Center for Reproductive MedicineRen Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghai, China.
Reproduction. 2018 Jun;155(6):505-514. doi: 10.1530/REP-18-0015. Epub 2018 Apr 6.
Polycystic ovary syndrome, a common condition characterized by endocrine dysfunction, menstrual irregularity, anovulation and polycystic ovaries, affects 5-7% of reproductive-age women. , which is identified by a genome-wide association study as a risk locus for this syndrome, encodes a small GTPase involved in control of receptor internalization and early endosome fusion. We found that mRNA levels in luteinized granulosa cells of obese patients with polycystic ovary syndrome were lower than in those of obese women without the syndrome. RAB5A regulated follicle-stimulating hormone (FSH)-mediated translocation of the FSH receptor (FSHR) from the membrane to the cytoplasm and the subsequent FSH-FSHR signaling pathway. We showed that RAB5A negatively regulated aromatase expression and estradiol synthesis in human granulosa cells in association with changes in FSHR levels by way of the cAMP/PKA/CREB pathway. The regulation of FSHR by RAB5A may have been associated with two transcription factors, USF1 and USF2. In conclusion, gene was abnormally expressed in luteinized granulosa cells of obese patients with polycystic ovary syndrome, which may help explain high FSHR levels found in this syndrome.
多囊卵巢综合征是一种常见的内分泌功能障碍性疾病，其特征为月经不规律、无排卵和多囊卵巢，影响着 5-7%的育龄妇女。一项全基因组关联研究表明，该综合征的风险基因座为 ，它编码一种参与控制受体内化和早期内体融合的小 GTPase。我们发现，多囊卵巢综合征肥胖患者的黄体化颗粒细胞中 mRNA 水平低于非综合征肥胖患者。RAB5A 调节卵泡刺激素（FSH）介导的 FSH 受体（FSHR）从膜到细胞质的易位，以及随后的 FSH-FSHR 信号通路。我们表明，RAB5A 通过 cAMP/PKA/CREB 通路负调控人颗粒细胞中的芳香化酶表达和雌二醇合成，与 FSHR 水平的变化有关。RAB5A 对 FSHR 的调节可能与两个转录因子 USF1 和 USF2 有关。总之，多囊卵巢综合征肥胖患者的黄体化颗粒细胞中 基因异常表达，这可能有助于解释该综合征中发现的高 FSHR 水平。
