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.     

New data on luteotropic mechanism of action of estrogens during the rat estrus cycle]

An increase in peripheral blood progesterone concentration was observed in diestrus II, at 17:30 in 4-day cyclic female rats subcutaneously injected with 10 microgram estradiol benzoate (EB) at 10:00-11:00 on diestrus I. Pentobarbital injection (30 mg/kg) at 13:30 on diestrus II did not prevent this effect on EB. By contrast PB injected at 13:30 on diestrus II as above completely suppressed the luteinizing or ovulating effects of EB. The action of estrogen on blood progesterone level was therefore concluded to be unrelated to the mechanisms underlying estrogen-induced ovulation luteinization in the cyclic female rat.     

Localization and mechanism of stimulatory feedback action of estrogen: effect of limbic forebrain implantation of estradiol benzoate on advancement of ovulation.

The sites and mechanism of the ovulation-inducing action of estradiol benzoate (EB) were studied by brain implantation of the crystalline steroid through chronically implanted outer cannula at 12:00 on diestrus day 2 in the 5-day cyclic rat. EB implantation in the medial amygdala or the bed nucleus of stria terminalis advanced cyclic changes in vaginal smears, timing of ovulatory LH release, and ovulation by 1 day, resulting in 4-day cycle. When implants in the bed nucleus of stria terminalis were placed for a shorter period of time on diestrus day 2, from 12:00 to 20:00, advancement of these parameters were similarly observed. Serum concentration of FSH and that of prolactin were significantly elevated at 20:00 on the same day in the rats implanted with EB in the medial amygdala or the bed nucleus of stria terminalis, compared with those in the non-treated controls. LH was not affected. The implantation in the arcuate nucleus was also effective to advance ovulation, but the anterior deafferentation prevented the effect. In contrast, EB implantation in the medial septal nucleus, the medial preoptic area, or the medial basal prechiasmatic area was consistently ineffective to advance vaginal cycle and ovulation. Multiunit activity in the arcuate nucleus showed an afternoon elevation on the day of implantation in these areas and as well on the day following, while it did not show such elevation on the day of implantation in the medial preoptic area. It is concluded that EB acts on the medial amygdala and the bed nucleus of stria terminalis in the mid-diestrus in 5-day cycle to stimulate FSH and prolactin release without affecting LH, which changes trigger a chain of reproductive events inducing early release of ovarian steroid responsible for early ovulatory gonadotropin release. The arcuate nucleus in one of the sites of stimulatory action of estrogen, but it requires the neural influence presumably from the medial amygdala and the bed nucleus of stria terminalis via the preoptic area for stimulating the ovulatory hormone release. EB exposure is considered to be endowed with the increase of its responsibility to this neural influence.     

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

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

Neonatal castration of male and female rats affects luteinizing hormone responses to estrogen during adulthood

We examined the positive and negative feedback effects of estradiol (E2) on luteinizing hormone (LH) and prolactin (Prl) secretion in adult male and female rats which were gonadectomized within 24 h after birth (long-term castrates) and compared these responses to those elicited by E2 in short-term castrated (7 days) adult males and females. The high serum E2 did not reduce the elevated serum LH concentrations in long-term castrates until 4 days of treatment. Also, only after negative feedback was established were the positive feedback actions of E2 observed. In contrast, Prl surges were observed after 2 days of E2, and baseline Prl serum levels were elevated by Day 3 of E2 in long-term castrated male and female rats. Some long-term castrates lacked both LH and Prl surges, and E2 was ineffective in altering basal gonadotropin secretion in these animals. Short-term castrated males had elevated serum Prl levels but no Prl surges. Seemingly, when the hypothalamus is deprived of estrogen or androgen from birth to adulthood, an equal percentage of males and females become refractory to the positive feedback effects of estrogen during adulthood. Thus, it is difficult to separate castration effects from those which may be produced by the endogenous androgen secreted during the first 26 h of life.     

