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 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 gonadotropic 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 [PR] expression). Because of similarities to ovarian function in women, monkeys are used in experiments where either LH and steroid hormones are depleted (using a gonadotropin-releasing hormone antagonist) or steroids alone are depleted (using a steroid synthesis inhibitor), and replaced. The ovulatory follicle or corpus luteum is then removed from control and treated monkeys to analyze molecular and cellular processes that are LH-dependent and either steroid/P-independent or -dependent. Gene (mRNA) and protein (levels and activity) expression are analyzed for various processes, including: (1) protease enzymes that may be critical for tissue remodeling during ovulation, luteal development and luteal regression, e.g., matrix metalloproteases and caspases, and (2) local paracrine or autocrine regulatory systems, e.g., the corticotropin-releasing hormone (CRH)/urocortin (UCN)-receptor-binding protein system. The activity of these processes will then be manipulated, via gene knockdown or protein antagonist approaches, to elucidate their biologic relevance to primate ovarian function and cyclicity.
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