Cited by 231Estrogen and related hormone effectsReceptor Mechanisms and SignalingEffects and risks of endocrine disrupting chemicals

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The G protein-coupled oestrogen receptor GPER in health and disease: an update

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Prossnitz, Eric R., Barton, Matthias·2023·Nature Reviews Endocrinology

DOI 10.1038/s41574-023-00822-7PMC PMC10187525

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Abstract

Oestrogens and their receptors contribute broadly to physiology and diseases. In premenopausal women, endogenous oestrogens protect against cardiovascular, metabolic and neurological diseases and are involved in hormone-sensitive cancers such as breast cancer. Oestrogens and oestrogen mimetics mediate their effects via the cytosolic and nuclear receptors oestrogen receptor-α (ERα) and oestrogen receptor-β (ERβ) and membrane subpopulations as well as the 7-transmembrane G protein-coupled oestrogen receptor (GPER). GPER, which dates back more than 450 million years in evolution, mediates both rapid signalling and transcriptional regulation. Oestrogen mimetics (such as phytooestrogens and xenooestrogens including endocrine disruptors) and licensed drugs such as selective oestrogen receptor modulators (SERMs) and downregulators (SERDs) also modulate oestrogen receptor activity in both health and disease. Following up on our previous Review of 2011, we herein summarize the progress made in the field of GPER research over the past decade. We will review molecular, cellular and pharmacological aspects of GPER signalling and function, its contribution to physiology, health and disease, and the potential of GPER to serve as a therapeutic target and prognostic indicator of numerous diseases. We also discuss the first clinical trial evaluating a GPER-selective drug and the opportunity of repurposing licensed drugs for the targeting of GPER in clinical medicine.

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Authors: Prossnitz, E. R., & Barton, M.
Affiliations: University of New Mexico (US)
University of Zurich (CH)
Corresponding author: Prossnitz, Eric R.
Barton, Matthias
ORCID: Prossnitz, Eric R.
Barton, Matthias
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2023-05-16
Volume: 19
Issue: 7
Pages: 407-424
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/s41574-023-00822-7
PMC: PMC10187525
OpenAlex: W4376639723
Cited by: 231
References: 292
Citations by year: 2026: 63 · 2025: 91 · 2024: 68 · 2023: 9
FWCI: 8.91
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
Dialysis Clinics
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (122504, 108258)
National Institutes of Health (CA118100, CA163890, GM121176)
National Cancer Institute (R01CA127731, R01CA163890, P30CA118100, R01CA194496)
National Institute of General Medical Sciences (P20GM121176)
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: endocrine disruptors, selective estrogen receptor modulators, estrogen receptor alpha, estrogen receptor beta, therapeutic target, drug repurposing
MeSH terms: Breast Neoplasms, Estrogens, Female, Humans, Receptors, Estrogen, GTP-Binding Proteins, Receptors, G-Protein-Coupled, Estrogen Receptor alpha, Estrogen Receptor beta

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The G protein-coupled oestrogen receptor GPER in health and disease: an update

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