Regulation of Prostaglandins in Periovulatory Follicles

排卵周围卵泡中前列腺素的调节

• 批准号: 6693380
• 负责人: JOANNE E. FORTUNE
• 金额: $ 25.04万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693380
• 关键词: cell cell interaction; corpus luteum; cow; eicosanoid metabolism; fatty acid biosynthesis; follicle stimulating hormone; graafian follicles; granulosa cell; hormone regulation /control mechanism; in situ hybridization; luteinizing hormone; messenger RNA; ovulation; oxytocin; progesterone; progesterone receptors; prostaglandin E; prostaglandin endoperoxide synthase; prostaglandin receptor; prostaglandins; radioimmunoassay; receptor expression; reproductive development; tissue /cell culture

DESCRIPTION (provided by applicant): The LH/FSH surge sets in motion a cascade of events that culminates in the remarkable rupture of the follicular wall at the apex and the subsequent release of the oocyte-cumulus complex. Despite its critical importance to reproduction and fertility, and despite decades of research, there are many gaps in our knowledge of the regulation of the ovulatory process. Many regulators and pathways have been hypothesized to be involved in mammalian ovulation, but results of previous studies have highlighted essential roles for progesterone and prostaglandins (PGs). Cattle provide an ideal animal model for studying the complex events of the periovulatory period. We have validated a model for inducing periovulatory follicular development in cattle and we now propose to use it to test hypotheses about these two key regulators of ovulation and their receptors. In Specific Aims 1 and 2, the timing, cellular site(s) of synthesis, biosynthetic pathway, and hormonal regulation of the periovulatory increase in PG synthesis will be examined. The hypothesis to be tested is that both theca and granulosa cells respond to the preovulatory LH/FSH surge with an increase in PG production, mediated by the surge-induced rise in progesterone, which in turn induces PGF2a synthesis, via reduction from PGE2. In Specific Aim 3 we will test the hypothesis that the effects of progesterone on prostaglandin production by the periovulatory follicle are at least partially mediated through progesterone-induced increases in oxytocin. Although PGs are essential for ovulation, virtually nothing is known about the expression of PG receptors during the periovulatory period. In Specific Aim 4, the temporal expression of mRNA for PGF2alpha receptor in bovine periovulatory follicles will be determined. The hypothesis that mRNA for the receptor is expressed coordinately with the rise in PG synthesis and, is localized to the theca cells of the periovulatory follicle will be tested. Specific Aim 5 is designed to test the hypothesis that the LWFSH surge induces progesterone receptor (PR) in follicular cells of the periovulatory follicle and that these receptors mediate progesterone's effects on PG production. Together these experiments will provide new knowledge about the regulation of, and relationship between, these two essential mediators of ovulation and their receptors.

描述（由申请人提供）：LH/FSH 激增启动级联 最终导致毛囊壁显着破裂的事件 卵母细胞-卵丘复合体的顶点和随后的释放。尽管其 对生殖和生育力至关重要，尽管几十年来 研究表明，我们对监管的认识还存在很多差距。 排卵过程。许多调节剂和途径被假设为 参与哺乳动物的排卵，但之前的研究结果表明 强调了黄体酮和前列腺素 (PG) 的重要作用。牛 为研究复杂事件提供了理想的动物模型 围排卵期。我们已经验证了诱导排卵期的模型 牛的卵泡发育，我们现在建议用它来测试 关于排卵的这两个关键调节因子及其受体的假设。在 具体目标 1 和 2、合成时间、细胞位点、生物合成 PG 合成围排卵增加的途径和激素调节 将接受检查。要检验的假设是卵泡膜和颗粒细胞 细胞对排卵前 LH/FSH 激增做出反应，PG 增加 产生，由激增引起的黄体酮升高介导，这反过来又 通过还原 PGE2 诱导 PGF2a 合成。在具体目标 3 中，我们将 检验黄体酮对前列腺素影响的假设 排卵期卵泡的产生至少部分是介导的 通过黄体酮引起的催产素增加。虽然PG是必不可少的 对于排卵，实际上对 PG 受体的表达一无所知 在排卵期期间。在具体目标 4 中，时间表达式 牛排卵期卵泡中 PGF2α 受体的 mRNA 将被 决定。受体 mRNA 协调表达的假设 随着 PG 合成的增加，并且定位于卵泡膜细胞 将测试排卵期卵泡。具体目标 5 旨在测试 假设 LWFSH 激增会诱导孕激素受体 (PR) 排卵期卵泡的卵泡细胞以及这些受体介导的 黄体酮对 PG 产生的影响。这些实验将共同 提供有关这些因素的调节及其之间关系的新知识 排卵的两种重要介质及其受体。