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.     

An increase of pituitary 3', 5' cyclic adenosine monophosphate produced by estradiol benzoate in vitro: possible implication of this increase in the secretion of luteinizing hormone.

In an attempt to study the site and mechanism of action of estrogen in producing positive feedback control, porcine anterior pituitary slices were incubated in vitro in the presence of estradiol benzoate (EB). EB elevated pituitary cyclic AMP concentration within 5 min and augmented pituitary release of luteinizing hormone (LH). The magnitude of increase of cyclic AMP and LH release was related to the doses of EB used. Also, luteinizing hormone releasing hormone (LH-RH) elevated pituitary cyclic AMP concentration and stimulated pituitary release of LH. The magnitude of increase of cyclic AMP and LH release was inversely related to the doses of LH-RH used. EB and LH-RH were additive in increasing cyclic AMP. Progesterone and clomiphene citrate interfered with an increase of pituitary cyclic AMP produced by EB, but did not significantly affect the basal level of pituitary cyclic AMP. Testosterone propionate, human chorionic gonadotropin and hexestrol were without effect on either basal or stimulated level of pituitary cyclic AMP. Since cyclic AMP and dibutyryl cyclic AMP (DBC) stimulated LH release, it is suggested that EB directly stimulates the release of LH by augmenting cyclic AMP synthesis in the anterior pituitary.     

An acute increase in serum prolactin does not modify gonadotropin release in female rats

Attempts were made to find out whether hyperprolactinemia has an effect on the hypothalamo-pituitary response to estrogen feedback and LHRH stimulation. Adult female rats of Wistar strain were ovariectomized and received subcutaneous injection of 20 micrograms estradiol benzoate (EB) 3-4 weeks later (day-0). A second injection of 20 micrograms EB, when administered at noon on day-3, induced a highly significant increase in serum LH (p less than 0.001 vs. basal values), but not FSH, estimated at 1800 h on the same day. This EB-promoted LH release was not altered by pretreatment with rat PRL (5 micrograms/day), which was administered subcutaneously daily in the morning (1100 h) between day-1 and day-3. No statistical difference in the serum LH concentration was found when compared with the values for the control animals pretreated with 0.9% saline alone. Serum gonadotropins 15 min after LHRH administration (100 ng/100 g BW) in 32-day-old female rats were not statistically different between the animals pretreated with 5 micrograms PRL, which was given subcutaneously daily (at 0800 h) for 3 days, and the controls pretreated with 0.9% saline. These results suggest that an acute increase in serum PRL may not exert a negative effect on the gonadotropin release induced by estrogen feedback and LHRH stimulation.     

Action of estrogens on pituitary gonadotrophic function and follicular growth during diestrous in the rat (author's transl)

LH and FSH release during the afternoon of diestrus 1 on the one hand, and the rate of follicular growth on the morning of diestrus 1 or diestrus 2, on the other hand, were studied in 4-day cyclic female rats after injection of estradiol benzoate (10 microgram, s.c.) on the morning of estrus. LH and FSH release was observed between 15.00 and 19.00 h during diestrus 1, but did not occur after an injection of pentobarbital (30 mg/kg, i.p.) in diestrus 1 at 13.30 h. No luteinization resulted from an injection of estrogen. Slowed follicular growth was observed on the morning of either diestrus 1 or diestrus 2. These results suggest the existence of a "critical period" for LH and FSH release in diestrus 1 during the afternoon. They indicate that the ovarian response to the endogenous release of gonadotropins is dependent upon the state of development of the ovarian follicles.     

