GPER: a novel target for non-genomic estrogen action in the cardiovascular system

Pharmacol Res. 2013 May;71:53-60. doi: 10.1016/j.phrs.2013.02.008. Epub 2013 Mar 4.

Abstract

A key to harnessing the enormous therapeutic potential of estrogens is understanding the diversity of estrogen receptors and their signaling mechanisms. In addition to the classic nuclear estrogen receptors (i.e., ERα and ERβ), over the past decade a novel G-protein-coupled estrogen receptor (GPER) has been discovered in cancer and other cell types. More recently, this non-genomic signaling mechanism has been found in blood vessels, and mediates vasodilatory responses to estrogen and estrogen-like agents; however, downstream signaling events involved acute estrogen action remain unclear. The purpose of this review is to discuss the latest knowledge concerning GPER modulation of cardiovascular function, with a particular emphasis upon how activation of this receptor could mediate acute estrogen effects in the heart and blood vessels (i.e., vascular tone, cell growth and differentiation, apoptosis, endothelial function, myocardial protection). Understanding the role of GPER in estrogen signaling may help resolve some of the controversies associated with estrogen and cardiovascular function. Moreover, a more thorough understanding of GPER function could also open significant opportunities for the development of new pharmacological strategies that would provide the cardiovascular benefits of estrogen while limiting the potentially dangerous side effects.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System / cytology
  • Cardiovascular System / metabolism*
  • Cell Proliferation
  • Cyclic AMP / metabolism
  • Estrogens / metabolism*
  • Humans
  • MAP Kinase Signaling System
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / metabolism*
  • Receptors, G-Protein-Coupled / analysis
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Estrogens
  • GPER1 protein, human
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Cyclic AMP