The DOI matches its Crossref record; 82 of the 83 references it cites were found in a registry or an index.
Minireview: G Protein-Coupled Estrogen Receptor-1, GPER-1: Its Mechanism of Action and Role in Female Reproductive Cancer, Renal and Vascular Physiology
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
2 retracted
Vivacqua, A., Bonofiglio, D., Albanito, L., Madeo, A., Rago, V., Carpino, A., Musti, A. M., Picard, D., Andò, S., & Maggiolini, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.026344 · Cited by 280
RetractedAlbanito, L., Lappano, R., Madeo, A., Chimento, A., Prossnitz, E. R., Cappello, A. R., Dolce, V., Abonante, S., Pezzi, V., & Maggiolini, M. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11297 · Cited by 105
RetractedCloning of a novel receptor expressed in rat prostate and ovary.
Kuiper, G. G. J. M., Enmark, E., Pelto‐Huikko, M., Nilsson, S., & Gustafsson, J.-Α. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5925 · Cited by 4,802
A transmembrane intracellular estrogen receptor mediates rapid cell signaling
Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B., & Prossnitz, E. R. (2005) · Science · doi:10.1126/science.1106943 · Cited by 2,302
Structural Basis of Integrin Regulation and Signaling
Luo, B., Carman, C. V., & Springer, T. A. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141618 · Cited by 1,662
Identity of an Estrogen Membrane Receptor Coupled to a G Protein in Human Breast Cancer Cells
Thomas, P., Pang, Y., Filardo, E. J., & Dong, J. (2004) · Endocrinology · doi:10.1210/en.2004-1064 · Cited by 1,410
Self-citationFilardo, E. J., Quinn, J. A., Bland, K. I., & Frackelton, A. R. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.10.0532 · Cited by 1,387
Self-citationThe G-protein-coupled estrogen receptor GPER in health and disease
Prossnitz, E. R., & Barton, M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.122 · Cited by 925 · cited 1×
“Excellent reviews have been written about the use of GPER-1-selective ligands, including the GPER-1 agonist G-1 and the GPER-1 antagonist G-15, to investigate disease models (8, 36).”
Blair, R. M. (2000) · Toxicological Sciences · doi:10.1093/toxsci/54.1.138 · Cited by 806
Seifert, R., & Wenzel‐Seifert, K. (2002) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-002-0588-0 · Cited by 657
Research works printed but not linked: 1
- 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
Cited by
Sorted by citations
Items 301–364 of 364
Approaches and methods to study cell signaling: Linguistics of cellular communication
Neog, S., & Trivedi, V. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90264-9.00036-2 · Cited by 2
Reichenbach, J., Fraungruber, P., Mayr, D. C., Buschmann, C., Kraus, F. B. T., Topalov, N. E., Chelariu-Raicu, A., Kolben, T., Burges, A., Mahner, S., et al. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-04708-z · Cited by 2
Schuller, H. M. (2018) · Translational Lung Cancer Research · doi:10.21037/tlcr.2018.03.04 · Cited by 2
Messersmith, E. M. (2021) · doi:10.31274/td-20240329-749 · Cited by 2
BENDARY, M. D. S. M. S. M. A., Amer, G., & RANA A. TAWFIK, M. S. (2019) · The Medical Journal of Cairo University/The Medical Journal of Cairo University · doi:10.21608/mjcu.2019.53563 · Cited by 1
Post-COVID-19 Neuropathology and Perspectives of Protective Roles of Estrogens
Ureshino, R. P., Stilhano, R. S., Prado, C. M., & Newson, L. R. (2025) · COVID · doi:10.3390/covid5010009 · Cited by 1
Desouza, J., Khan, R., Metkari, S., Singh, K., Narayanaswamy, S., Fernandes, G., Menon, S., Sable, N. P., Pal, M., Chaudhari, U. K., et al. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167740 · Cited by 1
Introduction to Hormonal Growth Promotants and Mechanism of Action
Smith, Z. K. F., & Johnson, B. J. (2026) · Veterinary Clinics of North America Food Animal Practice · doi:10.1016/j.cvfa.2025.12.002 · Cited by 1
Overexpression of GPER1 suppressed esophageal carcinoma growth via activating cAMP pathway
Yin, H., Han, X., Zhang, Q., Li, D., & Wang, F. (2026) · European Journal of Histochemistry · doi:10.4081/ejh.2026.4422 · Cited by 1
Gibbs, R. B. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190645908.003.0017 · Cited by 2
Proffitt, M. R., & Smith, G. T. (2024) · Hormones and Behavior · doi:10.1016/j.yhbeh.2024.105576 · Cited by 1
Novel aspects of the Renin-Angiotensin-Aldosterone System
Piazza, M. (2021) · doi:10.26481/dis.20211004mp · Cited by 1
Mogus, J. P., Marin, M., Arowolo, O. K., Salemme, V., & Suvorov, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.04.574224 · Cited by 1
Gonadectomia e DHEA: efeitos metabólicos em ratas adultas alimentadas com dieta hiperlipídica.
