DIFFERENTIATION IN HUMAN GRANULOSA CELLS

这项研究的目的是检查排卵期的变化， 更好地定义人类卵泡周围的事件序列， 排卵和最终分化的一个充分 黄体功能 我们对基因序列的大部分了解 类固醇生成和受体介导的排卵过程 从动物研究中得出，并通过类比扩展到人类。 越来越多的实验证据表明，这可能是一个错误的 类比。 具体来说，我们建议评估腺苷的能力， 雄激素和催乳素调节促性腺激素的作用， 排卵期培养的人颗粒细胞。 腺苷扩增 FSH和LH介导的排卵前细胞中cAMP和类固醇的产生将 以及卵泡液嘌呤与 卵泡发生 雄激素诱导的类固醇生成抑制作用 和LH受体的外观将在两个排卵前细胞进行研究 和排卵期颗粒黄体细胞。 最后，抑制黄体功能 将评估催乳素引起的发育。 除了类固醇生成，我们将检查颗粒黄体细胞， 确定LH，催乳素和雄激素在表达中的作用， LH受体作为衡量黄体充分分化的指标。 的 黄体LH受体对两种蛋白抑制剂的敏感性 RNA合成将被确定。 该提案旨在回答 以下问题。 除促性腺激素外， 类固醇生成的重要调节剂，如腺苷、雄激素和 催乳素，哪些影响人类卵泡发育和分化？ 已知的卵巢功能效应因子， 促性腺激素、催乳素、Ca2++介导的磷酸化和蛋白质或RNA 促排卵激素在排卵期黄体分化中的作用 LH受体的出现和类固醇生成？ 这些问题的答案 将阐明围绕排卵和黄体分化的事件 对调节我们的生育能力至关重要 和繁殖。

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.