Emerging roles of GPER in diabetes and atherosclerosis

Abstract

G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor implicated in rapid estrogen signaling. Originally cloned from vascular endothelial cells, GPER plays a central role in the regulation of vascular tone and cell growth, as well as lipid and glucose homeostasis. This review highlights our knowledge of the physiological and pathophysiological functions of GPER in the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent findings of its roles in obesity, diabetes, and atherosclerosis, including the GPER-dependent regulation of lipid metabolism and inflammation, are presented. The therapeutic potential of targeting GPER-dependent pathways in chronic diseases such as coronary artery disease and diabetes and in the context of menopause is also discussed.

The G-protein coupled estrogen receptor, GPER: The inside and inside-out story

“…More in-depth, expert reviews detailing this work and future directions have been published Barton et al, 2013;Han and White, 2013;Barton and Prossnitz, 2015]. Here, highlights of this work are selected for the purpose of assisting the reader of this review to better identify common biological themes that are relevant to the action of this newly appreciated estrogen receptor.…”

International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators

“…However, as described above, estrogens, as well as other steroids, had also been demonstrated to mediate rapid cellular and physiologic responses, inconsistent with the time frame of transcriptional mechanisms (Falkenstein et al, 2000). The discovery and characterization of a third estrogen receptor in the 2000s (Filardo et al, 2000;Revankar et al, 2005;Thomas et al, 2005), namely GPR30/GPER, belonging to the family of 7-transmembrane G proteincoupled receptors (GPCRs), which classically mediate rapid responses such as kinase activation and ion mobilization, have expanded our understanding of the varied and complex activities of estrogenic compounds throughout the body (Prossnitz, , 2012Prossnitz and Barton, 2009, 2014Prossnitz and Maggiolini, 2009b;Filardo and Thomas, 2012;Han et al, 2013;Srivastava and Evans, 2013;Lappano et al, 2014;Barton and Prossnitz, 2015).…”

Effects of Bisphenol A on ion channels: Experimental evidence and molecular mechanisms

“…This hormone plays an important role in the physiology of a variety of tissues including the brain, the reproductive and the cardiovascular system, directly modulating the function of many cells through activation of steroid receptive molecules, mainly the estrogen receptors α and β. In addition, some cells also express the G-protein coupled receptor for 17β-estradiol, named GPR30 or GPER (G-protein coupled estrogen receptor) [14,15].…”