FUNCTIONAL-ROLE OF ESTROGEN METABOLISM IN TARGET-CELLS - REVIEW AND PERSPECTIVES

Cytochrome p450 enzymes that metabolize estrogens are expressed in the mammary gland, uterus, brain and other target tissues for estrogen ac tion, and this results in the formation of hydroxylated estrogens in t hese tissues, Estradiol metabolites formed in target tissues at or nea r estrogen receptors may either be inactive or have important biologic al effects, and changes in the activities of estrogen-metabolizing enz ymes in target tissues may profoundly influence estrogen action, Altho ugh some active estrogen metabolites exert hormonal effects in target tissues by interaction with the classical estrogen receptor, other met abolites appear to elicit unique biological responses that are not ass ociated,vith activation of this receptor, Therefore, some of the many actions of estradiol may not be caused by estradiol per se, but may re sult from the formation of active estrogen metabolite(s) which functio n as local mediators or may activate their own unique receptors or eff ecters, This is an important area in need of more research, The presen t paper represents a review of the literature and perspectives by the authors on the functional role of estrogen metabolism in target tissue s.