Integration of the effects of estradiol and progesterone in the modulation of gonadotropin secretion

Estradiol secreted by the maturing follicle is the primary trigger for the surge of gonadotropins leading to ovulation. Progesterone has stimulatory or inhibitory actions on this estrogen-induced gonadotropin surge depending upon the time and dose of administration. The administration of progesterone to immature ovariectomized rats primed with a low dose of estradiol induced a well-defined LH surge and prolonged FSH release, a pattern similar to the proestrus surge of gonadotropins. A physiological role of progesterone is indicated in the normal ovulatory process because a single injection of the progesterone antagonist RU 486 on the day of proestrus in the adult cycling rat and on the day of the gonadotropin surge in the pregnant mare's serum gonadotropin stimulated immature rat resulted in an attenuated gonadotropin surge and reduced the number of ova per ovulating rat. Progesterone administration brought about a rapid LHRH release and an decrease in nuclear accumulation of estrogen receptors in the anterior pituitary but not the hypothalamus. The progesterone effect was demonstrated in vitro in the uterus and anterior pituitary and appears to be confined to occupied estradiol nuclear receptors. In in vivo experiments the progesterone effect on estradiol nuclear receptors appeared to be of approximately 2-h duration, which coincided with the time period of progesterone nuclear receptor accumulation after a single injection of progesterone. During the period of progesterone effects on nuclear estrogen receptors, the ability of estrogens to induce progesterone receptors was impaired. Based on the above results, a model is proposed for the stimulatory and inhibitory effects of progesterone on gonadotropin secretion.     

Hormonal induction of incubation behavior in ovariectomized female turkeys (Meleagris gallopavo)

Two experiments were conducted to evaluate the effect of estradiol benzoate (EB), progesterone (P), ovine prolactin (oPrl), or their combinations on temporal patterns of serum luteinizing hormone (LH) and Prl and on nesting behavior in adult ovariectomized female turkeys. Levels of serum LH were initially reduced (p greater than 0.05) by the steroid treatments, while continuation of treatments induced surges of LH to levels comparable to pretreatment levels. Administration of steroid increased (p less than 0.05) levels of serum Prl, which persisted until termination of treatments. Administration of oPrl had no effect on levels of serum LH but blunted the steroid-induced release of Prl. Neither EB, P, nor oPrl treatments alone nor a combination of EB + P elicited nest occupation. Nest occupation was observed after administration of P only in turkeys pretreated with EB. Administration of oPrl maintained and advanced the P-induced nesting to persistent nesting behavior (incubation behavior). Once persistent nesting behavior was established, hormonal treatments were terminated, yet nesting behavior was maintained and serum samples showed increasing levels of Prl and decreasing levels of LH. It is suggested that incubation behavior in the female turkey is facilitated by the combined action of estradiol, P, and Prl.     

Hormonal regulation of progesterone secretion by cultured mouse granulosa cells

Secretion of progesterone by granulosa cells from preovulatory follicles of mice was determined during 2 weeks of cell culture in the presence of androgens, estrogen and pituitary gonadotropins. Androstenedione (10(-7) M) and dihydrotestosterone (10(-7) M) stimulated (P less than 0.05) progesterone secretion during the first 11 days of culture. In contrast, 17 beta-estradiol (10(-11)-10(-7) M) did not alter (P greater than 0.10) progesterone secretion throughout the culture period. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulated (P less than 0.01) the granulosa cells in a dose-dependent manner during the first few days of culture. This luteotropic effect was rapidly lost and at later times when FSH was not effective, LH suppressed (P less than 0.05) progesterone secretion. In the presence of prolactin (Prl) (1 microgram/ml), granulosa cells progressively secreted more progesterone during the first week of culture. After maximal stimulation on Days 7-9, progesterone secretion by Prl-treated cells began to decline, but the amount of steroid produced on Day 13 was still higher (P less than 0.05) than in control cultures. Androstenedione and Prl gave an additive effect on progesterone secretion during Days 3-5 of culture. Thereafter, the androgen, although stimulatory by itself, did not influence the luteotropic action of Prl. Unlike the early effect of androgens, 17 beta-estradiol acted synergistically with Prl to maintain maximal secretion of progesterone during the last 4 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma progesterone, estradiol, follicle-stimulating hormone and luteinizing hormone during diestrus and ovulation in rats with 5-day estrous cycles: effect of antibody against progesterone

