INTRAOVARIAN ROLE OF STEROIDS IN GRANULOSA CELL FUNCTION

卵巢颗粒细胞的分化依赖于一种复杂的 经典内分泌控制以及神经调节 旁分泌和自分泌的影响。 越来越多的证据支持 优势卵泡的选择和分化 依赖于卵巢内对激素环境的控制， 颗粒细胞，特别是雌激素和雄激素在 这种自分泌调节。 拟议研究的目标是使用 颗粒细胞的原代培养物： 1.进一步了解雌激素的生理作用， 雄激素对促性腺激素刺激的LH受体的调节 并在啮齿动物模型中研究这种调制的机制 系统 2.检查几种临床上重要的直接性腺内效应 抗雌激素通过研究这些化合物对 促性腺激素刺激的培养细胞类固醇生成和受体诱导 大鼠颗粒细胞，并测试是否存在特定的，高 颗粒细胞中的亲和力抗雌激素结合位点。 3.将这些发现扩展到检查促性腺激素刺激的 人颗粒细胞中类固醇生成和LH受体诱导， 强调研究雌激素的自分泌作用和 催乳素作为显著的种属差异可能存在，并研究 抗雌激素对人颗粒细胞可能的直接性腺作用。 这些研究应加强我们对 通过类固醇控制卵巢内颗粒细胞分化，和 进一步了解临床上重要的 抗雌激素

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.