Cited by 366Estrogen and related hormone effectsReceptor Mechanisms and SignalingEffects and risks of endocrine disrupting chemicals

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Minireview: G Protein-Coupled Estrogen Receptor-1, GPER-1: Its Mechanism of Action and Role in Female Reproductive Cancer, Renal and Vascular Physiology

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Filardo, Edward J., Thomas, Peter·2012·Endocrinology

DOI 10.1210/en.2012-1061PMC PMC3380306

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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.

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2 retracted

RETRACTED: 17β-Estradiol, Genistein, and 4-Hydroxytamoxifen Induce the Proliferation of Thyroid Cancer Cells through the G Protein-Coupled Receptor GPR30
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Retracted
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Cornea-Hébert (1999) · doi:10.1002/(sici)1096-9861(19990628)409:2

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Filardo, 2007, Activation of the novel estrogen receptor G protein coupled receptor 30 (GPR30) at the plasma membrane., Endocrinology, 148, 3236, 10.1210/en.2006-1605 · DOI

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Authors: Filardo, E. J., & Thomas, P.
Affiliations: Brown University (US)
University of Texas at Austin Marine Science Institute (US)
Corresponding author: Filardo, Edward J.
ORCID: Filardo, Edward J.
Thomas, Peter
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2012-04-11
Volume: 153
Issue: 7
Pages: 2953-2962
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2012-1061
PMC: PMC3380306
OpenAlex: W2137207319
Cited by: 366
References: 83
Citations by year: 2026: 16 · 2025: 10 · 2024: 24 · 2023: 16 · 2022: 18 · 2021: 28 · 2020: 31 · 2019: 30 · 2018: 29 · 2017: 26 · 2016: 28 · 2015: 36 · 2014: 36 · 2013: 29 · 2012: 9
FWCI: 4.34
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Endocrinology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA119165)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords: G protein-coupled estrogen receptor, GPR30, estrogen signaling, female reproductive cancers, renal physiology, vascular physiology, adenylate cyclase, Gβγ subunits, estrogen receptor knockout mice, thymic atrophy, glucose tolerance, bone growth
MeSH terms: Animals, Biopsy, Female, Genital Neoplasms, Female, Humans, Kidney, Ligands, Models, Biological, Models, Genetic, Receptors, Estrogen, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Receptors, G-Protein-Coupled, Mice, ErbB Receptors

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Minireview: G Protein-Coupled Estrogen Receptor-1, GPER-1: Its Mechanism of Action and Role in Female Reproductive Cancer, Renal and Vascular Physiology

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