The demonstrated activity of progestin to promote ovulation, coupled with the demonstration of progesterone receptor in the luteinizing, ovulating follicle and in the differentiated corpus luteum is compelling evidence for further investigation of the potential actions of progesterone in the ovulating follicle and corpus luteum. This proposal is directed to an investigation of the molecular and cellular events that are steroid/progesterone regulated during follicle rupture and luteinization of the periovulatory follicle, in the maintenance of luteal structure-function in the developed corpus luteum of the nonfertile cycle, and in the rescue of the corpus luteum during early pregnancy. Three treatment protocols will be used in which luteotropic support is sustained via exogenous luteinizing hormone/chorionic gonadotropin during the periovulatory interval, at midluteal phase of the cycle, and in simulated early pregnancy. These protocols are combined with progesterone ablation (using the 3B-hydroxysteroid dehydrogenase inhibitor, Trilostane) and progestin replacement (using the analog, R5020), followed by removal of periovulatory follicle or corpus luteum for analyses. These analyses include indices of tissue remodeling (protease expression, vascularization, cell proliferation), tissue differentiation (cholesterol utilization, steroid genesis, steroid receptor expression), and tissue regression (apoptosis). From these approaches, novel autocrine actions of progesterone in the luteinizing follicle and corpus luteum may be revealed.
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