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 understand the mechanisms whereby hormonal and local factors control the structure-function of the ovulatory follicle and corpus luteum in the ovary, and hence fertility, during the menstrual cycle in primates. Ongoing research is testing the hypothesis that the vital actions of the pituitary hormone, luteinizing hormone (LH) in promoting ovulation of the mature follicle and its subsequent conversion into the corpus luteum, and in controlling the functional lifespan of the corpus luteum, is either direct or indirect via local steroid action (e.g., via stimulation of progesterone [P] synthesis and P receptor expression). Because of similarities to ovarian function in women, monkeys are used in experiments where either LH and steroid hormones are depleted or steroids alone are depleted and replaced. The ovulatory follicle or corpus luteum is then removed to analyze molecular and cellular processes that are LH-dependent and either steroid/P-independent or -dependent. Gene and protein expression are analyzed for various processes, including: (1) protease enzymes that may be critical for tissue remodeling during ovulation, luteal development and luteal regression, and (2) local regulatory systems, e.g., the corticotropin-releasing hormone (CRH)/urocortins (UCN)-receptor-binding protein system. Current genome-wide analyses are identifying processes that are regulated by LH and/or steroid hormones in the follicle or corpus luteum. The activity of these processes is being manipulated, via gene knockdown or protein antagonist approaches, to elucidate their biologic relevance to primate ovarian function and cyclicity.
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