PROSTAGLANDIN RECEPTOR REGULATION IN THE CORPUS LUTEUM

黄体中前列腺素受体的调节

• 批准号: 2673823
• 负责人: MILO C WILTBANK
• 金额: $ 9.62万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673823
• 关键词: calcium flux; cell differentiation; corpus luteum; cow; enzyme induction /repression; female; gene induction /repression; granulosa cell; hormone regulation /control mechanism; hydroxysteroid dehydrogenases; luteinizing hormone; menstrual cycle; messenger RNA; ovulation; oxytocin; polymerase chain reaction; progesterone; prostaglandin F; prostaglandin endoperoxide synthase; prostaglandin receptor; protein biosynthesis; protein kinase A; receptor expression; sheep; tissue /cell culture

Prostaglandins (PG) have an essential role in regulating ovarian function including key aspects of ovulation, luteinization, and luteal regression. Despite this central role in reproductive physiology the temporal and cellular patterns of expression for the PG receptors, as well as the hormonal regulation of this expression, have not been defined. With the recent cloning of the cDNAs for the various subtypes of PGE and PGF/2alpha receptors, an analysis of both the protein and mRNA for these receptors is possible. We have validated highly sensitive and quantitative assays for the PGF/2alpha receptor mRNA and protein as well as the measuring PGF/2alpha responsiveness. The research proposed in this application is designed to evaluate the mechanisms involved in expression of the PGF/2alpha receptors and responsiveness during luteinization and luteolysis. Our working hypotheses for these studies is that the LH surge, or other aspects of the luteinization process, induce the expression of PGF/2alpha receptors and PG-responsive intracellular pathways, thus, establishing the cellular mechanisms for ovulation, luteinization, and regression of the corpus luteum. The Specific Aims are: 1) Characterize the temporal pattern for the in vivo expression of PGF/2alpha receptors during late follicular and early luteal development. 2) Determine the role of cAMP-dependent protein kinase, progesterone, and de novo protein synthesis in the differentiation of PGF/2alpha responsiveness in cultured follicular cells. 3) Determine whether small luteal cells can be induced by forskolin or hCG to express FP receptors, a property indicative of the large luteal cell phenotype. Determine the intracellular effector systems involved in PGF/2alpha-induced stimulation of mRNA for PGH synthase-2 and inhibition of mRNA for the PGF/2alpha receptor. 4) Determine the response of early and mid-cycle corpora lutea to PGF/2alpha in terms of down regulation of PGF/2alpha receptors, secretion of oxytocin, induction of mRNA for PGHS-2, and inhibition of expression of mRNA for 3beta-Hydroxysteroid Dehydrogenase. These studies will advance our knowledge of physiologic, intracellular, and molecular mechanisms regulating the expression of mRNA, protein, and intracellular response pathways for the PGF/2alpha receptor. This will not only advance our current knowledge of reproductive physiology, but will allow for the rational development of contraceptives or infertility treatments that target prostaglandin action in the ovary.

前列腺素（PG）在调节卵巢功能中具有重要作用 包括排卵、黄体化和黄体退化的关键方面。 尽管在生殖生理学中起着核心作用， PG受体的细胞表达模式，以及 这种表达的激素调节尚未确定。 与 最近克隆了PGE和PGF/2 α各种亚型的cDNA 受体，对这些受体的蛋白质和mRNA的分析是 可能 我们已经验证了高灵敏度和定量分析， PGF/2 α受体mRNA和蛋白质水平的测定 PGF/2 α反应性。 本申请中提出的研究是 旨在评估参与表达的机制， PGF/2 α受体和黄体化过程中的反应性， 黄体溶解 我们对这些研究的工作假设是，LH 激增，或其他方面的叶黄素化过程中，诱导 PGF/2 α受体的表达和PG反应性细胞内 因此，建立排卵的细胞机制， 黄体化和黄体退化。 具体目标 是： 1)表征体内表达的时间模式， PGF/2 α受体在卵泡晚期和黄体早期发育中的作用 2)确定cAMP依赖性蛋白激酶，孕酮， PGF/2 α分化过程中的蛋白质从头合成 培养的滤泡细胞的反应性。 3)确定小黄体细胞是否可以诱导毛喉素或 hCG表达FP受体，这是大黄体的一个标志。 细胞表型 确定参与的细胞内效应系统 PGF/2 α诱导的PGH合酶-2 mRNA的刺激和抑制 PGF/2 α受体的mRNA。 4)确定周期早期和中期黄体对 PGF/2 α在下调PGF/2 α受体、分泌 催产素，诱导PGHS-2的mRNA，并抑制 3 β-羟基类固醇脱氢酶的mRNA。 这些研究将推进我们对生理、细胞内、 以及调节mRNA、蛋白质和 PGF/2 α受体的细胞内反应途径。 这将 不仅推进了我们现有的生殖生理学知识， 将允许避孕药或不孕症的合理发展 针对卵巢中前列腺素作用的治疗。