chronic restraint stress decreases testosterone secretion, an effect that is associated with a decrease in plasma gonadotropin levels. In chronically stressed rats there was a decrease in hypothalamic luteinizing hormone-releasing hormone (LHRH) content and the response on plasma gonadotropins to LHRH administration was enhanced. Thus the inhibitory effect of chronic stress on plasma LH and FSH levels seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a modification in LHRH secretion. It has been suggested that beta-endorphin might interfere with hypothalamic LHRH secretion during stress. Chronic immobilization did not modify hypothalamic beta-endorphin, while an increase in pituitary beta-endorphin secretion was observed. Since we cannot exclude that changes in beta-endorphin secreted by the pituitary or other opioids may play some role in the stress-induced decrease in LHRH secretion, the effect of naltrexone administration on plasma gonadotropin was studied in chronically stressed rats. Naltrexone treatment did not modify the decrease in plasma concentrations of LH or FSH. These findings suggest that the inhibitory effect of restraint on the testicular axis is exerted at hypothalamic level by some mechanism other than opioids.     

Adenohypophyseal hormone response to chronic stress in dexamethasone-treated rats.

The influence of dexamethasone treatment on the basal values of corticosterone, GH, prolactin (PRL), LH and FSH, as well as on the adenohypophyseal hormone response to chronic stress was studied in female rats. Dexamethasone acetate (25 micrograms/100 b.w.), given by gavage twice daily for 10 days, decreased the resting plasma levels of corticosterone, GH, LH and PRL, whereas the FSH titers remained normal. The secretion of ACTH (evaluated indirectly through corticosterone concentrations) and of GH appeared to be most sensitive to the suppressive effect of dexamethasone. The same hormonal response pattern was induced by 8 h of daily immobilization for 10 days, except that ACTH release was enhanced and the plasma LH titers dropped more drastically. Dexamethasone administration in combination with restraint did not alter the characteristic hormonal profile of chronic stress, despite the fact that ACTH secretion was completely blocked. These data suggest that the inhibition of PRL, LH and GH secretion following severe, chronic stress is not causally related to the sustained elevation of plasma ACTH.     

Effects of restraint stress on plasma LH and testosterone concentrations, Leydig cell LH/hCG receptors, and in vitro testicular steroidogenesis in adult rats

We examined the effect of restraint stress (3 hr) on plasma LH and testosterone levels, on the Leydig cell LH/hCG receptor, and on the activity of enzymes in the testicular steroidogenic pathway of the adult rat. Restraint stress caused a 47% reduction in plasma testosterone concentrations, but had no effect on plasma LH levels. The binding capacity and affinity of Leydig cell LH/hCG receptors were not affected by restraint. Stress did not affect the testicular activity of 20,22 desmolase or 3 beta-hydroxysteroid dehydrogenase, but testicular interstitial cells of stressed rats incubated in vitro with progesterone as a substrate produced more 17 alpha-hydroxyprogesterone but less testosterone than control cells, and when incubated with 17 alpha-hydroxypregnenolone, produced 39% less androstenedione and 40% less testosterone than control cells. These results suggest that restraint stress inhibited 17,20 desmolase but not 17 alpha-hydroxylase activity. When the delta 4 pathway was blocked with cyanoketone (3 beta-HSD inhibitor), stress did not alter the production of pregnenolone or 17 alpha-hydroxypregnenolone, but the production of dehydroepiandrosterone by cells from stressed rats was subnormal, suggesting again a reduction of 17,20 desmolase activity. The data suggest that a major site of the inhibitory action of restraint stress on testicular steroidogenesis is the 17,20 desmolase step. The disruption of androgen production by restraint appears to be LH independent since stress did not affect plasma LH levels, the binding capacity or affinity of LH/hCG receptors, or the activity of 20,22 desmolase.     

