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Gene & Protein in Disease

REVIEW ARTICLE
G protein-coupled estrogen receptor 1 and its

role in sex-specific differences in neurological
and cardiovascular diseases

Oliver Dräger , Julia Gottschalk, Erhard Wischmeyer, and Beatrice A. Nossek*

Department of Cellular Neurophysiology, Medical School OWL, Bielefeld University, Bielefeld,
Germany

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.
*Corresponding author: In this review, we have summarized the role of GPER1 in disorders of excitable
Beatrice A. Nossek tissues, including neuroinflammation, learning and memory, Alzheimer’s disease,
(beatrice.nossek@uni-bielefeld.de)
Parkinson’s disease, depression and mood disorders, schizophrenia, epilepsy, autism
Citation: Dräger O, spectrum disorders and attention-deficit/hyperactivity disorder, migraine and pain,
Gottschalk J, Wischmeyer E,
Nossek BA. G protein-coupled cardiovascular hypertension, cardiovascular function and fibrosis, hypertrophy, and
estrogen receptor 1 and its role atrial fibrillation, with a special focus on its involvement in sex-specific differences. We
in sex-specific differences in have assessed reports investigating the role of GPER1 in rodents and humans using
neurological and cardiovascular in vivo and in vitro data. We have also reviewed the role of nutraceuticals, especially
diseases. Gene Protein Dis.
2025;4(1):4632. phytoestrogens, in this context. Furthermore, we have discussed the potential of
doi: 10.36922/gpd.4632 GPER1 as a target for novel therapeutic interventions and prognostic indicator of
Received: August 22, 2024 neurological and cardiovascular diseases with a focus on sex-specific differences.
1st revised: September 11, 2024
2nd revised: October 18, 2024
Accepted: October 22, 2024 Keywords: G protein-coupled estrogen receptor 1; Sex-specific differences; Neurological
Published online: November 22, diseases; Cardiovascular diseases; Estrogen; Estrogen receptors
2024
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
1
and reproduction in any medium, Sex-specific differences in diseases of the central nervous system (CNS) and
provided the original work is cardiovascular system are currently generally accepted, and the underlying molecular
2-6
properly cited. mechanisms have been widely investigated in the past few decades. As sex hormones
Publisher’s Note: AccScience play a key role in developmental and regulatory processes in physiological and
Publishing remains neutral with pathophysiological conditions in both males and females, they are prominent candidates
regard to jurisdictional claims in
published maps and institutional influencing the regulatory processes that result in sex differences. Together with the
affiliations. well-known intracellular estrogen receptor (ER) alpha (ERα) and ERβ, which regulate

Volume 4 Issue 1 (2025) 1 doi: 10.36922/gpd.4632