Protease Expression and Action in the Primate Ovary

描述(申请人提供)：排卵后，黄体(CL)从破裂的卵泡中形成，分泌孕酮(P)以允许宫内妊娠。在非可育周期中，P的产量下降，CL倒退，确保生殖潜力的恢复。基质金属蛋白酶表达和活性的变化与CL的形成和消退所需的实质性组织重塑有关。然而，基质金属蛋白酶的动态调节以及基质金属蛋白酶在CL发生或消退中的具体作用尚不清楚。最近的研究发现，促性腺激素和排卵周围卵泡中的局部P依赖过程，包括对特定的MMPs及其组织抑制物(TIMPs)的调节。因此，本实验旨在验证以下假设：(1)促性腺激素和类固醇，尤其是P。在月经周期中调节CL中的MMPs和TIMPs，以及(2)MMPs对灵长类CL的发育和退化是必不可少的。分子和生化技术，如‘实时’聚合酶链式反应，蛋白质分析，免疫组织化学和酵素图谱，将被用来检测在黄体寿命和激素消融/替代期间MMPs和跛行的变化。这项研究将为我们提供第一个全面的关于CL中基质金属蛋白酶的调节和功能的研究，进一步加深我们对不孕症黄体发育不全的认识和治疗，并可能为女性推荐新的避孕方法。

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.