Catechol estrogens and thrombosis: differential effect of 2-hydroxyestradiol and estradiol on prostacyclin release.
High estrogen burden states, such as that seen in women who ingest oral contraceptive preparations, are associated with increased thrombosis. In other instances, however, estrogens decrease thrombogenicity. Variations in conversion to active metabolites could explain this paradox. Thus, we examined the influence of estradiol and a major metabolite, 2-hydroxyestradiol (catechol estrogen), on prostacyclin release from cultured human umbilical venous endothelium. In micromolar concentrations, both compounds inhibited prostacyclin (PGI2) release from bradykinin-, arachidonic acid-, and ionophore-stimulated, as well as unstimulated monolayers. However, when thrombin was used to stimulate release, estradiol enhanced, while 2-hydroxyestradiol inhibited, PGI2 formation. These sex steroids probably exert their influence at micromolar concentrations through a non-specific interaction with the cell membrane, and may be of importance in the predisposition to thrombosis suffered by those who use oral contraceptives.
D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002393:Estrogens, Catechol / Q000009:adverse effects; D005260:Female; D006801:Humans; D011453:Prostaglandins / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
D002393:Estrogens, Catechol; D011453:Prostaglandins; D004958:Estradiol; C001390:2-hydroxyestradiol; D011464:Epoprostenol; D013917:Thrombin