PROSTAGLANDIN SYNTHESIS AND ACTION IN THE PRIMATE CORPUS LUTEUM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的长期目标是确定灵长类动物黄体（CL）内发生的机制，是其发展和退化的关键。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酶2，PTGS 2;微粒体PGE 2合酶-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，PGE 2合成和信号传导组分的表达在CL的功能消退期之前显著降低，这也与PGF 2a受体（PTGFR）表达水平的增加相一致。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 2a作为黄体溶解的关键引发剂的假设。研究建议，将评估的作用PGE 2信号在灵长类动物CL的发展，并评估是否需要PGF 2a信号在黄体期结束的CL的消亡。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。迄今为止的进展包括动物的初始筛选和媒介物治疗，以准备给予选择性PTGS 2抑制剂和PGF 2a拮抗剂。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objective of this research is to define the mechanisms occurring within the primate corpus luteum (CL) that are critical 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 have not been defined. Preliminary data demonstrated that the expression of PGE2 synthesis (prostaglandin-endoperoxide synthase 2, PTGS2; microsomal 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 PGF2a receptor (PTGFR) expression. Thus, experiments will be performed to test the hypothesis that PGE2 actions are critical for primate luteal development, while PGF2a 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 PGF2a 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. Progress to date includes the initial screening and vehicle treatment of animals in preparation for administration of a selective PTGS2 inhibitor and a PGF2a antagonist.