Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, 50 Cheonghak-ri, Samrangjin-eup, Miryang, Gyeongsangnam-do, 627-706, South Korea.
Department of Obstetrics and Gynecology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University College of Medicine, Yangsan, Gyeongnam, 50612, South Korea.
Reprod Sci. 2020 Jul;27(7):1513-1521. doi: 10.1007/s43032-020-00142-5. Epub 2020 Jan 29.
The steroid hormones act by binding to their receptors and subsequently interacting with coactivators. Several classes of coactivators have been identified and shown to be essential in estradiol (E2) responsiveness. The major coregulators are the p160 steroid receptor coactivator (SRC) family. Although the function of SRCs in other organs has been well studied, it has not been thoroughly studied in the placenta. In addition, the correlation between preeclampsia (PE) and SRCs has not been examined previously. Therefore, we compared the expression patterns of SRCs in normal and PE placentas. In human PE placental tissues, SRC-1 mRNA, and protein levels were downregulated in the PE group. In addition, to assess the expression of SRCs in a PE environment, we used Reduced Uterine Perfusion Pressure (RUPP) model and placental cells were cultured in hypoxia condition. SRC-1 proteins were reduced in the placenta of PE-like rat RUPP model. Furthermore, SRCs proteins were significantly downregulated in hypoxia-grown placental cells. To examine the interaction between estrogen receptors (ERs) and SRC-1 protein, we performed co-immunoprecipitation. The interaction of SRC-1 with ERα was significantly stronger than that with ERβ. In PE placenta, the interaction of both ERα and ERβ with SRC-1 was stronger than that in normal placenta. In summary, our results demonstrate that expression levels of SRC-1, not SRC-2 and SRC-3, were decreased in hypoxia-induced PE placenta, which may further reduce the signaling of sex steroid hormones such as E2. The dysregulated signaling of E2 by SRC-1 expression could be associated with the PE placental symptoms of patients.
甾体激素通过与受体结合并随后与共激活剂相互作用来发挥作用。已经鉴定出几类共激活剂，并证明它们在雌二醇（E2）反应中是必不可少的。主要的共调节剂是 p160 甾体受体共激活剂（SRC）家族。尽管 SRC 在其他器官中的功能已得到充分研究，但在胎盘组织中尚未进行深入研究。此外，以前尚未检查过先兆子痫（PE）与 SRC 之间的相关性。因此，我们比较了正常和 PE 胎盘组织中 SRC 的表达模式。在人类 PE 胎盘组织中，PE 组中 SRC-1 mRNA 和蛋白水平下调。此外，为了评估 SRC 在 PE 环境中的表达，我们使用了减少子宫灌注压（RUPP）模型，并在缺氧条件下培养胎盘细胞。PE 样大鼠 RUPP 模型胎盘中的 SRC-1 蛋白减少。此外，缺氧培养的胎盘细胞中 SRCs 蛋白明显下调。为了检查雌激素受体（ERs）和 SRC-1 蛋白之间的相互作用，我们进行了共免疫沉淀。SRC-1 与 ERα 的相互作用明显强于与 ERβ 的相互作用。在 PE 胎盘组织中，ERα 和 ERβ 与 SRC-1 的相互作用均强于正常胎盘组织。总之，我们的结果表明，SRC-1 的表达水平而非 SRC-2 和 SRC-3 在缺氧诱导的 PE 胎盘中降低，这可能进一步降低了雌二醇等性激素的信号转导。SRC-1 表达对 E2 的失调信号可能与患者的 PE 胎盘症状有关。
