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STEROID HORMONE METABOLISM

类固醇激素代谢

基本信息

批准号：
3310780
负责人：
KENNETH J. RYAN
金额：
$ 21.33万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-05-01 至 1990-04-30
项目状态：
已结题

项目摘要

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.

这项研究计划涉及的因素，控制或与卵巢类固醇激素代谢和卵泡生长有关，发展将探讨三个感兴趣的领域：1。 5 α-还原酶活性。我们实验室的研究表明， α-减少雄激素代谢作为卵泡生长的决定因素，闭锁人类和仓鼠颗粒细胞具有显著的5 α-还原酶活性。从闭锁卵泡中提取的人体细胞。 DHT 抑制大鼠颗粒细胞增殖。 5的特异性抑制剂 α-还原酶活性将用于确定其对卵巢癌的影响。功能;具体而言，体内卵泡生长和发育，颗粒细胞增殖和芳香化酶活性。 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。我们建议的研究将研究鞘血管生成因子与控制合成、表征、与黄体血管生成因子的关系，以及卵泡生长和闭锁。3. 物质P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SP和NT 物种卵巢SP和NT含量在周期中变化，在卵巢内受到不同程度的干扰。鉴于最近在卵巢和睾丸中发现了GhRH的作用，我们建议探索 SP和NT在生殖系统中的意义。 P物质和卵巢中神经降压素的含量和分布以及垂体前叶将在各种生殖状态下确定，家兔和仓鼠，以及健康和闭锁的人类卵泡。的这两种肽在类固醇生成和滤泡中的可能作用将通过体外和体内研究探索生长。的这项研究将帮助我们了解参与的基本机制。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。