Catechol estrogens as inhibitors of leukotriene synthesis

Estrogens have a beneficial effect on atherosclerosis and osteoporosis after menopause, but their exact mechanism of action is still unknown. The aim of the present study was to investigate the effects of estradiol and its metabolites catechol estrogens on arachidonic acid metabolism in vitro. Estradiol had no effect on arachidonic acid metabolism up to 33 mu M in A23187-stimulated human whole blood. All catechol estrogens (2-hydroxyestradiol, 2-hydroxyestrone, 4-hydroxyestradiol and 4-hydroxyestrone) had similar kinds of actions on arachidonic acid metabolism, being over ten times more potent inhibitors of leukotriene synthesis (IC50 values 0.044-0.16 mu M) than thromboxane (IC50 values 0.99-2.1 mu M) and prostaglandin E-2 synthesis (IC50 values 0.84-5.5 mu M). It is suggested that some of the protective actions of estrogens-e.g., on atherosclerosis and osteoporosis-may be related to the inhibition of leukotriene synthesis by catechol estrogens. (C) 1998 Elsevier Science Inc.