Protease Expression and Action in the Primate Ovary

描述（申请人提供）：排卵后，黄体（CL）由破裂的卵泡形成，分泌孕酮（P），使子宫内妊娠。在非生育周期中，P生产下降，CL退化，确保生殖潜力的恢复。基质金属蛋白酶（MMP）表达和活性的变化与CL形成和消退所需的实质性组织重塑相关。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P依赖性过程中的围排卵卵泡，包括调节特定的基质金属蛋白酶及其组织抑制剂（TIMPs）。因此，目前的实验旨在验证以下假设：（1）促性腺激素和类固醇，特别是P.调节月经周期期间CL中的MMP和TIMP，以及（2）MMP对灵长类动物的CL发育和消退至关重要。将采用分子和生物化学技术，如“真实的时间”PCR、Western分析、免疫组织化学和酶谱法来检测整个黄体寿命期间和激素消融/替代期间MMP和IMP的变化。拟议的研究将提供第一次全面检查MMP的调节和功能的CL，进一步了解和治疗不孕症的黄体期缺陷，并可能推荐新的形式的妇女避孕。

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.