Emerging evidence of the importance of rapid, non-nuclear estrogen receptor signaling in the cardiovascular system

Estrogen receptors are classically known as ligand-activated transcription factors that regulate gene transcription in cells in response to hormone binding. In addition to this genomic signaling pathway, a rapid, non-nuclear signaling pathway mediated by cell membrane-associated estrogen receptors also has been recognized. Although for many years there was little evidence to support any physiological relevance of rapid-signaling, very recently evidence has been accumulating supporting the importance of the rapid, non-nuclear signaling as potentially critical for the protective effects of estrogen in the cardiovascular system. Better understanding of the rapid, non-nuclear signaling potentially provides an opportunity to design pathway-specific selective estrogen receptor modulators capable of differentially regulating non-nuclear vs. genomic effects that may prove useful ultimately as specific therapies for cardiovascular diseases. (C) 2012 Elsevier Inc. All rights reserved.