Influences of retrochiasmatic surgical transection on mating and serum ovarian hormone levels in the androgenized rat

In previous studies female rats were shown to increase mating after retrochiasmatic surgical transections prior to ovariectomy and after ovariectomy with and without hormone replacement. This study was designed to determine if retrochiasmatic surgical transections (FC) or sham-FC would produce similar increased mating in androgenized rats. Four of thirty-one (13%) testosterone propionate (TP)-treated rats showed minimal mating without surgery, and 27 (87%) failed to mate. Mating occurred up to 30 days following FC, whereas temporary mating resulting from sham-FC had declined to presurgical levels by 30 days after surgery. Mating after ovariectomy was not facilitated by daily injections of 0.2μg of estradiol cypionate, but was facilitated after daily injections of 1.6 μg. TP-treated rats with FC showed more mating after 1.6 μg estradiol cypionate injections than the sham-FC and non-TP-treated controls. Serum estradiol-17β and progesterone levels at autopsy did not differ between TP-treated rats mating without surgery and those failing to mate. TP-treated rats with sham-FC surgery showed levels of estradiol-17β and progesterone similar to those of nonsurgical TP-treated rats and were combined into a single control group for comparison to the FC group. Serum levels of estradiol-17β did not differ between the control and FC group, whereas serum progesterone levels were decreased in the FC group. Serum levels of estradiol-17β and progesterone in TP-treated rats without FC were similar to baseline levels observed in this colony during the 4-day estrous cycle, but were less than peak levels observed at similar times on proestrus and diestrus Day 2, respectively. One possible effect of early androgen treatment would be to initiate a sustained inhibitory input to the mediobasal hypothalamus from the septal-preoptic area regions, thus causing deficits in mating. The lordosis responding in the androgenized rat after surgical interruption of the preoptic area-anterior hypothalamic continuum suggests that an inhibitory input was disrupted. It was further suggested that the higher mating observed in the FC group compared to the sham-FC group was not the result of higher ovarian hormone levels.     

Gonadotropin-releasing hormone (GnRH) inhibits ovulation induced with luteinizing hormone (LH) in proestrous hypophysectomized rats

In this paper we present evidence that a single low dose of the natural synthetic gonadotropin-releasing hormone (GnRH), inhibits ovulation induced by LH in proestrous-hypophysectomized rats. Rats hypophysectomized by the parapharyngeal route in the morning of proestrus received an intravenous injection of 100 or 300 ng GnRH at 1400 h immediately followed by 1.0 microgram LH per 100 g bw. In control groups, either one or both hormones were replaced with 0.9% NaCl. Ovulation was assessed the following morning by counting the ova present in oviductal flushings. All the rats treated with LH alone ovulated, and the addition of GnRH reduced significantly the number of ovulating rats and the number of ova per ovulating rat. In other groups of rats hypophysectomized in the morning of proestrus and treated in the same way, ovarian or adrenal secretory rates of estradiol and/or progesterone were measured after cannulation of the corresponding vein, in the afternoon of proestrus. In these animals, GnRH failed to inhibit either the ovarian progesterone surge observed 2 h after LH administration, or the adrenal progesterone secretion. All hypophysectomized rats showed lower ovarian secretory rate of estradiol than intact rats; this rate was not affected by treatment with LH or LH plus GnRH. The systemic estradiol levels in plasma of hypophysectomized rats were distributed within a range of 20 pg/ml to 50 pg/ml. The number of rats whose levels were above 21 pg/ml on estrus day was significantly higher in rats receiving 300 ng GnRH as compared to those receiving 100 ng GnRH, reaching values that surpassed the concentration found in intact, untreated animals at the same time of estrus. This effect did not depend on LH administration.     

Decreased luteinizing hormone-stimulated progesterone secretion by preovulatory follicles isolated from cyclic rats treated with the progesterone antagonist RU486.

