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Regulation of Prostaglandins in Periovulatory Follicles

排卵周围卵泡中前列腺素的调节

基本信息

批准号：
6846052
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
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-02-01 至 2007-01-31
项目状态：
已结题

项目摘要

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激增启动级联反应的事件，在卵泡壁的显着破裂达到高潮，卵母细胞-卵丘复合体的顶端和随后的释放。尽管对生殖和生育至关重要，尽管几十年来研究，我们对监管的认识存在许多空白，排卵过程许多调节器和途径被假设为参与哺乳动物排卵，但以前的研究结果表明，强调了孕酮和前列腺素（PGs）的重要作用。牛提供了一个理想的动物模型，研究复杂的事件，围排卵期我们已经验证了诱导排卵周期的模型，牛的卵泡发育，我们现在建议用它来测试关于这两个关键的排卵调节器及其受体的假说。在具体目标1和2，合成的时间、细胞位点、生物合成途径和激素调节排卵期PG合成增加将被审查。有待检验的假设是，细胞对排卵前LH/FSH激增的反应是PG增加，生产，介导的激增引起的孕酮上升，这反过来又通过还原PGE 2诱导PGF 2a合成。在第三阶段，我们将检验孕酮对前列腺素的影响排卵期卵泡的产生至少部分是由导致催产素水平升高虽然PG是必不可少的对于排卵，几乎对PG受体的表达一无所知，在排卵期。在具体目标4中，牛排卵期卵泡中PGF 2 α受体的mRNA将被测定该受体的mRNA协同表达的假设随着PG合成的增加，它定位于卵泡膜细胞，将检测排卵期卵泡。具体目标5旨在测试假设LWFSH激增诱导孕酮受体（PR），排卵期卵泡的卵泡细胞，这些受体介导孕酮对PG产生的影响。这些实验将提供关于这些规则和关系的新知识，排卵的两种基本介质及其受体。