Protease Expression and Action in the Primate Ovary

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DESCRIPTION (provided by applicant): Following ovulation, the corpus luteum (CL) forms from the ruptured follicle, secreting progesterone (P) to permit intrauterine pregnancy. In nonfertile cycles, P production subsides and the CL regresses, ensuring return of reproductive potential. Changes in matrix metalloproteinase (MMP) expression and activity are associated with the substantial tissue remodeling required for both formation and regression of the CL. However, the regulation of MMP dynamics, plus the specific roles of MMPs in CL development or regression are unknown. Recent studies have identified gonadotropin and local Pdependent processes in the periovulatory follicle, including regulation of specific MMPs and their tissue inhibitors (TIMPs). Therefore the current experiments were designed to test the hypothesis that (1) gonadotropins and steroids, notably P. regulate MMPs and TIMPs in the CL during the menstrual cycle, and (2) MMPs are essential for CL development and regression in primates. Molecular and biochemical techniques, such as 'real time' PCR, Western analysis, immunohistochemistry, and zymography will be employed to detect changes in MMPs and lIMPs throughout the luteal lifespan and during hormone ablation/replacement. The proposed studies will provide the first comprehensive examination of MMP regulation and function in the CL, further our knowledge of and treatment for luteal phase defects in infertility, and may recommend novel forms of contraception for women.