Since administration of the antiprogesterone RU486 to cyclic female rats at metestrus and diestrus results in increased serum levels of LH, estradiol, and testosterone at proestrus, we investigated whether RU486 affects follicular steroidogenesis. Female rats with a 4-day estrous cycle, induced experimentally by a single injection of bromocriptine on the morning of estrus, were given RU486 (2 mg) twice daily (0900 and 1700 h) on metestrus and diestrus. At proestrus the preovulatory follicles were isolated and incubated for 4 h in the absence and presence of LH. In the absence of LH, accumulation of estradiol, testosterone, and progesterone in the medium was not different for RU486-treated rats and oil-treated controls. In contrast, LH-stimulated estradiol, testosterone, and progesterone secretions were significantly lower in RU486-treated rats compared with controls. Addition of pregnenolone to the incubation medium resulted in a significantly lower increase of progesterone in follicles from RU486-treated rats compared with those from oil-treated controls. This suggests that 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is decreased by administration of RU486 in vivo. Aromatase and 17 alpha-hydroxylase/C17-20 lyase activities were not affected: addition of substrate (androstenedione and progesterone respectively) did not affect differently the amount of product formed (estradiol and testosterone) in RU486- and oil-treated rats. However, LH-stimulated pregnenolone secretion was lower in follicles from RU486-treated rats compared with follicles from oil-treated controls, suggesting that either cholesterol side-chain cleavage activity or LH responsiveness is decreased. At proestrus the preovulatory follicles from RU486- and oil-treated rats were not morphologically different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estradiol induces and progesterone inhibits the preovulatory surges of luteinizing hormone and follicle-stimulating hormone in heifers

Objectives were to determine: 1) whether estradiol, given via implants in amounts to stimulate a proestrus increase, induces preovulatory-like luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges; and 2) whether progesterone, given via infusion in amounts to simulate concentrations found in blood during the luteal phase of the estrous cycle, inhibits gonadotropin surges. All heifers were in the luteal phase of an estrous cycle when ovariectomized. Replacement therapy with estradiol and progesterone was started immediately after ovariectomy to mimic luteal phase concentrations of these steroids. Average estradiol (pg/ml) and progesterone (ng/ml) resulting from this replacement were 2.5 and 6.2 respectively; these values were similar (P greater than 0.05) to those on the day before ovariectomy (2.3 and 7.2, respectively). Nevertheless, basal concentrations of LH and FSH increased from 0.7 and 43 ng/ml before ovariectomy to 2.6 and 96 ng/ml, respectively, 24 h after ovariectomy. This may indicate that other ovarian factors are required to maintain low baselines of LH and FSH. Beginning 24 h after ovariectomy, replacement of steroids were adjusted as follows: 1) progesterone infusion was terminated and 2 additional estradiol implants were given every 12 h for 36 h (n = 5); 2) progesterone infusion was maintained and 2 additional estradiol implants were given every 12 h for 36 h (n = 3); or 3) progesterone infusion was terminated and 2 additional empty implants were given every 12 h for 36 h (n = 6). When estradiol implants were given every 12 h for 36 h, estradiol levels increased in plasma to 5 to 7 pg/ml, which resembles the increase in estradiol that occurs at proestrus. After ending progesterone infusion, levels of progesterone in plasma decreased to less than 1 ng/ml by 8 h. Preovulatory-like LH and FSH surges were induced only when progesterone infusion was stopped and additional estradiol implants were given. These surges were synchronous, occurring 61.8 +/- 0.4 h (mean +/- SE) after ending infusion of progesterone. We conclude that estradiol, at concentrations which simulate those found during proestrus, induces preovulatory-like LH and FSH surges in heifers and that progesterone, at concentrations found during the luteal phase of the estrous cycle, inhibits estradiol-induced gonadotropin surges. Furthermore, ovarian factors other than estradiol and progesterone may be required to maintain basal concentrations of LH and FSH in heifers.     

The effect of estradiol and progesterone application on leptin concentration in ovariectomized rats

The aim of the present study was to investigate the effects of estradiol and progesterone application on leptin secretion in ovariectomised rats. The study included 30 adult female Sprague-Dawley rats. Rats were divided into three groups as follows: Group 1; Sham ovariectomy group (n=10), Group 2; Ovariectomy group (n=10), Group 3; Ovariectomized and estradiol propionate (450 microg/kg rat) and medroxyprogesterone acetate (15 mg/kg rat) supplemented group (n=10). One week after ovariectomy, rats in Group 3 were injected estradiol and progesterone for 4 weeks. Twenty-four hours after the last injection, rats were decapitated and blood samples were collected for leptin analysis. Serum leptin levels in Group 2 were found significantly higher than those in Groups 1 and 3 (p<0.01), while those in Group 3 were significantly lower when compared to Group 1 (p<0.0 1). The findings of the present study have shown that ovariectomy led to a significant increase in leptin levels. However, administration of estradiol and progesterone in combination following ovariectomy inhibites increases of leptin levels.     

Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol

Neuroprotective effects of estradiol are well characterized in animal experimental models. However, in humans, the outcome of estrogen treatment for cognitive function and neurological diseases is very controversial. Selective estrogen receptor modulators (SERMs) may represent an alternative to estrogen for the treatment or the prevention of neurodegenerative disorders. SERMs interact with the estrogen receptors and have tissue-specific effects distinct from those of estradiol, acting as estrogen agonists in some tissues and as antagonists in others. In this study we have assessed the effect of tamoxifen, raloxifene, lasofoxifene (CP-336,156), bazedoxifene (TSE-424), and 17beta-estradiol on the hippocampus of adult ovariectomized rats, after the administration of the excitotoxin kainic acid. Administration of kainic acid induced the expression of vimentin in reactive astroglia and a significant neuronal loss in the hilus. SERMs did not affect vimentin immunoreactivity in the hilus, while 17beta-estradiol significantly reduced the surface density of vimentin immunoreactive profiles. Estradiol, tamoxifen (0.4-2 mg/kg), raloxifene (0.4-2 mg/kg), and bazedoxifene (2 mg/kg) prevented neuronal loss in the hilus after the administration of kainic acid. Lasofoxifene (0.4-2 mg/kg) was not neuroprotective. These findings indicate that SERMs present different dose-dependent neuroprotective effects. Furthermore, the mechanisms of neuroprotection by SERMs and estradiol are not identical, because SERMs do not significantly affect reactive gliosis while neuroprotection by estradiol is associated with a strong down-regulation of reactive astroglia.     

Regulation of the immunoexpression of aquaporin 9 by ovarian hormones in the rat oviductal epithelium

The volume of oviductal fluid fluctuates during the estrous cycle, suggesting that water availability is under hormonal control. It has been postulated that sex-steroid hormones may regulate aquaporin (AQP) channels involved in water movement across cell membranes. Using a functional assay (oocytes of Xenopus laevis), we demonstrated that the rat oviductal epithelium contains mRNAs coding for water channels, and we identified by RT-PCR the mRNAs for AQP5, -8, and -9, but not for AQP2 and -3. The immunoreactivity for AQP5, -8, and -9 was localized only in epithelial cells of the oviduct. The distribution of AQP5 and -8 was mainly cytoplasmic, whereas we confirmed, by confocal microscopy, that AQP9 localized to the apical plasma membrane. Staining of AQP5, -8, and -9 was lost after ovariectomy, and only AQP9 immunoreactivity was restored after estradiol and/or progesterone treatments. The recovery of AQP9 reactivity after ovariectomy correlated with increased mRNA and protein levels after treatment with estradiol alone or progesterone administration after estradiol priming. Interestingly, progesterone administration after progesterone priming also induced AQP9 expression but without a change in mRNA levels. Levels of AQP9 varied along the estrous cycle with their highest levels during proestrus and estrus. These results indicate that steroid hormones regulate AQP9 expression at the mRNA and protein level and that other ovarian signals are involved in the expression of AQP5 and -8. Thus hormonal regulation of the type and quantity of water channels in this epithelium might control water transport in the oviductal lumen. water channels; epithelial cells; estradiol; progesterone     

Variations in the concentrations of androstenedione in peripheral plasma of women the day and during the menstrual cycle

The target tissues (e.g., hypothalamus, pituitary, uterus and vagina) of mature female ovariectomized rats show selective uptake of radioactivity in one hour after the injection of 6,7, ³H-estradiol-17β in a dose of 0.1 μg per 100 g body weight. Injection of 100 μg norethindrone or norgestrel per 100 g body weight 15 min before or 15 min after the administration of tritiated estradiol reduced the radioactivity in most target tissues, and also in the non-target tissues to a lesser extent. The uptake of radioactivity in the pituitary and uterus is reduced more by norethindrone than by norgestrel treatment when these Steroids were injected 15 min after estradiol-17β injection. It appears that there exists a competitive inhibition of estradiol-17β by these contraceptive Steroids in the rat. It is speculated that such competition with estradiol-17β may be an inherent property of the 17-substituted 19-nortestosterone group of Steroids.     