Stress-induced testicular hyposensitivity to gonadotropin in rats. Role of the pituitary gland

The time course of stress-induced testicular hyposensitivity to gonadotropins was studied in hypophysectomized or naloxone-treated rats exposed to various periods of immobilization. Blood was collected from a chronically indwelling intra-atrial catheter every hour for luteinizing hormone (LH) and testosterone (T) measurement. Eight hours of immobilization completely suppressed T secretion without significant effect on LH. Human chorionic gonadotropin (hCG, 5 IU/rat, i.m.) induced a marked increase in plasma T levels in normal control groups 3 h post-injection while in immobilized rats the response was completely abolished, even after only 30 min of stress. In hypophysectomized rats, as expected, plasma T levels were undetectable, but, contrary to results obtained in normal animals, hCG induced a similar increase of plasma T levels both in control and stressed rats. Immobilization stress failed to inhibit plasma T values in hypophysectomized rats pretreated for 4 days with human menopausal gonadotropin (hMG) + hCG, while it did so in similarly treated normal animals. Naloxone induced a rise of plasma LH and T levels in control rats, but did not antagonize the stress-induced fall of plasma T concentration. In all groups, steroid testicular content mimicked variations of plasma T values. In particular, in stressed animals the lack of accumulation of testicular 17-hydroxyprogesterone probably reflected a normal activity of 17-20 lyase. These results indicate that stress induces very rapidly a state of Leydig cell hyposensitivity to gonadotropins and a blockade of T biosynthesis. The causal relationship between the two effects is presently not clear but these events seem to be due to stress-induced release of an inhibitory factor of pituitary origin other that endorphin.     

Divergent regulation of gonadotropin subunit mRNA levels by androgens in the female rat.

To examine the effects of gonadal steroids on the pretranslational regulation of the gonadotropin subunits in the female, adult female rats, beginning 7 or 28 days after ovariectomy, received daily injections of testosterone propionate (T), dihydrotestosterone propionate (D), or estradiol benzoate (E) for 7 days. Intact cycling females and ovariectomized rats that received vehicle served as controls. Serum was obtained for LH and FSH levels to assess changes in gonadotropin secretion. Total RNA from individual rats was recovered and analyzed by blot hybridization with specific radiolabeled cDNA probes for the alpha, LH beta, and FSH beta subunits. Autoradiographic bands were quantitated and standardized to mRNA levels in the intact animals. Ovariectomy resulted in a rise in serum gonadotropin levels and all three gonadotropin subunit mRNA levels. Estrogen replacement resulted in suppression of alpha, LH beta, and FSH beta mRNAs whether given at 7 or 28 days after ovariectomy. In contrast, whereas androgen replacement decreased alpha and LH beta mRNAs, D or T did not consistently suppress FSH beta mRNAs. We conclude that chronic estrogen administration to the castrated female rat uniformly suppresses all three gonadotropin subunit mRNA levels. In female rats, as in male rats, chronic androgen administration fails to negatively regulate FSH beta mRNAs.     

Triiodothyronine (T3) modulation of gonadotropin secretion in the female rat.

The effect of T3 upon gonadotropin secretion was examined in ovariectomized (Ovarx), Ovarx thyro-parathyroidectomized (Ovarx-TxPx), or proestrus rats. T3 (50 microgram/-100 gBW), administered late diestrus-2, abolished the LH surge during the critical period of proestrus in 7 out of 9 rats; the rise in sera FSH was not inhibited, although a distinct peak was absent. Administration of 5 or 50 microgram T3/100gBW 2.5h before the critical period resulted in either a suppression or an alteration of the timing of LH release. In the 5 microgram T3/100gBW treated animals the sera FSH peak was delayed in timing, whereas in the 50 microgram T3/100gBW treated rats sera FSH demonstrated two separate peaks during the critical period. Treatment with various dosages of T3 of Ovarx-TxPx rats resulted in significant suppressions (p less than 0.05) of sera LH and FSH. Despite depressed concentrations of sera LH and FSH in T3-treated rats pituitary sensitivity to a challenge of 3LHRH was enhanced. Hence, the pituitary was not the site of T3 inhibition of gonadotropin secretion. Additionally, T3 did not modify pituitary LH content or hypothalamic LH3 releasing activity (LHRH). Since T3 did not inhibit gonadotropin secretion at the pituitary level, a neural site of T3 action is suggested.     

