Chapter 6 Caveolae and Estrogen Receptor Signaling

The hormone estrogen has both slow genomic actions and rapid nongenomic actions in a variety of cell types. Recent work indicates that the rapid responses are mediated by a subpopulation of plasma membrane-associated estrogen receptors (ERs). The mechanisms of action of plasma membrane-associated ERs have been elucidated in considerable detail in endothelial cells, in which estrogen causes rapid stimulation of nitric oxide (NO) production by endothelial NO synthase (eNOS) (Caulin-Glaser et al., 1997; Lantin-Hermoso et al., 1997; Chen et al., 1999). This chapter reviews studies that localized eNOS activation by estrogen to the plasma membrane of endothelial cells, and then addresses additional experiments that implicated a subpopulation of plasma membrane-associated ERα. The further localization of ERα-eNOS coupling to endothelial cell caveolae is then discussed, followed by a review of comparable localization and action of a subpopulation of caveolae-associated ERβ in endothelium. The role of G-proteins in ERα coupling to eNOS is also considered. Last, additional intricacies about the identity of ERs in caveolae are addressed. The cumulative observations that will be reviewed offer compelling evidence that caveolae provide a signaling module in which plasma membrane-initiated ER signaling is organized.