Effect of estrogens on phosphofructokinase activity of uterus, liver and kidney in rat and hamster

The effect of estradiol-17β on the phosphofructokinase (PFK) activity of uterus, liver and kidney in rat and hamster has been studied. 16 hours after a dose of 10 μg estradiol/100 g body weight, there are no differences in the uterotrophic responses of rats and hamsters and the increase in uterine PFK activity is similar in both animals. 48 hours after two doses of 100 μg estradiol/100 g body weight, the uterotrophic response is slightly higher in hamster than in rat, but rat uterus shows a greater increase of PFK activity than does hamster uterus.Hepatic and renal PFK activities in hamsters of both sexes are not modified 48 hours after two doses of 100 μg estradiol/100 g body weight. These results indicate that in hamster and rat, PFK is under estrogenic control in uterus and not in liver and kidney.     

Steroidal control of rat uterine 17β-hydroxysteroid dehydrogenase activity

The interconversion of estradiol-17β and estrone in the rat uterus is due to the action of 17β-hydroxysteroid dehydrogenase. Whole uteri or 800 × g supernatant fractions of the uteri were incubated in the presence of [³H] estradiol-17β and NAD at 37°C for 3 h or 1 h, respectively. In the mature rat uterus the oxidation of estradiol-17β and estrone was dependent on the stage of the estrous cycle, suggesting hormonal control. The 17β-hydroxysteroid dehydrogenase activity was highest at estrus (200 fmol estrone) and lowest at diestrus (80 fmol estrone). An enhancement of activity occurred when adult rats at each stage of the estrous cycle were administered estradiol-17β, while progesterone administration at each stage resulted in decreased enzyme activity. The uterine 17β-hydroxysteroid dehydrogenase activity of estradiol-17β treated ovariectomized rats was time and dose dependent but decreased when progesterone was administered with or without estradiol-17β administration. These results suggest that estradiol-17β caused an increase in enzyme activity that was inhibitable by progesterone in the rat uterus. The increased 17β -hydroxysteroid dehydrogenase activity may reflect a specific response of the rat uterus to estradiol-17β.     

Endocrine and antitumoral effects of R76713 in rats

Some effects of daily oral administration of a new non-steroidal aromatase inhibitor on the pituitary-gonadal and adrenal functions were investigated in female rats. At doses of 1 mg/kg twice daily or higher, R 76713 lowered plasma estradiol levels to the range measured after ovariectomy Plasma progesterone levels and uterine weights decreased whilst LH levels increased but to a lesser extent than after ovariectomy. The other hormonal data show that long-term administration of R 76 713 does not modify the gluco- and mineralocorticoid hormone levels even at the highest dose studied (20 mg/kg, 4 h after treatment). Furthermore, both ovariectomy and R 76 713 treatment (1 and 5 mg/kg twice a day) induced almost complete regression of 9,12-dimethyl-1,2-benzanthracene-induced mammary carcinoma in rats. The appearance of new tumors during the treatment period was completely inhibited by R 76 713 whilst multiplicity of the remaining tumors was dramatically reduced.     

Influence of Ovarian Hormones on Cortical Spreading Depression and Its Suppression by L-kynurenine in Rat

