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1559181 
Journal Article 
Estrogen Signaling and Cardiovascular Disease 
Murphy, E 
2011 
Yes 
Circulation Research
ISSN: 0009-7330
EISSN: 1524-4571 
109 
6 
687-696 
21885836 
WOS:000294477200014 
Estrogen has pleiotropic effects on the cardiovascular
system. The mechanisms by which estrogen confers these pleiotropic effects are undergoing active
investigation. Until a decade ago, all estrogen signaling was thought to occur by estrogen
binding to nuclear estrogen receptors (estrogen receptor-alpha and estrogen receptor-beta), which
bind to DNA and function as ligand-activated transcription factors. Estrogen binding to the
receptor alters gene expression, thereby altering cell function. Estrogen also binds to nuclear
estrogen receptors that are tethered to the plasma membrane, resulting in acute activation of
signaling kinases such as PI3K. An orphan G-protein-coupled receptor, G-protein-coupled receptor
30, can also bind estrogen and activate acute signaling pathways. Thus, estrogen can alter cell
function by binding to different estrogen receptors. This article reviews the different estrogen
receptors and their signaling mechanisms, discusses mechanisms that regulate estrogen receptor
levels and locations, and considers the cardiovascular effects of estrogen signaling. (Circ Res.
2011;109:687-696.) 
estrogen; hormone replacement therapy; ischemia-reperfusion; nitric oxide