The inhibitory action of corticotropin-releasing hormone on gonadotropin secretion in the ovariectomized rhesus monkey is not mediated by adrenocorticotropic hormone

Earlier observations in our laboratory indicated that i.v. infusion of human/rat corticotropin-releasing hormone (hCRH) suppresses pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in ovariectomized rhesus monkeys. Since cortisol secretion increased significantly as well, it was not possible to exclude the possibility that this inhibitory effect of hCRH on gonadotropins was related to the activation of the pituitary/adrenal axis. The purpose of the present study was to determine the role of pituitary/adrenal activation in the effect of hCRH on LH and FSH secretion. We compared the effects of 5-h i.v. infusions of hCRH (100 micrograms/h, n = 7) and of human adrenocorticotropic hormone (ACTH) (1-24) (5 micrograms/h, n = 3; 10 micrograms/h, n = 3, 20 micrograms/h, n = 3) to ovariectomized monkeys on LH, FSH, and cortisol secretion. As expected, during the 5-h ACTH infusions, cortisol levels increased by 176-215% of baseline control, an increase similar to that observed after CRH infusion (184%). However, in contrast to the inhibitory effect observed during the CRH infusion, LH and FSH continued to be released in a pulsatile fashion during the ACTH infusions, and no decreases in gonadotropin secretion were observed. The results indicated that increases in ACTH and cortisol did not affect LH and FSH secretion and allowed us to conclude that the rapid inhibitory effect of CRH on LH and FSH pulsatile release was not mediated by activation of the pituitary/adrenal axis.     

Validation of the mechanisms proposed for the stimulatory and inhibitory effects of progesterone on gonadotropin secretion in the estrogen-primed rat: a possible role for adrenal steroids.

The stimulatory and inhibitory effects of progesterone on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion were found to be dependent on the length of estrogen exposure in ovariectomized estrogen-primed rats. Progesterone suppressed LH and FSH secretion when administered 16 hours after a single injection of estradiol to ovariectomized rats. If the estradiol treatment was extended over 40 hours by two injections of estradiol 24 hours apart, progesterone administration led to a highly significant elevation of both serum LH and FSH levels 6 hours later. In addition to the direct stimulatory effect on LH and FSH release, progesterone, when injected 1 hour before, was able to antagonize the suppressive effect of a third injection of estradiol on LH and FSH release. In the immature ovariectomized estrogen-primed rat, 10 IU of ACTH brought about a release of progesterone and corticosterone 15 minutes later and LH and FSH 6 hours later. Progesterone, but not corticosterone, appeared to be responsible for the effect of ACTH on gonadotropin release. The synthetic corticosteroid triamcinolone acetonide brought about LH and FSH release in the afternoon, while cortisol, similar to corticosterone, was unable to do so. Nevertheless, triamcinolone acetonide and cortisol brought about increased secretion of FSH the following morning.     

A role for inhibin in the control of follicle-stimulating hormone secretion in male rats

We examined the relationship of testosterone (T) and porcine follicular fluid (pFF) in the negative feedback control of FSH and LH secretion in adult male rats. Either at the time of castration (acute) or at least 30 days after castration (chronic), we implanted T-filled Silastic capsules, which were 2 mm, 10 mm, or 30 mm long; empty capsules (30 mm) served as controls. Seven days later, we injected either 0.15 ml of pFF or saline (i.v.), decapitated the rats 6 hours later, and collected trunk blood for subsequent serum analysis of FSH, LH, and T by RIA. In the acute groups, T implants suppressed the postcastration rises in plasma FSH and LH levels in a dose-dependent manner, with only the largest implant, 30 mm, able to return them to intact levels. PFF injection significantly suppressed FSH levels in intact and acute rats but had no effect on serum LH. In chronic rats, T therapy for 7 days suppressed plasma LH levels in a dose-dependent relationship, yet did not do so to plasma FSH levels. FSH levels were significantly higher in rats with the 30 mm T implants than in intact rats, but were significantly suppressed as compared to chronic controls. PFF significantly suppressed serum FSH levels in all chronic groups with the chronic controls showing the greatest amount of suppression. We conclude that the role for inhibin in the normal control of FSH secretion is that of a secondary modulator which is superimposed on, yet independent of, the steroid feedback mechanism. At any given moment this modulation is dependent upon the secretory activity of the FSH gonadotrope.     

