Effect of estradiol metabolites on prostacyclin synthesis in human endothelial cell cultures

Estradiol can stimulate prostacyclin production in the vessel wall, thereby eliciting vasodilatation. In the present work the effect of the estradiol metabolites estrone, 2-methoxyestrone, 2-methoxyestradiol, and 16 alpha-hyd roxyestrone were investigated to find out if they are also able to stimulat e prostacyclin synthesis. All metabolites triggered an increase of prostacy clin synthesis in human endothelial cells starting at a concentration of 10 (-9) M. The parent substance, 17 beta-estradiol, accomplished this effect o nly starting at a concentration of 10(-8) M. These results indicate that es tradiol metabolites may take part in the estradiol-induced vasodilatation i n vivo. (C) 1999 Elsevier Science Inc.