Yang Sizhu, Jia Yuanyuan, Wu Ze, Fu Bingxin, Zhou Shenghui, Pires Leticia Vicosa, Cheng Jung-Chien, Fang Lanlan
Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Gynaecology and Obstetrics, Federal University of Health Sciences of Porto Alegre, Rio Grande do Sul, Brazil.
Mol Cell Endocrinol. 2023 Nov 1;577:112033. doi: 10.1016/j.mce.2023.112033. Epub 2023 Jul 26.
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.
胎盘分泌的人绒毛膜促性腺激素（hCG）是一种在诱导卵巢产生孕酮过程中起关键作用的激素，而孕酮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）是一种参与非基因组雌激素信号传导的膜雌激素受体。已证明雌二醇（E2）可刺激hCG的产生。然而，GPER在调节CGB表达中的作用仍不清楚。在本研究中，我们的结果显示，用G1处理可上调两种人绒毛膜癌细胞系BeWo和JEG-3以及原代人细胞滋养层细胞中的CGB表达。此外，G1处理激活了环磷酸腺苷反应元件结合蛋白（CREB）。使用药理学抑制剂和小干扰RNA介导的敲低方法，我们表明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。本研究增进了对GPER在人胎盘中作用的理解。此外，我们的结果为介导hCG表达的分子机制提供了重要见解，这可能会导致开发治疗胎盘疾病的替代治疗方法。
