DIFFERENTIATION IN HUMAN GRANULOSA CELLS

人颗粒细胞的分化

• 批准号: 3314084
• 负责人: MARY L. POLAN
• 金额: $ 20.53万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3314084
• 关键词: adenosine; cellular pathology; cyclic AMP; estradiol; estriol; estrone; follicle stimulating hormone; gonadotropins; graafian follicles; hormone binding protein; hormone receptor; hormone regulation /control mechanism; human tissue; laboratory rat; luteinizing hormone; membrane activity; prolactin; radioimmunoassay; radiotracer; tissue /cell culture

The purpose of this investigation is to examine periovulatory changes in the human follicle to better define the sequence of events surrounding ovulation and culminating in the differentiation of an adequately funtioning corpus luteum. Most of our knowledge about the sequence of steroidogenic and receptor-mediated events surrounding ovulation is derived from animal investigations and extended by analogy to the human. Increasing experimental evidence suggests that this may be a faulty analogy. Specifically, we propose to evaluate the ability of adenosine, androgens and prolactin to modulate gonadotropin effects in both pre- and periovulatory cultured human granulosa cells. Adenosine amplification of FSH- and LH-mediated cAMP and steroid production in preovulatory cells will be examined as well as the relationship of follicular fluid purines to folliculogenesis. Androgen-induced inhibitory effects on steroidogenesis and LH-receptor appearance will be investigated in both preovulatory cells and periovulatory granulosa-luteal cells. Finally, inhibition of luteal development by prolactin will be assessed. In addition to steroidogenesis we will examine granulosa-luteal cells to determine the role of LH, prolactin and androgen in the expression of LH-receptors as a measure of adequate luteal differentiation. The sensitivity of luteal LH-receptor appearance to inhibitors of both protein and RNA synthesis will be determined. This proposal is designed to answer the follwoing questions. In addition to gonadotropins are there other important modulators of steroidongenesis, such as adenosine, androgen and prolactin, which affect human follicular development and differentiation? What role do known putative effectors of ovarian function such as gonadotropins, prolactin, Ca2++ mediated-phosphorylation and protein or RNA synthesis play in periovulatory luteal differentiation as manifested by the appearance of LH-receptors and steroidogenesis? Answers to these questions will illuminate the events surrounding ovulation and luteal differentation in the human ovary which are critical to the regulation of our fertility and reproduction.

这项调查的目的是检查排卵期的变化。 人类卵泡更好地定义周围事件的顺序 排卵和在分化中达到顶峰 黄体功能正常。我们对这一序列的大部分了解 围绕排卵的类固醇激素和受体介导的事件是衍生的 从动物研究，并通过类推扩展到人类。 越来越多的实验证据表明，这可能是一种错误的 打个比方。具体地说，我们建议评估腺苷的能力， 雄激素和催乳素对促性腺激素作用的调节 排卵期培养的人颗粒细胞。腺苷扩增 卵泡刺激素和促黄体生成素介导的排卵前细胞产生cAMP和类固醇 以及卵泡液嘌呤与 卵泡发生。雄激素对类固醇合成的抑制作用 将在两个排卵前细胞中研究促黄体生成素受体的外观 排卵周颗粒黄体细胞。最后，黄体抑制 将对催乳素的发育进行评估。 除了类固醇激素的生成，我们还将检查颗粒黄体细胞以 测定促黄体生成素、催乳素和雄激素在卵泡刺激素表达中的作用 促黄体生成素受体作为黄体分化的一种衡量标准。这个 黄体促黄体激素受体的出现对两种蛋白抑制剂的敏感性 核糖核酸的合成将被确定。这项提议旨在回答 接下来的问题。除了促性腺激素，还有其他的吗？ 类固醇生成的重要调节剂，如腺苷、雄激素和 催乳素，哪些影响人类卵泡的发育和分化？ 已知的卵巢功能假定效应物，如 促性腺激素、催乳素、钙离子介导的磷酸化和蛋白质或RNA 合成在排卵期黄体分化中的作用 黄体生成素受体的出现与类固醇激素的生成？这些问题的答案 将阐明围绕排卵和黄体分化的事件 在人类卵巢中对调节我们的生育能力至关重要 和繁衍。