GPR1信号系统在高雄激素引起的多囊卵巢综合征中作用机制的研究

多囊卵巢综合征（PCOS）与高雄激素和肥胖密切相关，但机制尚未阐明。有临床数据显示，脂肪因子chemerin在PCOS患者血清中显著升高。我们已首次报道了chemerin对睾酮分泌有抑制作用。本项目拟在前期工作的基础上，进一步探索chemerin 通过受体GPR1对高雄激素诱导的实验性类PCOS的调节机制。拟通过采用小鼠卵巢颗粒细胞、黄体细胞等体外培养模型和高雄激素诱导的PCOS在体模型，利用GPR1单抗、GPR1siRNA、chemerin 基因敲除小鼠、GPR1flox/flox 条件性敲除小鼠等工具，研究GPR1介导的信号通路在高雄激素诱导PCOS过程中的作用机制。并利用GPR1 siRNA/shRNA 等工具在体干预GPR1表达来调节PCOS模型的症状，以期为探寻脂肪因子与高雄激素诱导的PCOS的相关性及治疗靶点提供新的理论依据和坚实的实验基础。

Polycystic ovary syndrome is closely related to hyperandrogenism and obesity, but the mechanism has not been elucidated. Clinical data has shown that chemerin significantly is increased in the serum of patients with PCOS. We have the first report of chemerin, a novel adipokine, inhibiting testosterone secretion in both rat and mouse model. This project is planned on the basis of previous work, to further explore the regulatory mechanism chemerin /GPR1 signaling of PCOS induced by androgen. By using in vitro model, such as mouse ovarian granulosa cells, luteal cells culture, and androgen-induced in vivo PCOS model, by using GPR1 monoclonal antibody, GPR1siRNA, chemerin knockout mice, GPR1 flox / flox conditional knockout mice and other tools, we intend to research GPR1 mediated signal pathway in androgen-induced PCOS process mechanism. By using GPR1 siRNA / shRNA tools to intervene GPR1 expression in vivo model to adjust PCOS symptoms, we intend to seek the androgen-induced adipose factor correlation and therapeutic targets PCOS provide a new theoretical basis and solid experimental basis .