Effects of treatment of normal and hyperprolactinemic rats with cyclosporine in vivo on the release of gonadotropins and prolactin from their pituitaries in vitro.

Cyclosporine (CyA) is extremely useful as an immunosuppressant and it is believed that at least some of its actions are due to antagonizing PRL effects. To determine whether the reported ability of CyA to inhibit gonadotropin release can be modified by PRL, we have examined the effects of treatment of normal and hyperprolactinemic rats with CyA in vivo on the release of LH, FSH and PRL from their pituitaries in vitro. Hyperprolactinemia was induced by implantation of capsules containing diethylstilbestrol (DES) and the animals were examined while the capsules were still in place (DES-IN) or after they had been removed (DES-OUT). Treatment with CyA significantly reduced plasma LH levels in control DES-IN rats without reducing basal LH release from the pituitaries of these animals in vitro. In the DES-IN rats, CyA exposure in vivo did not modify plasma PRL levels, but reduced PRL release in vitro, and interfered with the inhibitory action of dopamine (DA) on PRL release. The effect of DA on gonadotropin release in vitro was modified by CyA treatment. Administration of CyA failed to antagonize the suppressive effects of hyperprolactinemia on plasma LH and FSH levels or on the basal rates of gonadotropin release by incubated pituitaries. We conclude that CyA can reduce PRL release but does not interfere with the actions of PRL on anterior pituitary function.     

Effect of vagotomy on postcastration gonadotropin secretion in male rats

The postcastration increase in gonadotropins was studied in intact and vagotomized male rats. Rats underwent vagotomy or sham surgery immediately prior to castration. In the first experiment, rats were bled before castration and at 1, 2, 4, and 7 days after castration. Serum LH and FSH were significantly lower in vagotomized rats 1 day after castration. On days 2, 4, and 7 postcastration, serum gonadotropin levels were generally not different among experimental groups. In a second experiment, rats were decapitated at 12 or 24 hr after surgery and castration. Trunk blood was collected for assay of LH. Vagotomy had no effect on LH levels at 12 hr postcastration, but, at 24 hr postcastration, vagotomized rats had significantly lower serum LH than did sham-operated rats. These experiments indicate that vagotomy has a transient suppressive effect on gonadotropin release following castration. Such observations support the hypothesis that the vagus nerve may play a modulatory role in gonadotropin secretion.     

Acute and chronic effects of the fornix section on cyclic gonadotropin secretion and ovulation in the rat.

The fornix was sectioned in the frontal plane by means of a razor blade knife, and acute and chronic effects of this section on gonadotropin secretion were estimated. The 5-day cyclic rat which received the section of fornix under either anesthesia at 12:00 on the day of diestrus II showed advancement of the proestrous and estrous vaginal smears and as well as ovulatory gonadotropin release by one day. It was revealed that the primary effect was the inducement of FSH release on the day of section. The 4-day cyclic rat bearing the fornix section chronically resumed vaginal cyclicity after elapsing the diestrous period for 18 to 25 days. The rat ovulated normally and mean number of ova inoviducts was not different from that in the intact rat. However, the sectioned rat hadan higher concentrations of pituitary and serum FSH on the day of diestrus II than thatin the intact rat, and had an higher concentration of serum LH on the day of estrus. These results indicate that the hippocampus exerts the inhibitory influence on LH and FSH release and if this is eliminated the facilitatory influence dominates the brain mechanism controlling gonadotropin release, resulting in the advancement of estrous cycle (the acute effect) or the increase of gonadotropin release (the chronic effect).     

