Membrane-initiated actions of estrogen on the endothelium.
Estrogen-induced rapid, membrane-initiated activation of numerous signal transduction cascades has been shown in animal, cellular and molecular vascular studies, which support the favorable effects of estrogen on vascular structure and function. These effects are mediated by distinct forms of estrogen receptor (ER) alpha. This includes estrogen-stimulated, rapid activation of endothelial nitric oxide synthase (eNOS), resulting in elaboration of the athero-protective, angiogenesis-promoting product nitric oxide (NO). An N-terminus truncated short isoform of ERalpha, ER46, plays a critical role in membrane-initiated, rapid responses to 17beta-estradiol (E2) in human endothelial cells (ECs). We have proposed a ER46-centered, eNOS-activating molecular complex in human EC caveolar membranes, containing c-Src, phosphatidylinositol 3-kinase (PI3K), Akt and eNOS. In this review, we describe estrogen-induced, rapid, non-genomic actions in the endothelium.
Kim
Kyung Hee
KH
Division of Cardiovascular Medicine and Departments of Internal Medicine, Immunobiology and the Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, New Haven, CT 06520, USA.
Bender
Jeffrey R
JR
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D052250:Nitric Oxide Synthase Type III