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REVIEW ARTICLE

G protein-coupled estrogen receptor 1 and its role in sex-specific differences in neurological and cardiovascular diseases

Oliver Dräger1 ,  Julia Gottschalk1 ,  Erhard Wischmeyer1 ,  Beatrice A. Nossek1*
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1 Department of Cellular Neurophysiology, Medical School OWL, Bielefeld University, Bielefeld, Germany
GPD, 4632 https://doi.org/10.36922/gpd.4632
Submitted: 22 August 2024 | Accepted: 22 October 2024 | Published: 22 November 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Estrogen receptors (ERs) and their ligands play a crucial role in physiological and pathophysiological processes, particularly in the central nervous and cardiovascular systems. There is increasing evidence that besides the two cytosolic and nuclear ERs, namely, ERα and ERβ, the seven-transmembrane G protein-coupled ER 1 (GPER1) is of great importance in the molecular mechanisms underlying various neurological and cardiovascular diseases and is probably responsible for sex-specific differences. In contrast to ERα and ERβ, GPER1 mediates its effects through not only transcriptional regulation but also rapid nongenomic signaling. This emphasizes the role of GPER1 in the modulation of acute pathophysiological mechanisms involving changes in diverse signaling pathways related to neurological and cardiological aspects. In this review, we have summarized the role of GPER1 in disorders of excitable tissues, including neuroinflammation, learning and memory, Alzheimer’s disease, Parkinson’s disease, depression and mood disorders, schizophrenia, epilepsy, autism spectrum disorders and attention-deficit/hyperactivity disorder, migraine and pain, cardiovascular hypertension, cardiovascular function and fibrosis, hypertrophy, and atrial fibrillation, with a special focus on its involvement in sex-specific differences. We have assessed reports investigating the role of GPER1 in rodents and humans using in vivo and in vitro data. We have also reviewed the role of nutraceuticals, especially phytoestrogens, in this context. Furthermore, we have discussed the potential of GPER1 as a target for novel therapeutic interventions and prognostic indicator of neurological and cardiovascular diseases with a focus on sex-specific differences.

Keywords
G protein-coupled estrogen receptor 1
Sex-specific differences
Neurological diseases
Cardiovascular diseases
Estrogen
Estrogen receptors
Funding
None.
Conflict of interest
The authors declare that they have no conflicts of interest.
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