ROLE OF INTRAFOLLICULAR ACTIVIN AND FOLLISTATIN IN PCOS

卵泡内激活素和卵泡抑素在 PCOS 中的作用

• 批准号: 6583744
• 负责人: ALAN L SCHNEYER
• 金额: $ 23.61万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6583744
• 关键词: cell line; clinical research; female; fertility; follistatin; graafian follicles; granulosa cell; hormone regulation /control mechanism; human subject; inhibin; ovulation; pituitary gonadal axis; polycystic ovary syndrome

The broad goal of this project is to investigate the critical autocrine/paracrine role of the inhibin/activin/follistatin system in normal human follicular development and in women with Polycystic Ovary Syndrome (PCOS). To address the underlying defects leading to the classic PCOS ovarian appearance of numerous peripherally arranged, small follicles, we hypothesize that an excess of bioavailable activin contributes to both increased follicular development as well as developmental arrest of maturing follicles. Our approach is to obtain transvaginal follicular aspirates from well-characterized normal or PCOS volunteers, which can then be used to document the progression from an activin-B dominant to an inhibin-A dominant microenvironment suggested by previous immunohistochemical approaches. Specifically, we propose: Specific Aim 1: To delineate the role of the intrafollicular inhibin/activin/follistatin axis in the autocrine/paracrine regulation of normal folliculogenesis and ovulation in the human. Specific Aim 2. To characterize defects in inhibin/activin subunit biosynthesis, processing or dimerization in the abnormal follicular maturation observed in PCOS. Specific Aim 3. To determine the role of intrafollicular follistatin in regulating activin activity, and thereby follicular growth, in women with PCOS. Specific Aim 4. To determine the mechanism whereby FS regulates activin action at the cell surface in human granulosa cells and related cell line models. Thus, this Project strives to provide key information to facilitate the transition from bench (Specific Aim 4) to bedside (Specific Aims 2 and 3) while also providing a valuable normative database (Specific Aim 1) for analysis of PCOS and other studies of ovarian pathophysiology.

该项目的广泛目标是调查关键 在 正常的人类卵泡发育和多囊卵巢女性 综合征（PCOS）。解决导致经典的潜在缺陷 众多外围排列的PCOS卵巢外观 卵泡，我们假设过量的生物利用激活素过量 有助于增加卵泡发展以及 成熟卵泡的发展停滞。我们的方法是获得 从特征良好的正常或PCOS上抽吸的经阴道卵泡吸液 志愿者，然后可以用来记录从一个 激活素-B主导抑制蛋白A显性微环境提示 通过以前的免疫组织化学方法。具体来说，我们建议： 特定目的1：描绘出流体的作用 自分泌/旁分泌调节中的抑制素/活化素/卵泡蛋白轴 人类正常的卵泡发生和排卵。 特定目的2。表征抑制素/激活素亚基中缺陷 异常卵泡中的生物合成，加工或二聚化 在PCOS中观察到的成熟。 特定目的3。确定流体内卵泡素在 调节活化素活性，从而调节卵泡的生长 PCOS。 特定目的4。确定FS调节激活素的机制 在人颗粒细胞和相关细胞系中的细胞表面作用 型号。 因此，该项目努力提供关键信息，以促进 从长凳（特定目标4）过渡到床边（特定目标2和 3）同时还提供有价值的规范数据库（特定目的1） 用于分析PCOS和其他卵巢病理生理学研究。