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.
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