Protease Expression and Action in the Primate Ovary

描述（由申请人提供）：排卵后，黄体（CL）从破裂的卵泡形成，分泌黄体酮(P)，允许宫内妊娠。在非生育期，磷产量下降，CL退化，确保生殖潜能的恢复。基质金属蛋白酶（MMP）表达和活性的变化与CL形成和消退所需的大量组织重塑有关。然而，MMP动力学的调节以及MMP在CL发展或消退中的具体作用尚不清楚。最近的研究已经确定了促性腺激素和局部依赖过程在卵泡周围，包括调节特异性MMPs和它们的组织抑制剂（TIMPs）。因此，本实验旨在验证以下假设：(1)促性腺激素和类固醇，特别是P.在月经周期调节CL中的MMPs和TIMPs； (2) MMPs对灵长类CL的发育和消退至关重要。分子和生化技术，如“实时”PCR、Western分析、免疫组织化学和酶谱法，将被用于检测黄体整个生命周期和激素消融/替代期间MMPs和lIMPs的变化。拟议的研究将首次全面检查MMP在CL中的调节和功能，进一步了解和治疗不孕症的黄体期缺陷，并可能为女性推荐新的避孕方式。

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.