The differentiation of ovarian granulosa cells is dependent upon a complex interaction of classical endocrine control, as well as neuromodulatory, paracrine and autocrine influences. Increasing evidence supports the concept that the selection and differentiation of the dominant follicle(s) is dependent upon intraovarian control of the hormonal mileu seen by the granulosa cell, and specifically, that estrogens and androgens are key in this autocrine regulation. The goals of the proposed studies are to use primary cultures of granulosa cells to: 1. Further the understanding of the physiologic role of estrogens and androgens in the modulation of gonadotropin-stimulated LH receptor formation and study the mechanism of this modulation in the rodent model system. 2. Examine the direct intragonadal effects of several clinically important antiestrogens by studying the effects of these compounds on gonadotropin-stimulated steroidogenesis and receptor induction in cultured rat granulosa cells, and to test for the presence of specific, high affinity antiestrogen binding sites in granulosa cells. 3. Expand these findings to the examination of gonadotropin-stimulated steroidogenesis and LH receptor induction in human granulosa cells, emphasizing study of the autocrine role of estrogen and the role of prolactin as significant species differences may exist, and to study the possible direct gonadal effect of antiestrogens on human granulosa cells. These studies should enhance our understanding of the mechanism of the intraovarian control of granulosa cell differentiation by steroids, and provide further understanding of the actions of clinically important antiestrogens.
