title: Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology.
abstract: Using cDNA cloning strategies commonly employed for G protein-coupled receptors (GPCR), GPCR-30 (GPR30), was isolated from mammalian cells before knowledge of its cognate ligand. GPR30 is evolutionarily conserved throughout the vertebrates. A broad literature suggests that GPR30 is a Gs-coupled heptahelical transmembrane receptor that promotes specific binding of naturally occurring and man-made estrogens but not cortisol, progesterone, or testosterone. Its "pregenomic" signaling actions are manifested by plasma membrane-associated actions familiar to GPCR, namely, stimulation of adenylyl cyclase and Gβγ-subunit protein-dependent release of membrane-tethered heparan bound epidermal growth factor. These facts regarding its mechanism of action have led to the formal renaming of this receptor to its current functional designate, G protein-coupled estrogen receptor (ER) (GPER)-1. Further insight regarding its biochemical action and physiological functions in vertebrates is derived from receptor knockdown studies and the use of selective agonists/antagonists that discriminate GPER-1 from the nuclear steroid hormone receptors, ERα and ERβ. GPER-1-selective agents have linked GPER-1 to physiological and pathological events regulated by estrogen action, including, but not limited to, the central nervous, immune, renal, reproductive, and cardiovascular systems. Moreover, immunohistochemical studies have shown a positive association between GPER-1 expression and progression of female reproductive cancer, a relationship that is diametrically opposed from ER. Unlike ER knockout mice, GPER-1 knockout mice are fertile and show no overt reproductive anomalies. However, they do exhibit thymic atrophy, impaired glucose tolerance, and altered bone growth. Here, we discuss the role of GPER-1 in female reproductive cancers as well as renal and vascular physiology.
authors.affiliation: Department of Medicine, Rhode Island Hospital and Brown University Medical School, 593 Eddy Street, Aldrich Building Room 708, Providence, Rhode Island 02903, USA. edward_filardo@brown.edu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Filardo
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001706:Biopsy; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005833:Genital Neoplasms, Female / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C109584:GPER1 protein, human; D008024:Ligands; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D066246:ErbB Receptors