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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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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Estrogen transmits signals via GPERs to transactivate epidermal growth factor receptors for cell proliferation in female reproductive cancers.
“Estrogen transmits signals via GPERs to transactivate epidermal growth factor receptors for cell proliferation in female reproductive cancers [26].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [26]
GPER1-mediated nongenomic activity is independent of the estrogen nuclear receptor.
“GPER1-mediated nongenomic activity is independent of the estrogen nuclear receptor [26].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [26]
GPR30 has shown negligible binding to estrogen (17β-estradiol) in several studies.
“GPR30 has shown negligible binding to estrogen (17β-estradiol) in several studies [49], which may be due to the different analytical methods [17].”
From G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane (2014) · cites this paper as [17]
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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.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-04-11
- Volume
- 153
- Issue
- 7
- Pages
- 2953-2962
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- 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 › Genetics › 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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