scholarly journals Minireview: G Protein-Coupled Estrogen Receptor-1, GPER-1: Its Mechanism of Action and Role in Female Reproductive Cancer, Renal and Vascular Physiology

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 2953-2962 ◽  
Author(s):  
Edward J. Filardo ◽  
Peter Thomas
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Mechanism Of Action ◽  
Knockout Mice ◽  
Mammalian Cells ◽  
Hormone Receptors ◽  
Bone Growth ◽  
Steroid Hormone Receptors ◽  
Vascular Physiology ◽  
G Protein Coupled

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.

scholarly journals G Protein-Coupled Estrogen Receptor 1 (GPER) as a Novel Target for Schizophrenia Drug Treatment

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Danielle S Macêdo ◽  
Lia Lira Olivier Sanders ◽  
Raimunda das Candeias ◽  
Cyntia de Freitas Montenegro ◽  
David Freitas de Lucena ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Brain Inflammation ◽  
Antipsychotic Treatment ◽  
New Class ◽  
Estrogen Receptor Modulators ◽  
Novel Target ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Abstract The observation that a person’s sex influences the onset age of schizophrenia, the course of the disease, and antipsychotic treatment response suggests a possible role for estrogen receptors in the pathophysiology of schizophrenia. Indeed, treatment with adjunctive estrogen or selective estrogen receptor modulators (SERMs) are known to reduce schizophrenia symptoms. While estrogen receptors (ER)α and ERβ have been studied, a third and more recently discovered estrogen receptor, the G protein-coupled estrogen receptor 1 (GPER), has been largely neglected. GPER is a membrane receptor that regulates non-genomic estrogen functions, such as the modulation of emotion and inflammatory response. This review discusses the possible role of GPER in brain impairments seen in schizophrenia and in its potential as a therapeutic target. We conducted a comprehensive literature search in the PubMed/MEDLINE database, using the following search terms: “Schizophrenia,” “Psychosis,” “GPER1 protein,” “Estrogen receptors,” “SERMS,” “GPER1 agonism, “Behavioral symptoms,” “Brain Inflammation.” Studies involving GPER in schizophrenia, whether preclinical or human studies, have been scarce, but the results are encouraging. Agonism of the GPER receptor could prove to be an essential mechanism of action for a new class of “anti-schizophrenia” drugs.

scholarly journals G Protein-Coupled Estrogen Receptor in Cancer and Stromal Cells: Functions and Novel Therapeutic Perspectives

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 672
Author(s):  
Richard A. Pepermans ◽  
Geetanjali Sharma ◽  
Eric R. Prossnitz
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Inflammatory Diseases ◽  
Therapy Resistance ◽  
Breast Cancers ◽  
Obesity And Diabetes ◽  
Therapeutic Value ◽  
Health And Disease ◽  
Multiple Cells ◽  
G Protein Coupled

Estrogen is involved in numerous physiological and pathophysiological systems. Its role in driving estrogen receptor-expressing breast cancers is well established, but it also has important roles in a number of other cancers, acting both on tumor cells directly as well as in the function of multiple cells of the tumor microenvironment, including fibroblasts, immune cells, and adipocytes, which can greatly impact carcinogenesis. One of its receptors, the G protein-coupled estrogen receptor (GPER), has gained much interest over the last decade in both health and disease. Increasing evidence shows that GPER contributes to clinically observed endocrine therapy resistance in breast cancer while also playing a complex role in a number of other cancers. Recent discoveries regarding the targeting of GPER in combination with immune checkpoint inhibition, particularly in melanoma, have led to the initiation of the first Phase I clinical trial for the GPER-selective agonist G-1. Furthermore, its functions in metabolism and corresponding pathophysiological states, such as obesity and diabetes, are becoming more evident and suggest additional therapeutic value in targeting GPER for both cancer and other diseases. Here, we highlight the roles of GPER in several cancers, as well as in metabolism and immune regulation, and discuss the therapeutic value of targeting this estrogen receptor as a potential treatment for cancer as well as contributing metabolic and inflammatory diseases and conditions.

Sign in / Sign up

Export Citation Format

Share Document