Rapid vascular cell responses to estrogen and membrane receptors

There is a growing interest in the effects of estrogen on the vascular wall, due to the marked gender difference in the incidence of clinically apparent coronary heart disease, when comparing premenopausal women with age-matched males. Estrogen has numerous effects on vascular endothelial and smooth muscle cells, both of which express estrogen receptors (ERs). Although ERs are classically defined as ligand-activated transcription factors, it has become increasingly clear that estrogen-stimulated, ER-dependent cellular responses can be rapid consequences of signal transduction cascades. The cellular localization and molecular form of the ER(s) which mediates rapid signaling are poorly defined. In this review, we describe the mounting evidence for membrane-localized ERs that vary in structure from classical forms. We also discuss ER-catalyzed molecular complex formations and a variety of estrogen-triggered signal transduction cascades, including those involving phosphatidylinositol 3-kinase/Akt, MAP kinase and G-protein-coupled receptors, all of which may induce “protective” profiles in vascular cells.