Chason Rebecca J, Kang Jung-Hoon, Gerkowicz Sabrina A, Dufau Maria L, Catt Kevin J, Segars James H
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 CRC, Room 1E-3140, 10 Center Drive, MSC 1109, Bethesda, MD 20892-1109, USA.
Section on Molecular Endocrinology, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
Mol Cell Endocrinol. 2015 Mar 15;404:67-74. doi: 10.1016/j.mce.2015.01.023. Epub 2015 Jan 22.
17β-estradiol (E2), a key participant on the initiation of the LH surge, exerts both positive and negative feedback on GnRH neurons. We sought to investigate potential interactions between estrogen receptors alpha (ERα) and beta (ERβ) and gonadotropin releasing hormone receptor (GnRH-R) in GT1-7 cells. Radioligand binding studies demonstrated a significant decrease in saturation E2 binding in cells treated with GnRH agonist. Conversely, there was a significant reduction in GnRH binding in GT1-7 cells treated with E2. In BRET(1) experiments, ERα-ERα dimerization was suppressed in GT1-7 cells treated with GnRH agonist (p < 0.05). There was no evidence of direct interaction between ERs and GnRH-R. This study provides the first evidence of reduced ERα homodimerization by GnRH agonist. Collectively, these findings demonstrate significant cross-talk between membrane-initiated GnRH and E2 signaling in GT1-7 cells.
17β-雌二醇（E2）是促黄体生成素峰启动的关键参与者，对促性腺激素释放激素（GnRH）神经元具有正负反馈作用。我们试图研究雌激素受体α（ERα）和β（ERβ）与GT1-7细胞中促性腺激素释放激素受体（GnRH-R）之间的潜在相互作用。放射性配体结合研究表明，用GnRH激动剂处理的细胞中饱和E2结合显著减少。相反，用E2处理的GT1-7细胞中GnRH结合显著减少。在生物发光共振能量转移（BRET(1)）实验中，用GnRH激动剂处理的GT1-7细胞中ERα-ERα二聚化受到抑制（p < 0.05）。没有证据表明ERs与GnRH-R之间存在直接相互作用。本研究首次提供了GnRH激动剂降低ERα同二聚化的证据。总体而言，这些发现表明GT1-7细胞中膜启动的GnRH与E2信号之间存在显著的相互作用。
