Journal article
Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology
Endocrinology (Philadelphia), Vol.153(7), pp.2953-2962
07/2012
DOI: 10.1210/en.2012-1061
PMCID: PMC3380306
PMID: 22495674
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.
Details
- Title: Subtitle
- Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology
- Creators
- Edward J Filardo - 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.eduPeter Thomas
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.153(7), pp.2953-2962
- Publisher
- United States
- DOI
- 10.1210/en.2012-1061
- PMID
- 22495674
- PMCID
- PMC3380306
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Grant note
- R01 CA119165 / NCI NIH HHS
- Language
- English
- Date published
- 07/2012
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Internal Medicine
- Record Identifier
- 9984051773802771
Metrics
11 Record Views