STEROID HORMONE METABOLISM

这项研究建议涉及控制或被 与卵巢类固醇激素代谢和卵泡生长有关 发展。将探索三个感兴趣的领域：1.5 α-还原酶活性。我们实验室的工作表明有5人 α-雄激素代谢降低是卵泡生长和发育的决定因素 闭锁。人和金黄地鼠颗粒细胞有显著的5 α-还原酶活性。来自闭锁卵泡的人类细胞。分布式哈希表 抑制大鼠颗粒细胞增殖。5的特异性抑制物 将使用α-还原酶活性来确定其对卵巢的影响 功能；具体地说，体内卵泡的生长和发育 颗粒细胞体外增殖和芳香酶活性。2. 血管生成因子。我们有初步证据表明卵泡膜 细胞在体外产生一种血管生成因子。血管生成被认为是 是卵泡生长的关键过程。我们建议的研究将 探讨鞘内血管生成因子在防治高血压病中的作用 合成、表征及其与黄体血管生成因子的关系 卵泡生长和闭锁。3.P物质和神经降压素。我们有 确定在至少4种哺乳动物的卵巢中发现了SP和NT 物种。仓鼠卵巢中SP和NT的含量在周期和 在卵巢内受到不同程度的干扰。鉴于最近 已发现GHRH在卵巢和睾丸中的作用，我们建议探索 SP、NT在生殖系统中的意义P物质和 神经降压素在卵巢中的含量及其在卵巢中的分布 垂体前叶将在不同的生殖状态下确定 兔和仓鼠，以及健康和闭锁的人卵泡中。这个 这两种多肽在类固醇合成和滑膜中的可能作用 生长将通过体外和体内研究来探索。这个 拟议的研究将帮助我们了解 卵巢功能，特别是闭锁，血管动力学和 卵巢的神经内分泌控制。

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.