PROSTAGLANDIN SYNTHESIS AND ACTION IN THE PRIMATE CORPUS LUTEUM

灵长类黄体中前列腺素的合成和作用

• 批准号: 8357742
• 负责人: Jon D Hennebold
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357742
• 关键词: Ablation; Agonist; Data; Development; Dinoprost; Dinoprostone; Funding; Grant; Luteal Phase; Luteolysis; National Center for Research Resources; Ovulation; PTGS2 gene; Physiology; Play; Primates; Principal Investigator; Production; Progesterone; Prostaglandin E Receptor; Prostaglandins; Protocols documentation; Research; Research Infrastructure; Resources; Role; Signal Transduction; Source; Structure; Testing; United States National Institutes of Health; corpus luteum; cost; cyclooxygenase 2; inhibitor/antagonist; primate development; receptor; research study; restoration

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 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灵长类黄体 (CL) 中负责其发育和退化的机制。从非灵长类动物获得的证据表明前列腺素（PG）调节黄体结构功能，但它们在灵长类黄体生理学中的作用尚未明确。初步数据表明，PGE2 合成（前列腺素内过氧化物合酶 2，PTGS2；PGE2 合酶-1，PTGES）和信号（PGE2 受体 3，PTGER3）成分的表达在灵长类 CL 的发育过程中达到峰值。此外，在 CL 功能退化之前，PGE2 合成和信号成分的表达显着下降，这也与 PGF2α 受体 (PTGFR) 表达水平的增加相一致。因此，将进行实验来检验以下假设：PGE2 作用对于灵长类黄体发育至关重要，而 PGF2α 是黄体溶解的关键引发剂。拟议的研究将评估 PGE2 信号传导在灵长类 CL 发育中的作用，并评估 PGF2α 信号传导是否是 CL 在黄体期结束时死亡所必需的。通过 PTGS2 选择性抑制剂阻断黄体内 PG 合成的方案将决定它们在 CL 发展中的作用。正在发育的 CL 中 PG 合成的消除将与通过使用选择性 PTGER3 激动剂恢复 PTGER3 信号传导相结合。迄今为止完成的研究表明，在排卵后、黄体形成期间立即阻断 PG 合成，会导致黄体酮生成减少和黄体期缩短。