TY - JOUR
T1 - Novel role of estrogen receptors in vascular endothelium
AU - Shaul, Philip W.
N1 - Funding Information:
From the Department of Pediatrics, University of Texas Southwestern Medical Center" at Dallas, Dallas, TX. Supported by National Institutes of Health (NIH) grants Nos. HL58888, HL53546, and HD30276, an Established Investigator-ship of the American Heart Association and the Lowe Foundation. Address reprint requests to Philip W. Shaul, MD, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9063; e-maih PSHA UL @MEDN ET. SWMED.ED U Copyright 9 2000 by W.B. Saunders Company O146-0005/00/2401-0017510. 00/0
PY - 2000
Y1 - 2000
N2 - Estrogen has a variety of effects on the vascular wall including rapid vasodilation due to the stimulation of endothelial nitric oxide synthase (eNOS). Studies in cultured endothelium indicate that the hormone cause acute, direct activation of eNOS that is unaffected by actinomycin D but fully inhibited by estrogen receptor (ER) antagonism. Overexpression of ERα leads to marked enhancement of the acute response to estrogen, and this process is blocked by ER antagonism and requires the ERα hormone binding domain. The acute response of eNOS to estrogen can also be reconstituted in COS-7 cells cotransfected with ERα and eNOS, but not by transfection with eNOS alone. The inhibition of calcium influx, or tyrosine kinases or mitogen- activated protein (MAP) kinase prevents eNOS stimulation by estrogen, and estrogen causes rapid ER-dependent activation of MAP kinase. Thus, the acute effect of estrogen on eNOS is mediated by ERα functioning in a novel, nongenomic manner to activate the enzyme via calcium-dependent, MAP kinase- dependent mechanisms. Copyright (C) 2000 by W.B. Saunders Company.
AB - Estrogen has a variety of effects on the vascular wall including rapid vasodilation due to the stimulation of endothelial nitric oxide synthase (eNOS). Studies in cultured endothelium indicate that the hormone cause acute, direct activation of eNOS that is unaffected by actinomycin D but fully inhibited by estrogen receptor (ER) antagonism. Overexpression of ERα leads to marked enhancement of the acute response to estrogen, and this process is blocked by ER antagonism and requires the ERα hormone binding domain. The acute response of eNOS to estrogen can also be reconstituted in COS-7 cells cotransfected with ERα and eNOS, but not by transfection with eNOS alone. The inhibition of calcium influx, or tyrosine kinases or mitogen- activated protein (MAP) kinase prevents eNOS stimulation by estrogen, and estrogen causes rapid ER-dependent activation of MAP kinase. Thus, the acute effect of estrogen on eNOS is mediated by ERα functioning in a novel, nongenomic manner to activate the enzyme via calcium-dependent, MAP kinase- dependent mechanisms. Copyright (C) 2000 by W.B. Saunders Company.
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U2 - 10.1016/S0146-0005(00)80060-9
DO - 10.1016/S0146-0005(00)80060-9
M3 - Article
C2 - 10709864
AN - SCOPUS:0034090639
SN - 0146-0005
VL - 24
SP - 70
EP - 74
JO - Seminars in Perinatology
JF - Seminars in Perinatology
IS - 1
ER -