Direct effect of estradiol on the number of dopaminergic receptors in the anterior pituitary, in ovariectomized rats

The effect of estradiol on anterior pituitary dopaminergic receptor content was studied in vivo and in vitro, in relation with the serum PRL secretion. A progressive and significant decrease in the number of these receptors was observed, a few hours before the serum release of PRL induced in ovariectomized females by a sequential treatment with different doses of estradiol benzoate. This decrease in the number of dopaminergic membrane receptors can be obtained as well in vitro, when anterior pituitaries, from ovariectomized rats, are incubated with 17 beta-estradiol. These results suggest that the stimulatory effect of estradiol on PRL secretion may be due, at least in part, to the direct "desensitization" to DA of anterior pituitary cells, which is produced by the decrease of dopaminergic receptor level.     

Neurokinin A in the anterior pituitary of female rats: effects of ovariectomy and estradiol.

The effect of acute and chronic ovariectomy and the substitutive treatment with 17-beta estradiol and/or progesterone on anterior pituitary levels of neurokinin A (NKA) was studied in female rats. Acute ovariectomy did not result in significant changes of NKA in the anterior pituitary gland as compared with the levels in diestrous intact rats, but a single injection of 5 micrograms of estradiol in ovariectomized rats significantly decreased NKA levels in the anterior pituitary gland. Progesterone was without effect and did not modify the decrease of NKA in the anterior pituitary gland induced by estradiol. In rats examined 11 to 17 days after ovariectomy, NKA in the anterior pituitary gland was significantly higher than in diestrous intact rats. In the hypothalamus, ovariectomy resulted in decreased levels of NKA in the median eminence-arcuate nucleus. Estradiol significantly reduced NKA stores in the anterior pituitary gland but increased them in the whole hypothalamus and in the median eminence-arcuate nucleus. Thus, estradiol seems to be a powerful regulator of NKA stores in the adenohypophysis and also in the hypothalamus.     

Effect of progesterone on tachykinin concentrations in the hypothalamus and anterior pituitary of female siberian hamsters.

The effect of progesterone on SP- and NKA-like immunoreactive substances in the hypothalamus and anterior pituitary was studied in ovariectomized and in ovariectomized, estrogen treated Siberian hamsters. Neither ovariectomy nor progesterone or estradiol treatment resulted in apparent changes in the tachykinin concentration in the hypothalamus. No effect of the treatments was seen on the release of tachykinins by hypothalami incubated in vitro in presence of high KCl concentrations. Ovariectomy resulted in a significant increase in the concentrations of both tachykinins in the anterior pituitary, as compared with intact animals. Progesterone (5 mg/animal) significantly reduced tachykinin concentrations in the anterior pituitary, as compared with the values found in ovariectomized animals. Estradiol completely suppressed the post-ovariectomy increase in anterior pituitary tachykinins, and progesterone did not significantly modify the response to estradiol. Lower doses of progesterone (250 microg or 1 mg/animal) significantly reduced NKA concentrations in the anterior pituitary of ovariectomized Siberian hamsters, but SP concentrations, although showing a similar tendency, were not significantly different in progesterone-treated as compared with ovariectomized, control animals. These results suggest that progesterone may modulate tachykinin stores in the anterior pituitary gland of Siberian hamsters.     

Effect of 5 alpha-dihydrotestosterone and dexamethasone on estrogen receptors of the anterior pituitary and uterus.

The administration of 5 alpha-dihydrotestosterone (5 alpha-DHT) and dexamethasone has been shown to attenuate estrogen-induced prolactin release in the estrogen-primed rat. Therefore, the effect of these compounds was studied on anterior pituitary and uterine estrogen receptors. Injection of 0.8 mg/kg body weight of 5 alpha-DHT to ovariectomized adult rats treated with 2 micrograms estradiol/d for 4 days resulted in a significant decrease in occupied nuclear estrogen receptors of the anterior pituitary but not the uterus. Estrogen priming was essential for 5 alpha-DHT effect on occupied nuclear anterior pituitary estrogen receptors because this effect did not occur in ovariectomized vehicle-treated control animals. The administration of 1 mg/kg body weight of dexamethasone brought about a decrease in uterine but not anterior pituitary nuclear estradiol receptors. These results provide further evidence that the regulation of estrogen receptor dynamics is different in the anterior pituitary and the uterus and that different steroids can exert tissue-specific effects.     

