ACTIONS OF ESTROGEN IN MATURING GRAAFIAN FOLLICLES

这项工作的总体目标是更好地理解 卵巢中的激素作用，特别关注雌激素的特异性 调节颗粒细胞胆固醇代谢。 研究中 该R 01赠款的前3年为以下方面提供了良好的基础： 继续强调雌激素的控制以下关键步骤， 调节卵巢细胞中的固醇利用： 1)从乙酰辅酶A从头生物合成胆固醇， 2)细胞胆固醇酯储存的周转， 3)脂蛋白的结合、内化和降解， 携带胆固醇， 4)胆固醇向细胞色素的传递及其利用 含P-450的胆固醇侧链裂解反应。 在第一个任期内发展的具体背景， 也将允许更严格的评价雌激素的作用， 卵巢中激素作用的生物放大器。 我们尤其 最近证明雌二醇与 某些有效的卵巢效应激素（如FSH和纯生长调节素 C）。 雌激素协同增强乳腺癌细胞增殖的机制 颗粒细胞中孕酮的生物合成能力将在 与细胞固醇代谢中每个主要步骤的关系 由我们的具体目标（1）至（4）定义。 这些新的研究将 部分利用我们刚刚开发的某些脂质研究方法， 应用于研究雌激素单独的作用，他们也将 采用新的和更精确的技术来阐明 颗粒细胞对胆固醇的处理。 开发这些的时间 最近（1985年1月）在RCDA下提供了额外的技术 支持. 因此，我们预计， 关于雌二醇调节作用的性质和 雌二醇生物放大激素的机制 在卵巢中的作用。 这些知识将有助于澄清重大的 使颗粒细胞为高发病率做好准备的内分泌机制 孕酮生物合成最终需要正常的类固醇生成 黄体的功能 因此，这些调查是 可能有助于在非洲大陆采取新的生育率调节办法， 人类、家畜或濒危野生物种。

The overall objective of this work is a more refined understanding of hormone action in the ovary, with a particular focus on estrogen's specific regulation of cholesterol metabolism in granulosa cells. Studies during the first 3 years of this R01 grant have provided an excellent basis for a continuing emphasis on estrogen's control of the following key steps that regulate sterol utilization in ovarian cells: 1) De novo biosynthesis of cholesterol from acetyl coenzyme A, 2) The turnover of cellular cholesteryl ester stores, 3) The binding, internalization and degradation of lipoproteins, which carry cholesterol, and 4) The delivery of cholesterol to, and its utilization in, the cytochrome P-450 containing cholesterol side-chain cleavage reaction. The specific background developed during the first tenure of this grant will also permit a more exacting appraisal of the role of estrogen as a biological amplifier of hormone action in the ovary. In particular, we have recently demonstrated that estradiol interacts synergistically with certain potent ovarian effector hormones (e.g. FSH and pure somatomedin C). The mechanism(s) subserving estrogen's synergistic enhancement of progesterone biosynthetic capacity in granulosa cells will be examined in relation to each of the principal steps in cellular sterol metabolism defined by our specific aims (1) through (4). These new studies will utilize in part certain lipid research methods we have just developed and applied to investigating the actions of estrogen alone, and they will also invoke new and more refined techniques to elucidate precise changes in cholesterol disposal by granulosa cells. The time to develop these additional techniques has recently (Jan. 1985) been afforded under RCDA support. Consequently, we anticipate significantly extending available studies on the nature of the regulatory effects of estradiol and on the mechanisms subserving estradiol's biological amplification of hormone action in the ovary. Such knowledge will help to clarify the significant endocrine mechanisms that prepare granulosa cells for the high rates of progesterone biosynthesis ultimately required for normal steroidogenic function of the corpus luteum. Accordingly, these investigations are likely to contribute to new approaches to fertility regulation in the human, domestic animal or endangered wild species.