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激增盘中运动级联 在卵泡壁的显着破裂中达到高潮的事件 顶点和随后的卵母细胞 - 肿瘤复合物的释放。尽管有它 对于生殖和生育至关重要，尽管数十年 研究，我们对监管的了解有很多差距 排卵过程。许多监管机构和途径已被认为是 参与哺乳动物排卵，但先前研究的结果已经 强调了孕酮和前列腺素（PGS）的基本作用。牛 提供了一个理想的动物模型来研究 血周期。我们已经验证了一种诱导外周围的模型 牛的卵泡发育，我们现在建议使用它来测试 关于这两个排卵及其受体的关键调节剂的假设。在 特定目的1和2，合成的时序，细胞位点，生物合成 PG合成的途径和荷尔蒙调节 将被检查。要检验的假设是theca和granulosa 细胞对卵石前LH/FSH激增反应，PG增加 生产，由孕酮激发诱导的升高介导 通过从PGE2还原来诱导PGF2A合成。在特定目标3中，我们将 检验孕酮对前列腺素的影响的假设 卵泡周围的产生至少部分介导 通过孕激素诱导的催产素的增加。虽然PG是必不可少的 对于排卵，几乎对PG受体的表达一无所知 在卵路周期。在特定的目标4中，时间表的时间表达 牛卵泡中PGF2Alpha受体的mRNA将是 决定。受体的mRNA是协调表达的假设 随着PG合成的升高，并将其定位于 卵巢卵泡将进行测试。特定目标5旨在测试 假设LWFSH激增诱导孕酮受体（PR） 卵泡卵泡的卵泡细胞，这些受体介导 孕酮对PG产生的影响。这些实验将在一起 提供有关这些调节和关系之间的新知识 排卵及其受体的两个必不可少的介体。