PGRMC1介导孕酮抗氧化的作用及其机制的研究

项目名称： PGRMC1介导孕酮抗氧化的作用及其机制的研究

项目编号： No.81200418

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 袁晓华

作者单位： 西安交通大学

项目金额： 23万元

中文摘要： 孕酮膜受体（PGRMC1）对卵泡发育和甾体激素合成相关的p450酶类活性起着重要的调节作用，PGRMC1突变导致卵巢颗粒细胞凋亡率增加并与卵巢早衰密切相关。我们前期发现在卵巢颗粒细胞中孕酮具有抗氧化作用，其作用依赖于PGRMC1的表达，但具体分子机制有待阐明。 本课题拟以颗粒细胞SIGC为研究对象，利用孕酮及氧化剂结合基因干涉和转染技术探索PGRMC1介导孕酮抗氧化作用的分子机制；以大鼠颗粒细胞为研究对象，用LH诱导孕酮分泌，探索甾体激素合成过程中，PGRMC1对线粒体上介导甾体激素和活性氧（ROS）生成的关键酶p450scc的调节作用，及这种调节作用对氧化还原和甾体激素合成的影响。实施本项目将有助于深入认识孕酮抗凋亡背后的机制，还可为阐明卵巢早衰的发病机制及治疗提供新的实验室证据。

中文关键词： 孕酮膜受体；抗氧化；孕酮；卵巢颗粒细胞；卵巢早衰

英文摘要： Premature ovarian failure was characterized by decrease in ovarian follicle reserve or excessive depletion of primordial follicles. Abnormalities in primordial follicle assembly, arrest, and development can cause premature ovarian failure. A number of factors participated in the regulation of follicles development. Studies had showed that progesterone inhibited follicles assembly and mediated anti-apoptotic action in granulosa cells .The effect of progesterone combined with PGRMC1 (progesterone receptor membrane component 1) on regulation follicles development was highlighted in recent years. The expression level of PGRMC1 of patients with premature ovarian failure was decline. Missense mutation of PGRMC1 in the cytochrome b5 domain attenuated the the anti-apoptotic ability of progesterone in ovarian cells and abolished the binding of PGRMC1 to cytochrome P450 7A1 (CYP7A1) related with steroidogenesis. The anti- apoptotic action of progesterone was mediated by PGRMC1. Our previous study founded that in addition of anti-apoptotic action, progesterone also performed anti-oxidative function in granulosa cells. Oxidative damage is one of the mechanisms of apoptosis in granulosa cells. We conjectured that the anti-oxidative function of progesterone may be also mediated by PGRMC1. Further study indicated that the anti

英文关键词： PGRMC1；anti-oxidative；progesterone；granuloa cell；premature ovarian failure