The steroidal modulation of FSH and LH secretion is an important area of study for a full understanding of the control of ovulation. The immature female rat castrated on Day 26 of age and primed with 0.1 Mug/kg BW of estradiol will be used to study the effects of 20 Alpha; 5 Alpha; 20 Alpha; 3 Alpha; 5 Alpha; 20 Alpha; and 3 Beta, 5 Alpha-reduced metabolites of progesterone on FSH and LH secretion. The selective release of FSH by 5 Alpha-dihydroprogesterone and selective release of LH by 3 Alpha-hydroxy-5 Alpha-pregnant-20-one will be confirmed in the 21-day-old rat injected with pregnant mare's serum gonadotropin. The requirement for 5 Alpha-reduction of progesterone for FSH release will be tested by using a 5 Alpha-reductase inhibitor. The effect of progesterone metabolites on hypothalamic LHRH secretion will be evaluated by measuring medial basal hypothalamic, preoptic area, and plasma LHRH levels along with serum LH and FSH levels at 15 min intervals after injecting the progestin in estrogen-primed castrated rats. The direct effect of progesterone and its metabolites on the pituitary will be determined by studying the effect of the steroids on cellular content and basal and LHRH stimulated release of LH and FSH in dispersed pituitary monolayer cell cultures. The separation of various gonadotroph populations will be attempted by using unit gravity and Percoll gradient techniques. The time course of progesterone effects on anterior pituitary nuclear estrogen receptors will be studied at 1, 2, 3, 4, 8 and 12 hrs after the progesterone injection in vivo and the effects of progesterone metabolites on estrogen receptor dynamics will be evaluated. The specificity of the effect of progesterone treatment of the nuclei or cytosol in depleting nuclear estradiol receptors in vitro will be studied by examining the effects of cholesterol, corticosterone and 5 Alpha-dihydrotestosterone. Whether transcription and/or protein synthesis is involved in the action of progesterone in the reduction of occupied nuclear estrogen receptors will be determined by using actinomycin-D and cycloheximide. Experiments will be done to determine the interactive effects of progesterone on estrogen receptors and estrogens on progesterone receptors and to determine if progesterone modulates its own receptors. In these studies, cytoplasmic and nuclear estradiol and progesterone receptors will be measured after treatment of castrated rats with various estrogen and progesterone regimens.
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