Progesterone secretion remained significantly higher during diestrus in the 5-day cyclic rat than in the 4-day cyclic animal. Injection of a sufficient amount of antiprogesterone serum (APS) at 2300 h on metestrus in a 5-day cycle advances ovulation and completion of the cycle by 1 day in the majority of animals (75 and 80%, respectively). Progesterone (250 micrograms) administered with APS eliminated the effect of the antiserum. Within 2 h after administration of APS, levels of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) elevated significantly, while a significant elevation of plasma estradiol above the control value followed as late as 36 h after the treatment. None of the 5-day cyclic rats treated with APS showed ovulatory increases of FSH and LH at 1700 h on the second day of diestrus, although 3 of the 4 animals receiving the same treatment ovulated by 1100 h on the following day. The onset of ovulatory release of gonadotropins might have been delayed for several hours in these animals. These results indicate that recurrence of the 5-day cycle is due to an elevated progesterone secretion on the morning of diestrus, and suggest that a prolongation of luteal progesterone secretion in an estrous cycle suppresses gonadotropin secretion. Rather than directly blocking the estrogen triggering of ovulatory LH surge, the prolonged secretion of luteal progesterone may delay the estrogen secretion itself, which decreases the threshold of the neural and/or hypophyseal structures for ovulatory LH release.     

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

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

Effects of estradiol and progesterone on circulating LH and FSH secretion,and ovarian antral follicle growth in anestrous ewes

In the ewe, ovarian antral follicles emerge or grow in a wave-like pattern and each wave is preceded by a peak in the serum FSH level. The purpose of the current study was to investigate whether in anestrous Western White Face ewes, a combination of progesterone and estradiol affects the circulating FSH peak secretion and the number of small ovarian follicles. Five ewes were treated with subcutaneous silastic rubber implants (10 cm × 0.47 cm), containing 10% estradiol-17β w/w (controls) and 5 ewes were treated with the same estradiol implant, along with subcutaneous implants (11 cm × 0.48 cm) containing 10% progesterone w/w for 12 days. Daily transrectal ovarian ultrasonography and blood sampling was performed from 5 days before, to 9 days after the period of implantation. Blood samples were also taken every 12 min for a 6 h period on day −2, 6 and 13 prior to or after implant insertion (day 0, day of implant insertion). Pulsatility in the serum LH levels was eliminated by the implants (P < 0.05). During the implantation period, the serum FSH peak amplitude was lower in ewes treated with implants releasing estradiol and progesterone, compared to ewes treated with implants releasing only estradiol (P < 0.05). No follicular waves emerged during implant treatment in both groups (P < 0.05) and the number of serum FSH peaks did not differ during implantation, compared to before implantation. During the implantation period, the number of small follicles did not differ in ewes with implants releasing estradiol and progesterone, compared to ewes treated with implants releasing only estradiol. To conclude, supra-physiological concentrations of estradiol completely eliminated the serum LH pulsatality and suppressed the follicular wave emergence, while the FSH secretory peaks that preceded the follicular waves were not affected. Supra-physiological concentrations of estradiol-17β with physiological concentrations of progesterone decreased the serum FSH peak amplitude, eliminated the serum LH pulses, but did not decrease the size of the small follicle pool in anestrous ewes.     

