GnRH agonist reduces estrogen receptor dimerization in GT1-7 cells: Evidence for cross-talk between membrane-initiated estrogen and GnRH signaling

17 beta-estradiol (E-2), 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 (ER alpha) and beta (ER beta) and gonadotropin releasing hormone receptor (GnRH-R) in GT1-7 cells. Radioligand binding studies demonstrated a significant decrease in saturation E-2 binding in cells treated with GnRH agonist. Conversely, there was a significant reduction in GnRH binding in GT1-7 cells treated with E-2. In BRET1 experiments, ER alpha-ER alpha 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 ERa homodimerization by GnRH agonist. Collectively, these findings demonstrate significant cross-talk between membrane-initiated GnRH and E-2 signaling in GT1-7 cells. Published by Elsevier Ireland Ltd.