Migraine is sexually dimorphic and associated in 20–30% of patients with an aura most likely caused by cortical spreading depression (CSD). We have previously shown that systemic L-kynurenine (L-KYN), the precursor of kynurenic acid, suppresses CSD and that this effect depends on the stage of the estrous cycle in female rats. The objectives here are to determine the influence of ovarian hormones on KCl-induced CSD and its suppression after L-KYN by directly modulating estradiol or progesterone levels in ovariectomized rats. Adult female rats were ovariectomized and subcutaneously implanted with silastic capsules filled with progesterone or 17β-estradiol mixed with cholesterol, with cholesterol only or left empty. Two weeks after the ovariectomy/capsule implantation, the animals received an i.p. injection of L-KYN (300 mg/kg) or NaCl as control. Thirty minutes later CSDs were elicited by applying KCl over the occipital cortex and recorded by DC electrocorticogram for 1 hour. The results show that both estradiol and progesterone increase CSD frequency after ovariectomy. The suppressive effect of L-KYN on CSD frequency, previously reported in normal cycling females, is not found anymore after ovariectomy, but reappears after progesterone replacement therapy. Taken together, these results emphasize the complex role of sex hormones on cortical excitability. The CSD increase by estradiol and, more surprisingly, progesterone may explain why clinically migraine with aura appears or worsens during pregnancy or with combined hormonal treatments.     

Effect of ovarian hormones on glycosyltransferase activities in the endometrium of ovariectomized rats.

Some of the properties of galactosyl- and sialyltransferases present in rat endometrial tissue were investigated. The enzyme activities were found to be partly membrane-bound and partly in soluble form. The galactose enzyme was also present in uterine secretions. The specific activities of both galactosyl- and sialyltransferases were greatly enhanced in endometrium of ovariectomized rats following 17 β-estradiol injections, although the enzyme activities in the liver remained unaffected. Mixing experiments with the homogenates of endometrium from control and estradiol-treated rats failed to suggest the presence of any “activator” or “inhibitor” of the enzymes. Diethylstilbesterol, estrone, and estriol also stimulated galactosyl- and sialyltransferase activities, whereas testosterone stimulated sialyltransferase only. Prolactin administration had no effect on either of the enzymes. The effect of estradiol on both enzymes was shown to be dose-dependent and the specific activities of the enzymes started to increase about 6 hr after hormone administration, reaching a peak around 48 h. Progesterone, on its own, had no effect on the galactosyltransferase in ovariectomized rat endometrium but effectively prevented the stimulatory effect of estradiol. When estradiol-primed rats were treated with progesterone, it was found that very small doses of progesterone resulted in decrease of galactosyltransferase activity. In such animals sialyltransferase activity was stimulated by a low concentration of progesterone which was followed by inhibition at higher concentrations. These effects of ovarian hormones on glycosyltransferase activities in endometrium are compatible with earlier reports on the effects of these hormones on glycoprotein and glycosaminoglycan levels in rabbit uterus after ovariectomy (7). Regulation of glycosyltransferase activities in endometrium induced by estradiol and progesterone may bear some relationship to the “receptive” state of the uterus for blastocyst implantation.     

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.     

Effects of estradiol benzoate and progesterone on superoxide dismutase activity in the thymus of rats

The activity of mitochondrial superoxide dismutase (MnSOD) and cytosol superoxide dismutase (CuZnSOD) was measured in corresponding subcellular fractions prepared from the thymi of intact and chronically gonadectomized (GX) rats of both sexes, as well as of GX male and female rats injected subcutaneously with a single dose of 5 microg estradiol benzoate (EB) and/or 2 mg progesterone (P). Animals were sacrificed 2 h or 24 h following hormone treatment. In the females, the activity of MnSOD in the thymus was stable during the estrous cycle and did not change after ovariectomy. Treatment of GX females with estradiol benzoate resulted 2 h later in a significant elevation of MnSOD activity, whereas 24 h later the activity returned back to control values. On the other hand, treatment of GX females with progesterone had no effect on the MnSOD activity. However, combined hormone treatment, in which EB injection preceded progesterone injection by one hour, enhanced the effect on MnSOD activity similar to that of estradiol benzoate alone. The activity of CuZnSOD in cycling rats was increased in proestrus, whereas removal of the ovaries kept the values at low diestrus and estrus levels. Contrary to MnSOD, CuZnSOD activity did not change after EB treatment of GX females, while progesterone increased the enzyme activity at 2 h and 24 h after hormone treatment. However, combined EB+P treatment proved to be ineffective. In the males, neither MnSOD nor CuZnSOD activity was affected by the removal of testes or by progesterone treatment of GX animals. Only EB injection to GX rats significantly increased CuZnSOD activity 24 h later.     