Antagonism of estrogen-induced prolactin release by progesterone

Previous work from our laboratory has shown that during the process of nuclear occupancy of the progesterone receptor complex (1-2 h), nuclear estradiol receptors of the anterior pituitary are depleted. The purpose of this study was to determine whether the depletion of nuclear estradiol receptors by progesterone had functional biological significance. The ovariectomized (26 days of age) immature rat was used as the model for analysis of this question. The ability of estradiol to release prolactin from the anterior pituitary was the function chosen to determine the biological significance of the progesterone and estradiol interactions. In response to estradiol exposure (2 micrograms/rat), prolactin release reached peak values from 8 h to 12 h and returned to control levels by 24 h. A second injection of estradiol 13 h after the initial injection stimulated a second increase in serum prolactin at 25 h. This model of two injections of estradiol 13 h apart served to provide adequate levels of anterior pituitary progesterone receptors and elevated serum prolactin levels upon which superimposed progestin modulation could be examined. A single injection of progesterone (0.8 mg/kg BW) 1 h before the second estradiol injection blocked the increase in serum prolactin. This action was a receptor-mediated event because progesterone had no effect without estrogen priming or when the progesterone antagonist RU486 was used. Finally, when the interval between the progesterone and second estradiol injection was extended to 4 h, a time period when progesterone does not deplete pituitary nuclear estrogen receptors, the estrogen-induced increase in serum prolactin was not blocked.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of galanin secretion from pituitary cells in vitro by estradiol and GHRH

The effects of estradiol and growth hormone-releasing hormone (GHRH) on galanin release from anterior pituitary cells were examined in vitro. 17-β-Estradiol (0.001–10 nM) increased galanin secretion from anterior pituitary cells in a concentration-dependent manner. Estradiol (10 nM) increased galanin release 300 and 600% from pituitary cells of ovariectomized and male rats, respectively. Immunocytochemical studies demonstrated that estradiol (10 nM) increased the number of galanin-containing cells twofold after 4 days in culture. Growth hormone-releasing hormone (1 and 10 nM) increased and SRIF (1 and 10 nM) decreased galanin release from pituitary cells of ovariectomized and male rats. We conclude that estradiol increases galanin release by a direct effect on pituitary cells, in part by increasing the number of pituitary cells synthesizing galanin. In addition, GHRH stimulates galanin release when estradiol levels are low.     

Estrogens sensitize anterior pituitary gland to apoptosis

Tissue homeostasis results from a balance between cell proliferation and cell death by apoptosis. Estradiol affects proliferation as well as apoptosis in hormone-dependent tissues. In the present study, we investigated the apoptotic response of the anterior pituitary gland to lipopolysaccharide (LPS) in cycling female rats, and the influence of estradiol in this response in ovariectomized (OVX) rats. The OVX rats were chronically estrogenized with implanted Silastic capsules containing 1 mg of 17beta-estradiol (E2). Cycling or OVX and E2-treated rats were injected with LPS (250 microg/rat ip). Apoptosis was determined by the terminal deoxynucleotidyl-mediated dUTP nick-end labeling (TUNEL) method in sections of the anterior pituitary gland and spleen. Chronic estrogenization induced apoptosis in the anterior pituitary gland. Acute endotoxemia triggered apoptosis of cells in the anterior pituitary gland of E2-treated rats but not of OVX rats. No differences were observed in the apoptotic response to LPS in spleen between OVX and E2-treated rats. The apoptotic response of the anterior pituitary to LPS was variable along the estrous cycle, being higher at proestrus than at estrus or diestrus I. Approximately 75% of the apoptotic cells were identified as lactotropes by immunofluorescence. In conclusion, our results indicate that estradiol induces apoptosis and enables the proapoptotic action of LPS in the anterior pituitary gland. Also, our study suggests that estrogens may be involved in anterior pituitary cell renewal during the estrous cycle, sensitizing lactotropes to proapoptotic stimuli.     

Reserpine induced changes in the estradiol uptake by the pituitary and the uterus in ovariectomized rats.

Reserpine treatment produced a marked decrease of the in vitro binding of estradiol to the nuclear fraction of the uterus. A similar observation was made when reserpine was given into the incubation medium of uterine tissue. In contrast to these findings both in vitro and in vivo reserpine administration resulted in an increase of the estradiol binding to the nuclear fraction of the anterior pituitary in ovariectomized rats. The binding capacity of cytosol fraction after reserpine administration did not show significant alterations. In addition to these observations it is worth to mention that reserpine treatment resulted in a significant decrease of the estradiol-induced increase of uterus weight in ovariectomized rats.     