Maturation of negative and positive estrogen feedback in the prepubertal female rat

The development of estrogen feedback system on gonadotropin release during sexual maturation in female rats was studied. Animals (Wistar strain rats) were divided into 6 groups according to their ages; 10, 15, 20, 25, 30, and 35 days. Both LH and FSH levels in serum increased significantly in response to ovariectomy in all age-groups studied when measured one week postoperatively, though in the rats aged 10-15 days the increase in FSH following castration was only slight. In rats older than 25 days, the postcastration gonadotropin rise, calculated as a percent increase from the basal figure, decreased gradually with increasing age. Ovariectomized rats injected with estradiol benzoate (EB, 5 micrograms/100 g BW) showed significantly lower levels of both LH and FSH than those in castrated controls. However, the inhibitory action of EB on postcastration gonadotropin output was found to be relatively less effective in rats older than 25 days. Ovariectomized rats primed with EB were again injected with a 2nd dose of EB (5 micrograms/100 g BW) at noon 3 days after priming. The 2nd EB injection induced a significant rise in LH 6 h later in 30- and 35-day-old, though not in younger, animals. On the other hand, the FSH response to EB was markedly enhanced during days 15-25 of age. These results indicate that the estrogen negative feedback action on gonadotropin release is already operating in female rats at a very early age, and that the brain sensitivity to estrogen decreases slightly during the late prepubertal phase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Follicle-stimulating hormone plays a role in the induction of ovarian follicular cysts in hypophysectomized rats.

Unabated stimulation by low doses of LH-like activity produces ovarian follicular cysts in both progesterone-synchronized immature rats and pregnant rats. Serum FSH is maintained in both of these models at values similar to those observed on diestrus. To determine whether unabated stimulation by basal serum FSH affects the ability of LH-like activity to induce cystic ovaries, immature hypophysectomized (HYPOXD) rats were given either no hormone (control); 2 micrograms ovine FSH (oFSH) once daily for 14 days beginning on Day 27; 0.5 IU hCG twice daily for 13 days beginning on Day 28 of age; or both oFSH and hCG (FSH + hCG) beginning on Day 27 and Day 28, respectively. By the end of the in vivo treatments (Day 40 of age), the largest follicles in the ovaries of control and hCG-treated HYPOXD rats were at the preantral stage of development, whereas the largest follicles present in ovaries from FSH-treated animals were atretic and at the small antral stage of development. In contrast, ovaries from rats treated with FSH + hCG displayed large follicular cysts by Day 37 of age. Of the serum steroids analyzed, only estradiol and androstenedione concentrations for animals treated with FSH + hCG were consistently elevated above values observed for control HYPOXD rats. Serum testosterone and dihydrotestosterone values were similar for hCG-treated and control HYPOXD rats throughout the in vivo treatments. In contrast, these steroids were elevated between Days 3 and 5 of FSH treatment (+/- hCG treatment). Serum progesterone and estrone values for all in vivo gonadotropin treatment groups were similar to those of controls. Serum insulin concentrations were not affected by any in vivo treatment. Incubates of follicles/cysts from FSH + hCG-treated HYPOXD rats contained more progesterone, androstenedione, and estradiol than incubates of follicles from any other in vivo treatment group. Follicles from all in vivo treatment groups responded to 8-bromo cAMP (cAMP) with increased in vitro progesterone accumulation. However, only follicles from FSH-treated and FSH + hCG-treated rats responded to cAMP with increased androstenedione and estradiol accumulation in vitro. Inclusion of 400 ng of either androstenedione or testosterone in the incubation medium enhanced progesterone accumulation in follicular incubates from control, hCG-treated, and FSH-treated HYPOXD rats, but did not enhance progesterone accumulation in follicular incubates from FSH + hCG-treated animals. Both androstenedione and estradiol production increased markedly under these conditions for follicles from all in vivo treatment groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of 17β-estradiol (estradiol) on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n=12), 150 (n=11) or 210 (n=12) days of age received estradiol benzoate (EB) osmotic pump implants 6/group and the remaining animals received vehicle control (C) implants except for 150-day C (n=5) on Day 0. On Day 10 blood samples were collected every 15 min for 8h and serum LH and estradiol concentrations were measured. Serum estradiol concentrations averaged 5 ± 1, 5 ± 1 and 7 ± 2 pg/ml for the 90-, 150- and 210-day-old gilts implanted with estradiol, respectively, whereas, serum estradiol concentrations was undetectable in C gilts. Mean serum LH concentrations, basal LH concentrations and serum LH pulse amplitude were less in EB-treated gilts at all ages compared to control animals. In contrast, LH pulse frequency initially was less in EB-treated gilts but subsequently increased (P<0.04) with age (from 0.8 ± 0.2 at 90 days to 5.2 ± 0.2/8h at 210 days), and at 210 days of age the pulse frequency was similar to C gilts. These results demonstrate an age related reduction in the sensitivity to the negative feedback action of estradiol on LH secretion and support the idea that the gilt conforms to the gonadostat hypothesis.     

