To investigate the mechanism underlying the antiatherogenic effect of estrogen, we examined the role of estrogen in the regulation of endothelin-1 (ET-1) production by cultured bovine carotid arterial endothelial cells. Treatment of the cells with 17 beta-estradiol dose dependently inhibited gene expression and peptide secretion of ET-1. This inhibitory effect of 17 beta-estradiol was more marked when ET-1 production was stimulated by transforming growth factor-beta 1. Simultaneous addition of ICI 182,780, a pure estrogen receptor antagonist, completely blocked the effect of 17 beta-estradiol, indicating that 17 beta-estradiol acted via estrogen receptor. These results suggest that reduced ET-1 production by endothelial cells may be involved in the vasoprotective effect of estrogen. (C) 1998 Academic Press.