title: Estrogen inhibits endothelin-1 production and c-fos gene expression in rat aorta.
abstract: In order to clarify the mechanism underlying the preventive effect of estrogen on atherogenesis, we investigated the role of estrogen in the regulation of endothelin-1 (ET-1) production and c-fos mRNA expression, which may contribute to atherogenesis. Plasma ET-1 concentration in ovariectomized rats (OVX) was twice as high as that in sham-operated female rats (Sham). Estradiol replacement in OVX rats (OVX + E) decreased plasma ET-1 to the level in Sham (Sham, 0.68 +/- 0.14; OVX, 1.32 +/- 0.14; OVX + E, 0.85 +/- 0.12 pg/ml). Metabolic clearance rate of ET-1 was similar in these three groups of rats, suggesting that the difference in plasma ET-1 was due to production rather than degradation. Measurement of immunoreactive ET-1 in tissue extract and immunohistochemical examination showed that expression of ET-1 in the aortic smooth muscle cells of OVX was increased. The expression of c-fos mRNA in the aorta was also increased in OVX compared with Sham and OVX + E. Intravenous infusion of ET-1 to Sham induced c-fos expression in the aorta, suggesting the contribution of ET-1 to c-fos expression. Tissue culture study revealed that DNA synthesis was increased in the aorta and femoral artery of OVX. These results suggest that inhibition of ET-1 and c-fos expression is involved in the anti-atherogenic action of estrogen.
authors.affiliation: Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Akishita
authors.forename: Y
authors.initials: Y
authors.lastname: Ouchi
authors.forename: H
authors.initials: H
authors.lastname: Miyoshi
authors.forename: A
authors.initials: A
authors.lastname: Orimo
authors.forename: K
authors.initials: K
authors.lastname: Kozaki
authors.forename: M
authors.initials: M
authors.lastname: Eto
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Toba
authors.forename: H
authors.initials: H
authors.lastname: Orimo
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D019332:Endothelin-1 / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D010052:Ovariectomy; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019332:Endothelin-1; D004967:Estrogens; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D004958:Estradiol; D004247:DNA; C023482:estradiol dipropionate