Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function

Milad Rouhimoghadam; Anh S Lu; Aliasger K Salem; Edward J Filardo

doi:10.3389/fendo.2020.591217

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Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function

Journal article

Open access

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Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function

Milad Rouhimoghadam, Anh S Lu, Aliasger K Salem and Edward J Filardo

Frontiers in endocrinology (Lausanne), Vol.11, pp.591217-591217

11/23/2020

DOI: 10.3389/fendo.2020.591217

PMCID: PMC7719807

PMID: 33329395

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Abstract

Estrogens exert their physiological and pathophysiological effects via cellular receptors, named ERα, ERβ, and G-protein coupled estrogen receptor (GPER). Estrogen-regulated physiology is tightly controlled by factors that regulate estrogen bioavailability and receptor sensitivity, while disruption of these control mechanisms can result in loss of reproductive function, cancer, cardiovascular and neurodegenerative disease, obesity, insulin resistance, endometriosis, and systemic lupus erythematosus. Restoration of estrogen physiology by modulating estrogen bioavailability or receptor activity is an effective approach for treating these pathological conditions. Therapeutic interventions that block estrogen action are employed effectively for the treatment of breast and prostate cancer as well as for precocious puberty and anovulatory infertility. Theoretically, treatments that block estrogen biosynthesis should prevent estrogen action at ERs and GPER, although drug resistance and ligand-independent receptor activation may still occur. In addition, blockade of estrogen biosynthesis does not prevent activation of estrogen receptors by naturally occurring or man-made exogenous estrogens. A more complicated scenario is provided by anti-estrogen drugs that antagonize ERs since these drugs function as GPER agonists. Based upon its association with metabolic dysregulation and advanced cancer, GPER represents a therapeutic target with promise for the treatment of several critical health concerns facing Western society. Selective ligands that specifically target GPER have been developed and may soon serve as pharmacological agents for treating human disease. Here, we review current forms of estrogen therapy and the implications that GPER holds for these therapies. We also discuss existing GPER targeted drugs, additional approaches towards developing GPER-targeted therapies and how these therapies may complement existing modalities of estrogen-targeted therapy.

anti-estrogens

therapeutics

cancer

estrogen receptors

Endocrinology

GPER

Details

Title: Subtitle: Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function
Creators: Milad Rouhimoghadam - Department of Surgery, University of Iowa, Carver College of Medicine
Anh S Lu - College of Pharmacy, University of Iowa
Aliasger K Salem - Holden Comprehensive Cancer Center, University of Iowa
Edward J Filardo - Department of Surgery, University of Iowa, Carver College of Medicine
Resource Type: Journal article
Publication Details: Frontiers in endocrinology (Lausanne), Vol.11, pp.591217-591217
DOI: 10.3389/fendo.2020.591217
PMID: 33329395
PMCID: PMC7719807
NLM abbreviation: Front Endocrinol (Lausanne)
ISSN: 1664-2392
eISSN: 1664-2392
Publisher: Frontiers Media S.A
Grant note: Roy J. and Lucille A. Carver College of Medicine, University of Iowa
Language: English
Date published: 11/23/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Internal Medicine
Record Identifier: 9984066350002771

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