Pulsatile plasma profiles of FSH and LH before and during medroxyprogesterone acetate treatment in the bitch

The aim of this study was to investigate the effect of medroxyprogesterone acetate (MPA) on pulsatile secretion of gonadotropins in the bitch. Five intact Beagle bitches were treated with MPA in a dose of 10mg/kg body weight subcutaneously at intervals of 4 weeks for a total of 13 injections, starting during anestrus. The 6-h plasma profiles of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were determined before, and 3, 6, 9, and 12 months after the start of MPA treatment. After 6 months of MPA treatment basal plasma LH concentration was transiently increased significantly. Basal plasma FSH concentration and the area under the curve above the zero level (AUC0) for FSH were significantly higher after 3 months of MPA treatment than before or after 9 and 12 months of treatment. MPA treatment did not significantly affect pulse frequency, pulse amplitude, or AUC above the baseline for either LH or FSH. During treatment 58 significant LH pulses were identified, and although each LH pulse coincided with an increase in plasma FSH concentration, in 17 cases the amplitude of the increase was too small to be recognized as a significant FSH pulse. In conclusion, MPA treatment did not suppress basal plasma gonadotropin levels in the bitches. On the contrary, it caused a temporary rise in the basal concentration of both FSH and LH, which may have been due to a direct effect of MPA on the ovary. In addition, several LH pulses were not accompanied by a significant FSH pulse, suggesting that MPA treatment attenuated the pulsatile pituitary release of FSH.     

Inhibin activity and secretion of gonadotropin during the period of follicular maturation

To evaluate the relative contributions of the ovarian inhibin and estradiol-17 beta (E) on the regulation of FSH secretion, inhibin and E in ovarian venous plasma (OVP) and FSH and LH in peripheral plasma were simultaneously measured using superovulating rats with special reference to follicular maturation. By the transplantation of a pituitary gland from adult male rats under the kidney capsule between 1100 and 1200 hr on diestrus-1 in cyclic rats, superovulation was successfully induced on the morning of the next estrus without any additional treatment with human chorionic gonadotropin (hCG). The number of maturing follicles capable of ovulating in response to hCG significantly increased at 12 hours after the grafting as compared with sham-operated controls and further increases occurred until the afternoon of proestrus. In the superovulating rat, first and second surges of FSH were completely blocked and an LH surge was also partially suppressed during the periovulatory period when surges of FSH and LH were normally observed in controls. Contents of FSH as well as LH in the animal's own pituitary gland were suppressed significantly after the grafting as compared with controls. A marked increase in inhibin activity in OVP of rats with a pituitary transplant occurred concomitantly with an increase in the number of follicles capable of ovulating whereas E levels in OVP did not so. Inhibin activity in OVP at each point was much higher in the pituitary grafted rats than in controls but this was not true for E levels. These results suggest that ovarian inhibin derived from the maturing follicles rather than E may be a primary factor for regulation of FSH secretion, and high levels of endogenous inhibin can suppress synthesis of LH as well as FSH in the pituitary gland of the female rat.     

Estrogen modulates the action of nitric oxide in the medial preoptic area on luteinizing hormone and prolactin secretion

Several substances work as neuromediators of the estrogen direct and indirect (through glial cells or interneurons) action on luteinizing hormone- releasing hormone (LH-RH) neurons in medial basal hypothalamus and medial preoptic area (MPOA).Angiotensin II (AII) in the MPOA stimulates the LH and it inhibits PRL secretion in some situations. On the other hand, the effect of excitatory amino acids on LH and PRL surges during proestrus as well LH surge induced by steroids depend on nitric oxide (NO). In the present study we investigated the participation of MPOA endogenous NO on gonadotropin and PRL secretion mediated by estrogen and AII. Plasma LH, FSH and PRL was determinated in estrogen primed and unprimed ovariectomized Wistar rats that received microinjection of AII or saline into the MPOA, associated or not with a previous microinjection of an inhibitor for NOS. Our results show the following: 1 - there was no change in plasma FSH in estrogen- primed or unprimed ovarictomized related with microinjections of AII or NO antagonist in the MPOA; 2- the increase in LH secretion after ovariectomy depends on, at least in part, NO activity in the MPOA; 3- estrogen may have an indirect negative feedback action on LH-RH neurons in the MPOA through NO; 4- the stimulatory action of AII in the MPOA on LH secretion in ovariectomized rats treated with estrogen depends on NO; 5 - NO in the MPOA stimulates or inhibits PRL secretion depending on the absence or presence of estrogen, respectively; 6- the inhibitory action of AII into the MPOA on PRL secretion does not seem to depend on NO.     