Pregnenolone sulfate modulates angiotensin II-induced inositol 1,4,5-trisphosphate changes in the anterior pituitary of female rat

The present study was designed to test whether pregnenolone sulfate can influence the angiotensin II (AngII) action in the anterior pituitary. Female rats were ovariectomized and 10 days after operation were treated with either 50 or 250 microg per animal in one of the following substances: oil (control), pregnenolone sulfate (PREG-S), estradiol benzoate (E(2),) progesterone (P), or dehydroepiandrosterone sulfate (DHEA-S), given in single intraperitoneal injection. Because AngII is known to act in the anterior pituitary through the phosphatidiloinositol breakdown, thus increasing the level of inositol-1,4,5-trisphosphate (IP(3)), the IP(3) concentration was determined 24 h after the injection in the anterior pituitary homogenate after in vitro exposure to AngII. Among the tested steroids only PREG-S enhanced the basal (without AngII) and AngII-induced level of IP(3) in both doses used. There was no difference between the effect of a high and low dose of PREG-S. These results show that PREG-S may modulate AngII action in the anterior pituitary, regardless of the presence of ovary.     

Effect of melengestrol acetate on the organ weight & the mammary lobulo-alveolar development in rats

The effect of melengestrol acetate (MGA) on the organ weight and the mammary lobulo-alveolar development in rats was studied. 33 adult female rats were divided into 4 groups: 1) 5 mcg MGA/gm feed; 2) a normal diet; 3) ovariectomized and fed 5 mcg MGA/gm feed; and 4) ovairectomized and fed a normal diet for 30 days when the rats were sacrificed. In the second experiment, 21 primiparous female rats were ovariectomized, and 10 days later 1 group was injected with 2 mcg estradiol for 10 days, while the 2nd group was injected with 50 mcg MGA/day, and the 3rd group with estradiol plus MGA in the above doses. The animals were sacrificed after 10 days of treatment. MGA decreased anterior pituitary, ovary, uterus, and adrenal weight, but enhanced (p less than .01) mammary lobulo-alveolar development in intact rats. No effect on mammary development in ovariectomized rats was noticed whether the drug was given orally or by injection; however uterine and adrenal weights were reduced. MGA plus estradiol caused significant (p less than .01) mammary growth in ovariectomized rats as compared with that in rats given MGA or estradiol alone. Uterine weight was increased slightly after supplementation with estradiol, but adrenal weight did not show improvement. It is suggested that MGA is without any estrogenic activity and therefore requires the presence of ovaries or estrogen to exhibit development of mammary growth.     

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.     

Role of 17 beta-hydroxysteroid dehydrogenase in the modulation of nuclear estradiol receptor binding by progesterone in the rat anterior pituitary gland and the uterus

Progesterone has been shown to decrease occupied pituitary and uterine nuclear estradiol receptor (E2R) binding in mature and immature estrogen-primed rats. Progesterone has also been shown to stimulate pituitary but not uterine 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in the rat. The conversion of estradiol to its less active metabolite estrone by 17 beta-HSD and activation of phosphatase are among mechanisms considered to be involved in the reduction of E2R. To determine if 17 beta-HSD stimulation was a mechanism by which progesterone induced nuclear E2R decrease, the synthetic estrogen ethinylestradiol, which is not oxidized by 17 beta-HSD, was used instead of estradiol to prime adult ovariectomized rats. When ethinylestradiol-primed rats received 0.8, 2.0 or 4.0 mg/kg body wt of progesterone 2 h before sacrifice, the total and occupied nuclear E2R accumulation in the anterior pituitary by a subsequent ethinylestradiol injection 1 h later did not show any decrease. This response was different from that observed previously in estradiol-primed animals in which progesterone showed a multiphasic decrease of occupied form of nuclear E2R. However, in the uterus of ethinylestradiol-primed rats, a partial decrease of total and occupied nuclear E2R accumulation was observed in the presence of the three doses of progesterone used. The decrease of uterine nuclear E2R with the three progesterone doses was different from the dose-dependent effect of progesterone observed in the uterus of estradiol-primed rats. Affinity constants of the interaction between [3H]estradiol and the nuclear E2R were similar among groups treated with ethinylestradiol, estradiol and progesterone. These results demonstrate the involvement of 17 beta-HSD in the reduction of anterior pituitary gland E2R by progesterone in the estradiol-treated animals. Furthermore, the mechanism of decrease of E2R by progesterone in the uterus appears to be different from the pituitary gland.     

