Department of Obstetrics and Gynaecology, University of Toyama, Toyama, 930-0194, Japan.
Department of Obstetrics and Gynaecology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0375, Japan.
Mol Cell Endocrinol. 2020 May 15;508:110792. doi: 10.1016/j.mce.2020.110792. Epub 2020 Mar 19.
Polycystic ovary syndrome (PCOS) is a clinical syndrome characterized by hyperandrogenism, oligo/anovulation, and polycystic ovary. Autophagy is an intracellular system that degrades cytosolic proteins and organelles. The relationship between autophagy and PCOS has not been clarified. We found that p62 and ubiquitin were significantly increased in theca cells of women with PCOS using immunohistochemistry. Autophagy inhibition by palmitic acid and chloroquine in bovine theca cells increased p62 and ubiquitin and induced the expression of cytochrome P450 17A1 (CYP17A1) and plasminogen activator inhibitor-1 (PAI-1) mRNA. Furthermore, palmitic acid and chloroquine exposure significantly increased reactive oxygen species (ROS) and activated p38 and c-Jun N-terminal kinase (JNK). Inhibition of p38 and JNK significantly reduced CYP17A1 and PAI-1 mRNA expression. We showed that inhibition of autophagy in theca cells may have contributed to the pathogenesis of PCOS, based on CYP17A1 and PAI-1 mRNA expression via the ROS/p38 and JNK signalling pathways.
多囊卵巢综合征（PCOS）是一种以高雄激素血症、卵巢排卵功能障碍或丧失以及多囊卵巢为特征的临床综合征。自噬是一种降解胞质蛋白和细胞器的细胞内系统。自噬与 PCOS 之间的关系尚未阐明。我们发现，使用免疫组织化学法，PCOS 患者的卵巢间质细胞中 p62 和泛素明显增加。脂肪酸和氯喹抑制牛卵巢间质细胞中的自噬会增加 p62 和泛素，并诱导细胞色素 P450 17A1（CYP17A1）和纤溶酶原激活物抑制剂-1（PAI-1）mRNA 的表达。此外，脂肪酸和氯喹暴露会显著增加活性氧（ROS）并激活 p38 和 c-Jun N 端激酶（JNK）。抑制 p38 和 JNK 可显著降低 CYP17A1 和 PAI-1 mRNA 的表达。我们表明，通过 ROS/p38 和 JNK 信号通路，抑制卵巢间质细胞中的自噬可能导致 PCOS 的发病机制，导致 CYP17A1 和 PAI-1 mRNA 的表达。