Correlation of the changes of the frequency of perichromatin granules with the RNA content of the interchromatin region of uterine cells in normal and ovariectomized rats. A high resolution in situ hybridization and stereological study.

The changes in the number of perichromatin granules (PCG) and the alterations in the RNA content of the interchromatin and perichromatin regions caused by ovariectomy and estradiol injection were studied in rat endometrial fibroblast and myometrial muscle cells. Twelve rats were divided in four groups. A group of rats was fixed without any treatment, the other three groups were ovariectomized and processed 21 days after the operation. One of them was studied without further treatment, and two groups were injected intraperitoneally with 20 micrograms of 17 beta-estradiol hemisuccinate and fixed 0.5 and 2 h after the injection. The frequency of PCG was evaluated in preparations stained with EDTA procedure preferential for RNP. The alterations of RNA content were estimated by post-embedding high resolution in situ hybridization using a total DNA probe labeled with biotinilated nucleotides revealed by streptavidin coupled with 10 nm gold grains. Most of the non-nucleolar labeling is associated to RNP containing fibrils. Perichromatin and interchromatin granules are labeled to a lesser extent. Castration brings about a reduction of the number of PCG and of the numerical density of labeling in endometrial fibroblasts. The injection of estradiol causes a rapid increase in both parameters. On the contrary, the frequency of PCG and intensity of labeling of epithelial endometrial cells and in muscle cells increase after ovariectomy and are reduced by estradiol administration. These results suggest that estradiol may affect differentially various types of target cells in the same organ, and also that PCG are not the only nuclear compartment of pre-mRNA or mRNA altered by the changes in estradiol, the RNP containing fibrils located in the perichromatin and in the interchromatin regions are also involved.     

The phytoestrogen ferutinin improves sexual behavior in ovariectomized rats

The present study was designed to examine the effect of ferutinin chronic administration on sexual behavior of ovariectomized non-estrogen-primed rats. Starting from 3 weeks after ovariectomy, female rats were orally treated with ferutinin at the doses of 0.2 and 0.5 mg/kg, daily for 4 weeks. Ferutinin's effect was compared with that of estradiol benzoate, subcutaneously injected at the dose of 1.5 μg/rat twice a week. Animals were tested for sexual motivation, receptivity and proceptivity after 1, 2 and 3 weeks of treatment and for paced mating behavior after 4 weeks of treatment. Before each experimental test, they received progesterone injection (500 μg/rat).Both dosages of ferutinin significantly increased the receptive behavior in a time-dependent manner, as well as estradiol benzoate did. Also proceptive behaviors increased in ferutinin-treated animals in comparison with control ones. During the partner preference test ferutinin was able to induce a significant preference for a sexually active male over a sexually receptive female. Moreover, ferutinin restored a normal paced mating behavior, which had been suppressed by ovariectomy. These results show that ferutinin exerts an estrogenic activity in ovariectomized non-estrogen-primed female rats.     

Steroid-independent effect of gonadotropins on prostaglandin synthesis in rat Graafian follicles in vitro

The content of prostaglandins of the E-group (PGE) or F-group (PGF) was determined by radioimmunoassay in rat ovaries and in homogenates of cultured Graafian follicles. Intraperitoneal administration of luteinizing hormone (NIH-LH-S18; 10 μg/rat) at 9.00 h on any day of the estrous cycle caused an increase in ovarian PGE content within 5 h. The response was greatest on the day of proestrus (940% rise), i.e. when the ovary contains large follicles, and least at metestrus (80%). Follicles explanted from proestrous rats before the preovulatory gonadotropin surge responded to addition of LH (1–5 μg/ml) to the culture medium with a 10 to 30-fold increase in PGE and a 5-fold increase in PGF accumulation over a 5-h-period. Follicle stimulating hormone (NIH-FSH-S9; 10 μg/ml) caused a similar rise in follicular PGE accumulation, even after treatment of the FSH preparation with excess of an antiserum to the β-subunit of LH. Stimulation of follicular PG accumulation was unimpaired during suppression of progesterone and estrogen synthesis by aminoglutethimide. It is concluded that these steroids play no part in the mediation of the LH-effect on follicular prostaglandin formation.     

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.