Discrete early changes in cellular subpopulations of rat uterine and anterior pituitary estrogen receptors in response to acute exposure to exogenous estradiol

Distribution of estrogen receptors among ligand-occupied and unoccupied species in cytosolic and nuclear subcellular compartments has been analyzed as an acute response to administration of 5 micrograms of estradiol in adult female rats. Patterns of anterior pituitary and uterine receptor turnover were monitored at intervals over a 5-h period, using either intact or 2-weeks ovariectomized animals. In terms of total cellular receptor content, initial levels were higher in castrate animals, but rapidly fell to intact levels within an hour following estradiol injection. Cycloheximide given shortly before estradiol had no effect on total pituitary receptor patterns, but appeared to result in an elevation in total uterine receptor content at early intervals. Unoccupied cytosol receptors were rapidly depleted and, with the exception of castrate pituitary samples, showed some replenishment within 5 h, all of which was cycloheximide-sensitive. Initially, occupied cytosol receptors were low in intact rats, but were present at levels approaching those of the unoccupied cytosol receptor forms in the ovariectomized rat tissues. Occupied cytosol receptor levels fluctuated in response to estradiol. Subpopulations of nuclear receptors, especially the unoccupied species, showed significant tissue specificity. In the uterus, unoccupied nuclear forms were initially present in high amounts, and the levels did not change in response to estradiol administration. In the pituitary, the levels of these receptors rose and subsequently fell over the 5-h interval. Cycloheximide conferred a similar biphasic response to estradiol upon the otherwise insensitive unoccupied nuclear forms of the uterus. Occupied nuclear receptors turned over completely during the 5-h study interval, with the kinetics being faster in the castrate than the intact tissues. Cycloheximide affected occupied nuclear forms of the uterus only, dramatically increasing their levels in response to estrogen and causing prolonged retention in the castrate animal model. Collectively, the cycloheximide effects on this system are consistent with early estrogen induction or stimulation of a protein which inhibits accumulation of occupied or unoccupied receptor species within the nucleus. This re-examination of all forms of cellular estrogen receptors as they fluctuate acutely in response to exogenous estrogen has revealed several heretofore undetected responses which must be incorporated into the overall scheme of early estrogen action.     

Temporal response of uterine prostaglandins to estradiol treatment in the ovariectomized-pregnant rat

Previous studies in our laboratory have shown that 24 hours of estradiol treatment significantly enhanced uterine prostaglandin (PG)F, PGE and thromboxane B2 (TxB2) levels but had no effect on 6-Keto-PGF1 alpha (6KF) concentrations in ovariectomized-pregnant rats. One explanation for the lack of an augmentation in 6KF was a temporal difference in response (i.e. 6KF increased and decreased within the 24 hour period). To test this possibility rats were ovariectomized on day 19 of pregnancy and sacrificed 0, 4, 8, 12, 16, 20 and 24 hours after estradiol treatment. Uterine tissue and venous plasma were analyzed for PGs by radioimmunoassay. No significant (p greater than .05) alterations were detected for any of the uterine PGs at 0, 4, 8 and 12 hours. However, at 16 hours PGF, TxB2 and PGE all showed significant (p less than .05) increases (2.4, 3.4 and 2.1 fold, respectively) compared to 12 hours. In contrast, no significant augmentation in 6KF levels (p greater than .05, 1.3 fold) was detected at 16 compared to 12 hours although it was enhanced relative to 0 and 4 hours. In addition, PGF, TxB2 and PGE, but not 6KF, showed further increases 24 hours after estradiol administration. No alterations were found (p greater than .05) for any of the PGs in uterine venous plasma at the time points studied. In summary, uterine PGF, PGE and TxB2 net production appears to be more enhanced by estradiol treatment than 6KF at the time points studied. In addition, there is a slight, but significant, difference in the temporal response characteristics of 6KF compared to the other PGs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prolactin and estradiol on rat striatal dopamine receptors