Effect of estradiol benzoate and clomiphene on tyrosine hydroxylase activity and on luteinizing hormone and prolactin levels in ovariectomized rats

The effects of estradiol benzoate (EB) on tyrosine hydroxylase (TH) activity in the medial basal hypothalamus (MBH) and on plasma levels of luteinizing hormone (LH) and prolactin were studied in long-term ovariectomized rats. Administration of 10 μg EB produced significant elevation of TH activity on Days 1 and 3 following injection. LH levels were significantly lower than controls throughout the three day treatment period, although there was a significant increase from Day 1 to Day 2. TH activity and LH levels were inversely related throughout the experimental period. Clomiphene (15 μg/rat/day), a purported estrogen antagonist, was administered over a period of three days to control and EB-treated rats to determine whether the effect of EB on plasma LH levels was causally related to changes in TH activity. In rats receiving both EB and clomiphene, TH activity was lower and plasma LH was higher than after EB alone. The results support the hypothesis that the feedback effects of estradiol on LH release involve an action on the tuberoinfundibular dopaminergic (TIDA) neurons of the MBH and that clomiphene can oppose the inhibitory effect of estradiol on LH release by directly inhibiting TIDA neuron activity. Furthermore, EB-induced release of prolactin does not appear to involve detectable changes in the activity of TIDA neurons.     

Pituitary and ovarian hormone secretion and ovulation in gilts injected with gonadotropins during and after oral administration of progesterone agonist (Altrenogest)

We determined changes in plasma hormone concentrations in gilts after treatment with a progesterone agonist, Altrenogest (AT), and determined the effect of exogenous gonadotropins on ovulation and plasma hormone concentrations during AT treatment. Twenty-nine cyclic gilts were fed 20 mg of AT/(day X gilt) once daily for 15 days starting on Days 10 to 14 of their estrous cycle. The 16th day after starting AT was designated Day 1. In Experiment 1, the preovulatory luteinizing hormone (LH) surge occurred 5.6 days after cessation of AT feeding. Plasma follicle-stimulating hormone (FSH) increased simultaneously with the LH surge and then increased further to a maximum 2 to 3 days later. In Experiment 2, each of 23 gilts was assigned to one of the following treatment groups: 1) no additional AT or injections, n = 4; 2) no additional AT, 1200 IU of pregnant mare's serum gonadotropin (PMSG) on Day 1, n = 4); 3) AT continued through Day 10 and PMSG on Day 1, n = 5, 4) AT continued through Day 10, PMSG on Day 1, and 500 IU of human chorionic gonadotropin (hCG) on Day 5, n = 5; or 5) AT continued through Day 10 and no injections, n = 5. Gilts were bled once daily on Days 1-3 and 9-11, bled twice daily on Days 4-8, and killed on Day 11 to recover ovaries. Termination of AT feeding or injection of PMSG increased plasma estrogen and decreased plasma FSH between Day 1 and Day 4; plasma estrogen profiles did not differ significantly among groups after injection of PMSG (Groups 2-4). Feeding AT blocked estrus, the LH surge, and ovulation after injection of PMSG (Group 3); hCG on Day 5 following PMSG on Day 1 caused ovulation (Group 4). Although AT did not block the action of PMSG and hCG at the ovary, AT did block the mechanisms by which estrogen triggers the preovulatory LH surge and estrus.