Abstract：
The placenta-secreted human chorionic gonadotropin (hCG) is a hormone that plays a critical role in inducing ovarian progesterone production, which is required for maintaining normal pregnancy. The bioavailability of hCG depends on the expression of the beta-subunit of hCG (hCG-β) which is encoded by the chorionic gonadotropin beta (CGB) gene. G protein-coupled estrogen receptor (GPER) is a membrane estrogen receptor involved in non-genomic estrogen signaling. Estradiol (E2) has been shown to stimulate hCG production. However, the role of the GPER in regulating CGB expression remains unknown. In the present study, our results revealed that treatment with G1 upregulated CGB expression in two human choriocarcinoma cell lines, BeWo and JEG-3, and primary human cytotrophoblast cells. In addition, G1 treatment activated the cAMP-response element binding protein (CREB). Using a pharmacological inhibitor and siRNA-mediated knockdown approach, we showed that the stimulatory effect of G1 on CGB expression is mediated by the protein kinase A (PKA)-CREB signaling pathway. This study increases the understanding of the role of GPER in the human placenta. In addition, our results provide important insights into the molecular mechanisms that mediate hCG expression, which may lead to the development of alternative therapeutic approaches for treating placental diseases.
摘要：
胎盘分泌的人绒毛膜促性腺激素（hCG）是一种在诱导卵巢孕酮产生中起关键作用的激素，这是维持正常妊娠所必需的。hCG的生物利用度取决于由绒毛膜促性腺激素β(CGB)基因编码的hCGβ-亚基(hCG-β)的表达。G蛋白偶联雌激素受体(GPER)是参与非基因组雌激素信号传导的膜雌激素受体。已显示雌二醇(E2)刺激hCG产生。然而,GPER在调节CGB表达中的作用尚不清楚.在本研究中,我们的结果表明，用G1治疗上调CGB在两个人绒毛膜癌细胞系的表达，BeWo和JEG-3，以及原代人细胞滋养层细胞。此外,G1处理激活了cAMP反应元件结合蛋白(CREB)。使用药理学抑制剂和siRNA介导的敲低方法，我们发现G1对CGB表达的刺激作用是由蛋白激酶A（PKA）-CREB信号通路介导的。这项研究增加了对GPER在人类胎盘中的作用的理解。此外,我们的结果为介导hCG表达的分子机制提供了重要的见解，这可能导致治疗胎盘疾病的替代治疗方法的发展。