Teixeira, C. J. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2014.tde-11122014-111724
Ring, K. L. (2014) · Digital Commons-TMC (Texas Medical Center)
Arthritis and immune-mediated bone loss - role of estrogen signalling pathways
Engdahl, C. (2012) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Ervin, K. S. J. (2013) · The Atrium (University of Guelph)
The G Protein-Coupled Estrogen Receptor (GPER-1): A Novel Regulator in the Kidney
Liu, Z., Liu, N., & Cheng, S. (2015) · Nephrology - Open Journal · doi:10.17140/npoj-1-e002
Biological and therapeutic aspects of breast cancer progression
Karthik, G.-M. (2017) · Figshare
Equine Endometrial Development: Setting the Stage for Reproductive Success
Fraser, N. S. (2016)
Rodrigues, J. R. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2018.tde-19022018-135515
Cancer of Reproductive System: Receptors and Targeting Strategies
Gore, M., Puranik, A., Indurkar, A. R., Sonowal, B., Devarajan, P. V., Jain, R. D., & Dandekar, P. P. (2019) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-030-29168-6_4 · Cited by 1
Rapid Modulation of Spinogenesis by Estradiol in the Neocortex
Srivastava, D. P., Sellers, K. J., & Evans, P. D. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190645908.003.0005
The Research Advances in G-Protein-Coupled Estrogen Receptor
Zhang, H., Wang, Y., & Wang, B. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.105822
Marsh, C. A. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.100987
Wersäll, O. C., Razumova, Z., Govorov, I., & Mints, M. (2022) · Nutrition and Cancer · doi:10.1080/01635581.2022.2112241
GPER in molecular pharmacology and its therapeutic implications in breast cancer
Tan, M. (2024) · International Conference on Biological Engineering and Medical Science (ICBioMed) · doi:10.1117/12.3021712
Borlak, J. T., Ciribilli, Y., Bisio, A., Selvaraj, S., Inga, A., Oh, J., & Spanel, R. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4781335
Zhang, C., Wei, G., & Liu, L. (2024) · Research Square · doi:10.21203/rs.3.rs-4831686/v1
Ahmed, H. A., Shaaban, A. A., Ibrahim, T. M., & Makled, M. N. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2024.115079
The role of hormone receptors in breast cancer: New opportunities for treatment and prevention
Parvatikar, P., Ray, S. K., Kugaji, M. S., Sriram, A., & Singh, P. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33349-1.00013-2
Sun, Y., Leng, P., Guo, P., Gao, H., Liu, Y., Li, C., Li, Z., & Zhang, H. (2021) · Figshare · doi:10.6084/m9.figshare.16529988
ERα activates NAMPT/IL-33 signaling to enhance beige thermogenesis and metabolic fitness
Hu, R., Park, J., Qian, Y., Xiong, S., Elsabbagh, A. H., Chhikara, A., FAN, H., Shi, Z., Liu, L., Li, Y., et al. (2026) · Science Advances · doi:10.1126/sciadv.adz1385
Singh, R., Sharma, P., Agarwal, S., Modanwal, S., Paulraj, S., & Mahto, S. K. (2026) · Reproductive Toxicology · doi:10.1016/j.reprotox.2026.109211
Li, Y., & Jiao, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1764287
Développement d'analogues urotensinergiques radiomarqués pour l'imagerie de tumeurs solides
Poret, B. (2018) · theses.fr (ABES) · doi:10.70675/bbffea07z6c9cz43f4zb871z7b6df9df9cd2
Modalités de régulation d’ERα36 et leurs conséquences sur la physiopathologie de la glande mammaire
Thiébaut, C. (2019) · theses.fr (ABES) · doi:10.70675/a9ebb280zacf2z4fa3za947zeb7b888f9545
Cluzet, V. (2021) · theses.fr (ABES) · doi:10.70675/defdb8f3za64fz45c9z99d4zdbb95d4e9bb7
Lan, L., Zhang, X., Xie, J., Hong, X., Lin, X., & Mao, X. (2026) · Current Zoology · doi:10.1093/cz/zoag034
Estrogen receptor expression in GnRH neurons: back to the future
Oh, J., Li, H., Bunnell, M., Chan, A., Vasetska, A., Park, S., Stangenes, L., Lin, P.-C. P., Wang, K., & Ko, C. J. (2026) · Biology of Reproduction · doi:10.1093/biolre/ioag095
More than alternative estrogen receptors: the emerging role of GPER-1 and ERα36 in breast cancer
Molina, L., Torres, R. F., Spies, J., Meneses, S. S., Soto, M., Carrasco, J., Gálvez, J., Muñoz, D., Soto, J., & Arancibia, Y. (2026) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2026.1002377
Kurt, A. H., Çetintaş, V. B., Öztabağ, C. K., & Tosun, M. (2026) · Prospects in Pharmaceutical Sciences · doi:10.56782/pps.743
Estrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets
Licznerska, B. E., Szaefer, H., Sobierajska, H., & Baer‐Dubowska, W. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156823
Peschel, W. J., & Smith, Z. K. F. (2026) · Ruminants · doi:10.3390/ruminants6030073
Paredes, R., Donoso, M. V., Lagos, C. F., Cárdenas, C., Acuña‐Castillo, C., Valdés, D., Constandil, L., & Huidobro-Toro, J. P. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1891002
Female hormones enhance skin T cell expansion and suppress IFN-γ production
Bahri, R., Tontini, C., Kiss, O., Langton, A. K., Newton, V. L., Bell, M., & Bulfone‐Paus, S. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1903552
Steroid Hormone Receptors and Signal Transduction Processes
Klinge, C. M. (2026) · Endocrinology · doi:10.1007/978-3-319-27318-1_9-2
The neurobiology of menopause: Implications for brain aging and Alzheimer’s risk
Mosconi, L. (2026) · Neuron · doi:10.1016/j.neuron.2026.09.015
Lopes, D. C. F. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2014.tde-25112014-140744
Estrogen Dependent Regulation of the Amp-Activated Protein Kinase Pathway
Lipovka, Y. (2015) · UA Campus Repository (The University of Arizona)
Metadata
- 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 › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
