PROSTAGLANDIN SYNTHESIS AND ACTION IN THE PRIMATE CORPUS LUTEUM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项研究的目的是确定灵长类黄体(CL)内发生的负责其发展和退化的机制。从非灵长类物种获得的证据表明，前列腺素(PGs)调节黄体结构和功能，但它们在灵长类黄体生理中的作用尚未确定。初步研究表明，在灵长类CL的整个发育过程中，PGE2合成酶(PGE2合成酶2，Ptgs2；PGE2合成酶1，PTGES)和信号(PGE2受体3，PTGER3)组分的表达达到高峰。此外，在CL功能减退期之前，PGE2合成和信号成分的表达显著降低，这也与PGF2pha受体(PTGFR)的表达水平升高相一致。因此，我们将进行实验，以验证PGE2对灵长类黄体发育至关重要的假设，而PGF2pha则是黄体溶解的关键启动者。研究将评估PGE2信号在灵长类CL发育中的作用，并评估在黄体期结束时CL的消亡是否需要PGF2pha信号。通过Ptgs2选择性抑制剂阻止黄体内PG合成的方案将决定它们在CL发生中的作用。在发育中的CL中，PG合成的消融将与通过使用选择性PTGER3激动剂恢复PTGER3信号相结合。到目前为止已完成的研究表明，在排卵后立即阻止PG的合成，在黄体形成期间，会导致孕酮产生减少，黄体期缩短。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The objective of this research is to define the mechanisms occurring within the primate corpus luteum (CL) responsible for its development and regression. Evidence obtained from nonprimate species indicates that prostaglandins (PGs) regulate luteal structure-function, but their role in primate luteal physiology has not been defined. Preliminary data demonstrated that the expression of PGE2 synthesis (prostaglandin-endoperoxide synthase 2, PTGS2; PGE2 synthase-1, PTGES) and signaling (PGE2 receptor 3, PTGER3) components peak in the primate CL through the period of its development. Moreover, expression of the PGE2 synthesizing and signaling components significantly decreased preceding the period of functional regression of the CL, which also coincided with increasing levels of PGF2alpha receptor (PTGFR) expression. Thus, experiments will be performed to test the hypothesis that PGE2 actions are critical for primate luteal development, while PGF2alpha serves as a critical initiator of luteolysis. Studies are proposed that will assess the role PGE2 signaling plays in the development of the primate CL and evaluate whether PGF2alpha signaling is required for the demise of the CL at the end of the luteal phase. Protocols blocking intraluteal PG synthesis via a PTGS2 selective inhibitor will determine their role in CL development. The ablation of PG synthesis in the developing CL will be combined with the restoration of PTGER3 signaling through the use of a selective PTGER3 agonist. Studies completed to date revealed that blocking PG synthesis immediately following ovulation, through the period of corpus luteum formation, leads to a reduction in progesterone production and a shortened luteal phase.