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)     

Excitatory amino acid regulation of gonadotropin secretion: modulation by steroid hormones

Excitatory amino acids (EAAs) can potently modulate gonadotropin secretion in the male rat and monkey. In the present study we examined of EAAs on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the female rat under low estrogen (ovariectomized) and high estrogen (proestrus) backgrounds. In ovariectomized immature female rats (NMDA) inhibited LH but not FSH secretion at 30 min post-injection. In contrast, NMDA potently stimulated LH but not FSH secretion when administered on proestrus to adult female rats. Both glutamate and kainate were also found to stimulate LH but not FSH secretion in estrogen-treated ovariectomized immature rats. This study suggests that EAA neurotransmission may be an important component in the expression of gonadotropin surges and that EAA effects appear to be subject to gonadal steroid regulation.     

Chronic nitric oxide deficiency is associated with altered leutinizing hormone and follicle-stimulating hormone release in ovariectomized rats

Nitric oxide (NO) synthase (NOS) has been found in the gonadotrophs and folliculo-stellate cells of the anterior pituitary. Previous observations from our laboratory suggest that NO may play a role in regulating gonadotropin secretion. Because estrogen secretion by the ovary can influence gonadotropin secretion, we investigated the hypothesis that chronic in vivo NO deficiency has a direct estrogen-independent effect on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Chronic NO deficiency was induced by adding an NOS inhibitor, N-nitro-L-arginine (L-NNA, 0.6 g/l) to the drinking water of ovariectomized (OVX) rats. The control OVX rats were untreated. After 6-8 weeks, the animals were sacrificed, and the pituitaries were removed and perfused continuously for 4 hr in the presence of pulsatile gonadotropin-releasing hormone (GnRH, 500 ng/pulse) every 30 min. S-Nitroso-L-acetyl penicillamine (SNAP, an NO donor, 0.1 mM) or L-nitro-arginine methyl ester (L-NAME, an NOS inhibitor, 0.1 mM) was added to the media and perfusate samples were collected at 10-min intervals. GnRH-stimulated LH and FSH levels were significantly lower in pituitaries from OVX/NO-deficient pituitaries compared with pituitaries from the OVX control group. The addition of SNAP significantly decreased LH and FSH secretion by pituitaries from OVX control animals, but significantly increased their secretion by pituitaries from the OVX/NO-deficient animals. L-NAME also suppressed LH and FSH secretion by pituitaries from the OVX control animals and stimulated their release by pituitaries from the NO-deficient/OVX animals. Immunohistochemistry of frontal sections through the hypothalamus demonstrated that OVX/NO deficiency is associated with increased GnRH in the median eminence. We conclude that NO has a chronic stimulatory effect on LH and FSH release and the subsequent altered secretory responsiveness to NO agonist or antagonist is the result of chronic NO suppression.     

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.     

Effects of arginine vasotocin on levels of plasma gonadotropins and prolactin in ovariectomized conscious rats

Arginine vasotocin was injected into the third ventricle or intravenously in conscious, ovariectomized rats and its effect on gonadotropin and prolactin release evaluated. The peptide lowered plasma levels of both LH and prolactin in doses of 40 or 100 ng given intraventricularly. The higher dose was slightly more effective than the lower dose. Intravenous injection of a 1-microgram dose of vasotocin failed to alter plasma LH in the ovariectomized animals; however, a 5-micrograms dose induced a slight depression apparent at only 60 min following injection. Intravenous injection of 1 microgram produced a significant lowering of plasma prolactin, whereas a dramatic lowering followed the injection of the higher dose. Plasma FSH was unaffected in these experiments. Incubation of dispersed anterior pituitary cells from ovariectomized rats with various doses of vasotocin revealed no effect of the peptide on the release of FSH, LH, or prolactin. It also did not alter the response to LHRH, but it partially blocked the action of dopamine to inhibit prolactin release. The data indicate that quite low doses of arginine vasotocin act within the brain to inhibit LH and prolactin secretion in ovariectomized, conscious animals.