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Endothelial nitric oxide synthase (eNOS) is regulated both by caveolin-1 and 17beta-estradiol (E(2)). Temporal relationships between effects of estrogen on caveolin-1 and nitric oxide (NO) are not known. Therefore, this study was designed to determine whether estrogen regulates caveolin-1 and, if so, whether such regulation corresponds to changes in nitrite/nitrate (NO(x)) production. Bovine aortic endothelial cells (BAECs) were cultured in the absence and presence of 17beta-estradiol or 17alpha-estradiol (10(-8) and 10(-10) M) for 12, 24, and 48 h. eNOS protein expression and NO(x) production increased significantly after 24 h but not after 12-h treatment with 17beta- and not 17alpha-estradiol. Both mRNA and protein for caveolin-1 were increased significantly only after 48-h treatment with E(2), but eNOS protein and NO(x) production were decreased compared with cells treated for 24 h. These increases in caveolin-1 were inhibited by the estrogen receptor antagonist ICI-182,780 (10(-6) M). Results of this study suggest that E(2) stimulates caveolin-1 transcription and translation through estrogen receptor-mediated mechanisms. The results further suggest that estrogen may indirectly regulate NO(x) through caveolin-1 expression, which inhibits eNOS catalytic activity.

Temporal effects of 17β-estradiol on caveolin-1 mRNA and protein in bovine aortic endothelial cells