卵泡刺激素通过ERK1/2信号通路调控卵巢上皮性细胞的自噬

Our previous studies have revealed that follicle-stimulating hormone (FSH) could change the autophagic level in ovarian epithelial cells. We also found in the preliminary experiments that activation of ERK1/2 signaling pathway could increase the formation of autophagosome in ovarian epithelial cells. Accordingly, we hypothesise that FSH could regulate the autophagic flux through ERK1/2 pathway in ovarian epithelial cells. To verify the hypothesis, we plan to (1) confirm the effects of FSH treatment on autophagy in ovarian epithelial cells by detecting the change in autophagic flux and expression of the autophagic proteins, (2) analysis the activation and subcellular location of ERK1/2 by FSH treatment, and investigate the role of ERK1/2 pathway involved in the autophgy regulation by using inhibitors of related signaling pathway, (3) and test the impact of FSH on the viability of ovarian epithelial cells in vitro and in vivo. The result of our study will provide new evidences and clues for the biologic mechanism of FSH, which may be helpful to better understanding of the pathogenesis of ovarian epithelial disease.

我们的前期研究发现：卵泡刺激素（FSH）可以改变卵巢上皮性细胞的自噬水平；ERK1/2信号通路的活化可以增加卵巢上皮性细胞内自噬体的数量。本课题提出以下假设：FSH通过ERK1/2信号通路调控卵巢上皮性细胞的自噬，并拟从以下三个方面开展研究：（1）通过检测细胞内自噬流变化、自噬相关蛋白表达水平改变，验证FSH对卵巢上皮性细胞自噬的调控作用；（2）检测FSH对ERK1/2活性及亚细胞定位的影响，并通过抑制剂阻断信号通路的激活，研究ERK1/2信号通路在FSH调控细胞自噬中的作用，及其与AMPK、mTOR通路之间的关系；（3）通过体内、外实验，研究FSH调控自噬对卵巢上皮性细胞生存能力的影响。通过本课题的研究可为FSH生物学功能的作用机制研究拓展思路，有利于研究FSH相关的卵巢上皮性病变的发病机制。