STEROID HORMONE METABOLISM

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This research proposal is concerned with factors which control or are related to ovarian steroid hormone metabolism and follicular growth and development. Three areas of interest will be explored: 1. 5 Alpha-Reductase activity. Work from our laboratory has implicated 5 Alpha-reduced androgen metabolism as a determinant in follicular growth and atresia. Human and hamster granulosa cells have significant 5 Alpha-reductase activity. Human cells from atretic follicles. DHT inhibits proliferation of rat granulosa cells. A specific inhibitor of 5 Alpha-reductase activity will be used to determine its effct on ovarian functions; specifically, follicular growth and development in vivo and granulosa cell proliferation and aromatase activity in vitro. 2. Angiogenic factor. We have preliminary evidence that follicular thecal cells produce an angiogenic factor in vitro. Angiogenesis is considered to be a crucial process in follicular growth. Our proposed studies will investigate the thecal angiogenic factor with respect to control of synthesis, characterization, relationship to luteal angiogenic factor, and follicular growth and atresia. 3. Subnstance P and Neurotensin. We have determined that SP and NT are found in the ovaries of at least 4 mammalian species. Hamster ovarian SP and NT vary in content during the cycle and are differentially disturbed within the ovary. In view of the recently discovered effects of GhRH in the ovary and testis, we propose to explore the significance of SP and NT in the reproductive system. Substance P and neurotensin content and distribution in the ovary and content in the anterior pituitary will be determined in various reproductive states of the rabbit and hamster, and in healthy and atretic human follicles. The possible effects of these two peptides in steroidogenesis and ollicular growth will be explored with both in vitro and in vivo studies. The proposed research will help us understand basic mechanisms involved in ovarian function, specifically atresia, blood vessel dynamics and neuroendocrine cotnrol of the ovary.