Chronic estrogen treatment has been found to increase the level of rat striatal dopamine receptors. Since it is well known that estrogen treatment increases circulating prolactin levels, we have investigated the possibility that the stimulatory effect of estrogens on dopamine receptors is exerted via prolactin. Ovariectomized female or intact male rats were implanted with three adenohypophyses under the kidney capsule or treated with 17 β-estradiol (10 μg, twice daily) for 2 weeks. In animals of both sexes, the pituitary-implanted and estradiol-treated rats showed higher levels of [³H]spiperone binding to striatal dopamine receptors. This effect of estradiol or pituitary implants on dopamine receptors was further investigated in ovariectomized rats. The pituitary-implanted and estradiol-treated rats had elevated plasma prolactin levels and an increased density of striatal dopamine receptors without alteration of their affinity. The role of the pituitary in the effect of estradiol was next investigated using hypophysectomized female rats treated with 17 β-estradiol (10 μg, twice daily), o-prolactin (500 μg, twice daily) or bearing three anterior pituitary implants. The implants as well as the treatment with estradiol or prolactin increased the level of striatal dopamine receptors in hypophysectomized rats while, as expected, the estradiol-treated animals did not have elevated plasma prolactin levels. The present data indicate that high prolactin levels lead, as observed with chronic estradiol treatment, to an increased density of striatal dopamine receptors. However, the effect of estradiol may not be explained exclusively by increased prolactin levels since a similar stimulatory effect is observed in hypophysectomized animals.     

Hypothalamic corticotropin-releasing factor immunoreactivity is reduced during induction of pituitary tumors by chronic estrogen treatment

The role that estrogen plays in the regulation of corticotropin-releasing factor (CRF) is not known. A radioimmunoassay specific for rat CRF was utilized to measure the CRF-like immunoreactivity (CRF-ir) in the hypothalamus of ovariectomized rats treated with estradiol for periods up to 12 weeks. Compared to ovariectomized controls, estradiol treatment resulted in significantly reduced CRF-ir after 3 and 12 weeks, although no significant change was seen after 8 weeks. Anterior pituitary (AP) weight was greatly increased by estradiol treatment at all time points studied. Bromocriptine treatment for the last 3 weeks of the 12-week period, or removal of estradiol for 3 weeks after 9 weeks of treatment did not reverse the changes in CRF-ir even though significant regression of tumor size was achieved. There was no correlation between AP weight and CRF-ir in individual animals. These data show that chronic treatment with estrogen reduced hypothalamic CRF-ir content. Neither a direct estrogenic effect or an indirect effect mediated through alterations in the adenohypophysis could be ruled out.     

Pituitary uptake of 125I-D-Leu6, Des-Gly N2(10) LH-RH-ethylamide in ovariectomized rats pretreated with oestradiol-17 beta.

The objective of this study was to determine if pretreatment of ovariectomized rats with oestradiol-17 beta affects the anterior pituitary uptake of 125I-D-Leu6, Des-Gly NH2(10)-LH-RH-ethylamide (125I-D-Leu6-LH-RH). Oestradiol-17 beta (0.5 microgram/0.5 ml oil) or oil was administered to ovariectomized rats at 2, 4, 8, 12, 16, 20 or 24 h before death, and at 30 min before death, 5 ng 125I-D-Leu6-LH-RH were injected intravenously. The serum LH response to analogue administration in oil-treated rats did not change over time, but that in oestradiol-treated rats was depressed for 4 h and restored 8-24 h after oestradiol treatment, with the greatest response being at 16 h. However, the pituitary (adrenal, CNS cortex and thyroid) uptake of 125I-D-Leu6-LH-RH in oestradiol-treated and control rats did not change over the 24-h time period. These data suggest that oestradiol-17 beta does not affect pituitary responsiveness to 125I-D-Leu6-LH-RH by inhibiting or facilitating the uptake of this analogue by the anterior pituitary.     

Uterine cyclic AMP formation: biphasic effect of estrogen on catecholamine sensitivity.

Female, ovariectomized rats were treated with estradiol and then, after various time periods, given an intravenous injection of isoproterenol or epinephrine. 30 seconds later uteri were frozen $\text{in}$$\text{situ}$ and assayed for cyclic AMP and glycogen phosphorylase. The cyclic AMP response to catecholamines was significantly depressed as early as 30 minutes after estrogen and at 6, 12 and 24 hours was 50% of that in non-estrogen-treated controls. Catecholamine-induced glycogen phosphorylase activation was unchanged until 24 hours after estrogen when it was significantly increased over controls. At 48 hours of estrogen both the cyclic AMP and phosphorylase responses to catecholamines were greater than controls. Estrogen regulates uterine β-adrenergic sensitivity but the time courses of estrogen effects on the cyclic AMP and glycogen phosphorylase response changes are different. Catecholamine-induced uterine cyclic AMP formation is biphasic: suppression during the first 24 hours of estrogen followed by recovery and finally augmentation by 48 hours. Catecholamine-induced glycogen phosphorylase activation shows only augmentation after 24–48 hours of estrogen. It is concluded that estrogen has independent effects on the β-adrenergic-glycogen phosphorylase activation pathway at two different points; one prior to cyclic AMP formation and another after cyclic AMP formation.     

