Temporal effects of 17beta-estradiol on caveolin-1 mRNA and protein in bovine aortic endothelial cells.
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.
Jayachandran
M
M
Department of Geriatrics, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Hayashi
T
T
Sumi
D
D
Iguchi
A
A
Miller
V M
VM
D000818:Animals; D001011:Aorta; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors
D051242:Caveolin 1; D022461:Caveolins; D004965:Estrogen Antagonists; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D000077267:Fulvestrant; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III