Stereoisomer-specific inhibition of superoxide anion-induced rat aortic smooth-muscle cell proliferation by 17beta-estradiol is estrogen receptor dependent.
An in vitro xanthine/xanthine oxidase reaction system was used to generate superoxide anions that significantly stimulated tritiated [3H]thymidine incorporation into endothelium-removed (denuded) male rat aortic explants. Tritiated thymidine uptake was used as an index of vascular smooth-muscle cell (VSMC) proliferation. Superoxide dismutase (SOD) significantly attenuated the oxygen free radical-induced proliferative response of these cells. 17Beta-estradiol (17beta-E) significantly inhibited superoxide anion-induced VSMC proliferation. In contrast, the growth-modifying effects of 17beta-E were not mimicked by 17alpha-estradiol (17alpha-E), progesterone, or testosterone. The pure estrogen receptor (ER) antagonist, ICI 164,384, reversed the growth-inhibitory effect of 17beta-E. 17Beta-estradiol failed directly to reduce in vitro superoxide anion production or to modify xanthine oxidase activity. Therefore, these data indicate that 17beta-E, through an ER-dependent mechanism, specifically and significantly inhibited superoxide anion-mediated SMC proliferation in denuded rat aortic explants.
Cathapermal
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S
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA.
Lavigne
M C
MC
Leong-Son
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M
Alibadi
T
T
Ramwell
P W
PW
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D053284:Polyunsaturated Alkamides; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013481:Superoxides / Q000037:antagonists & inhibitors*; D013739:Testosterone / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D013481:Superoxides; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C051781:ICI 164384; D014969:Xanthine Oxidase; D013936:Thymidine