PROSTAGLANDIN SYNTHESIS AND ACTION IN THE PRIMATE CORPUS LUTEUM

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心赠款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 本研究的目的是确定发生在灵长类动物黄体（CL）负责其发展和退化的机制。从非灵长类动物中获得的证据表明，前列腺素（PGs）调节黄体的结构-功能，但其在灵长类动物黄体生理学中的作用尚未确定。初步数据表明，在灵长类动物CL中，PGE 2合成（前列腺素内过氧化物合成酶2，PTGS 2; PGE 2合成酶-1，PTGES）和信号传导（PGE 2受体3，PTGER 3）组分的表达在其发育期间达到峰值。此外，前列腺素E2合成和信号传导成分的表达显着下降之前的CL，这也与前列腺素F2 α受体（PTGFR）表达水平的增加相一致的功能衰退期。因此，将进行实验以检验PGE 2作用对灵长类动物黄体发育至关重要，而PGF 2 α作为黄体溶解的关键引发剂的假设。建议开展研究，评估PGE 2信号在灵长类CL发展中的作用，并评估PGF 2 α信号是否是黄体期结束时CL死亡所需的。通过PTGS 2选择性抑制剂阻断输卵管内PG合成的方案将决定其在CL发展中的作用。发展中CL中PG合成的消融将与通过使用选择性PTGER 3激动剂恢复PTGER 3信号传导相结合。迄今为止完成的研究表明，在排卵后立即阻断PG合成，通过黄体形成期，导致孕酮产生减少和黄体期缩短。

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.