title: GnRH agonist reduces estrogen receptor dimerization in GT1-7 cells: evidence for cross-talk between membrane-initiated estrogen and GnRH signaling.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Chason
authors.affiliation: 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.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, University of Miami, 1611 NW 12th Ave, Miami, FL 33136, USA.
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Gerkowicz
authors.affiliation: 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.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Dufau
authors.affiliation: Endocrinology and Reproduction Research Branch, Section on Hormonal Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Catt
authors.affiliation: 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. Electronic address: segarsj@mail.nih.gov.
authors.forename: James H
authors.initials: JH
authors.lastname: Segars
mesh_terms: D001665:Binding Sites; D060807:Bioluminescence Resonance Energy Transfer Techniques; D002460:Cell Line; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000737:chemistry* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D055503:Protein Multimerization / Q000187:drug effects; D011869:Radioligand Assay; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol
keywords: Estradiol; Estrogen receptor alpha; Estrogen receptor beta; GT1-7 cells; GnRH receptor; Non-classical estrogen signaling