黄体生成素受体的选择性剪切在多囊卵巢综合症发病中的作用机制研究

项目名称： 黄体生成素受体的选择性剪切在多囊卵巢综合症发病中的作用机制研究

项目编号： No.81200416

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： 韩兵

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 多囊卵巢综合症(PCOS)是一种育龄妇女最常见的疾患，往往同时伴有胰岛素抵抗，使发生糖尿病和心血管疾病的危险性显著升高。黄体生成素受体(LHR)作为一种具有7次跨膜结构的G蛋白耦联受体，在体内存在选择性剪切，出现多种剪切异构体。既往的研究表明LHR与PCOS的发病密切相关，而选择性剪切作为疾病的发病因素得到了越来越多的重视。我们通过realtime PCR发现，正常人与PCOS患者卵泡膜细胞中LHR剪切异构体存在差异性表达。因此，我们推测卵泡膜细胞内LHR的选择性剪切处于一种平衡状态，各种剪切异构体的表达存在一定的比例，而PCOS患者中这种平衡状态被打破，导致卵巢雄激素合成增多，出现高雄激素血症的临床表现。我们拟从剪切结合位点以及剪切因子的角度来研究导致选择性剪切异常的机制。最后，通过寻找影响选择性剪切的因素，可以作为潜在靶点纠正PCOS患者高雄激素血症。

中文关键词： 黄体生成素；剪切异构体；多囊卵巢综合症；单核苷酸多态性；基因型

英文摘要： Polycystic ovary syndrome (PCOS) is the most common disorder in the childbearing age of women, which is often accompanied by insulin resistance and significantly increased the risk of diabetes and cardiovascular disease. As a seven-transmembrane G protein-coupled receptor, luteinizing hormone receptor (LHR) has a variety of isomers which is produced by in vivo alternative splicing. Previous studies have shown that the incidence of PCOS is closely related to LHR, and alternative splicing as a cause of the disease attract more and more attention. In our study, we found that LHR isoforms is differentially expressed in theca cells of normal subjects and patients with PCOS with Realtime PCR. Therefore, we speculate that alternative splicing of LHR in theca cells is in a state of equilibrium and the variety of isoforms exist in a certain proportion. However, in PCOS patients, this balance was broken, which resulting in increased ovarian androgen synthesis and the clinical manifestations of hyperandrogenism. So, we intend to study the mechanism of abnormal splicing from the perspective of splicing binding sites and the splicing factors. Finally, by looking for factors affect alternative splicing, it can be used as a potential target to control hyperandrogenism in PCOS.

英文关键词： LHR；splicing variant；PCOS；SNP；genotype