INTRAOVARIAN ROLE OF STEROIDS IN GRANULOSA CELL FUNCTION

卵巢颗粒细胞的分化依赖于复合体 经典的内分泌控制和神经调节的相互作用， 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的概念(S) 取决于卵巢内对荷尔蒙里程的控制 颗粒细胞，特别是雌激素和雄激素是关键 这项专制的规定。拟议研究的目标是使用 颗粒细胞的原代培养： 1.进一步了解雌激素和雌激素的生理作用 雄激素对促性腺激素刺激的黄体生成素受体的调节作用 啮齿动物模型中这种调节机制的形成和研究 系统。 2.检查几个临床重要因素对性腺的直接影响 通过研究这些化合物对雌激素的影响来抑制雌激素 促性腺激素刺激培养的类固醇激素合成和受体诱导 大鼠颗粒细胞，并检测其是否存在特异性、高 颗粒细胞中的亲和抗雌激素结合部位。 3.将这些发现扩展到促性腺激素刺激的检查 人颗粒细胞的类固醇激素合成和黄体生成素受体的诱导 重视研究雌激素的自分泌作用和雌激素的作用 由于催乳素可能存在显著的物种差异，因此要研究 抗雌激素对人颗粒细胞可能的直接性腺效应。 这些研究应加深我们对心力衰竭发病机制的认识。 类固醇对卵巢内颗粒细胞分化的调控作用 提供对临床上重要作用的进一步理解 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.