Inhibitory effects of the antiprogestin, RU 486, on progesterone actions and luteinizing hormone secretion in pituitary gonadotrophs

The effects of RU 486 on the modulation of LH release by progesterone were investigated in cultured anterior pituitary cells from ovariectomized adult female rats. The inhibitory effect of progesterone on LH secretion was demonstrable in estrogen-treated pituitary cells, in which addition of 10(-6) M progesterone to cells cultured in the presence of 10(-9) M estradiol for 52 h reduced the LH response to GnRH (10(-11) to 10(-7) M). When RU 486 was superimposed upon such combined treatment with estradiol and progesterone, the suppressive effect of progesterone on GnRH-induced LH release was completely abolished. The converse (facilitatory) effect of progesterone on LH secretion was observed in pituitary cells pretreated with 10(-9) M estradiol for 48 h and then with 10(-6) M progesterone for 4 h. When RU 486 was added together with progesterone during the 4 h treatment period, the facilitatory effect of progesterone was blocked and LH release fell to below the corresponding control value. The direct effect of RU 486 on LH secretion in the absence of exogenous progesterone was evaluated in cells cultured in the absence or presence of 10(-9) M estradiol and then treated for 4 to 24 h with increasing concentrations of RU 486 (10(-12) to 10(-5) M) and stimulated with GnRH (10(-9) M) during the last 3 h of incubation. In estrogen-deficient cultures, 4 h exposure to RU 486 concentrations of 10(-6) M and above decreased the LH response to GnRH by up to 50%. In cultures pretreated with 10(-9) M estradiol, GnRH-stimulated LH responses was inhibited by much lower RU 486 concentrations, of 10(-9) M and above. After 24 h of incubation the effects of RU 486 were similar in control and estradiol-pretreated pituitary cell cultures. Thus, RU 486 alone has a significant inhibitory effect on LH secretion that is enhanced in the presence of estrogen. The antiprogestin is also a potent antagonist of both the inhibitory and the facilitatory actions of progesterone upon pituitary gonadotropin release in vitro.     

Effects of neonatal administration of monosodium glutamate and castration on neurokinin A levels in the hypothalamus and anterior pituitary of rats.

The effects of neonatal administration of monosodium glutamate (MSG) and castration on hypothalamic and anterior pituitary levels of neurokinin A (NKA) were studied in male and female rats killed at 46 days of age. In male rats treated neonatally with MSG, body, anterior pituitary, testis, ventral prostate, and seminal vesicle weights and serum testosterone levels were significantly lower than in saline-injected controls. Hypothalamic NKA was significantly lower in MSG-treated male rats as compared with the controls, and no apparent changes were recorded in anterior pituitary NKA. Orchidectomy was followed by a significant decrease in hypothalamic NKA in saline controls, but not in MSG-treated rats. In female rats treated with MSG, there was a significant decrease in body, anterior pituitary, and ovarian weights, as compared with saline-injected controls, but no significant differences were observed in uterine weights and serum estradiol levels. Hypothalamic NKA was lower, although not significantly, in MSG-treated rats as compared with the respective controls, and no differences were recorded in anterior pituitary NKA levels. Ovariectomy was followed by a significant decrease in hypothalamic NKA in both MSG-treated and control rats, but NKA in the anterior pituitary was significantly increased after ovariectomy only in saline-treated controls, whereas MSG-treated females failed to show this response. It is concluded that neonatal MSG treatment resulted in a decrease of hypothalamic NKA, which was particularly pronounced in male rats without any significant change in anterior pituitary NKA levels. The response of hypothalamic NKA to castration and the response of anterior pituitary NKA to ovariectomy were also altered in MSG-treated rats; this may reflect a functional block of some neuroendocrine functions of the hypothalamus that resulted from the neuronal lesions induced by MSG.