title: Binding of 2-hydroxyestradiol and 4-hydroxyestradiol to estrogen receptors from human breast cancers.
abstract: The binding of catechol estrogens, epoxyenones and methoxyestrogens was evaluated using estrogen receptors in cytosol prepared from human breast cancers. The relative affinity of 2-hydroxyestradiol, a metabolite formed in vitro from estradiol-17 beta by breast cancer cells, was indistinguishable from that of estradiol-17 beta. 4-Hydroxyestradiol, which is also a metabolite of estradiol-17 beta, associated with the estrogen receptor with a relative affinity approximately 1.5-fold greater than that of estradiol-17 beta. Epoxyenones and methoxyestrogens were weak competitors compared to the binding of estradiol-17 beta, exhibiting relative affinities 3% or less than the affinity of estradiol-17 beta. Sucrose density gradient centrifugation revealed that both 2- and 4-hydroxyestradiol inhibited the binding of estradiol-17 beta to both the 4S and 8S isoforms of the estrogen receptor in a competitive manner, with a Ki = 0.94 nM for 2-hydroxyestradiol and a Ki = 0.48 nM for 4-hydroxyestradiol. It can be concluded that these data demonstrate a specific receptor-mediated estrogenic action for both of these catechol estrogens.
authors.affiliation: Department of Biochemistry, University of Louisville, KY 40292.
authors.forename: C H
authors.initials: CH
authors.lastname: Van Aswegen
authors.forename: R H
authors.initials: RH
authors.lastname: Purdy
authors.forename: J L
authors.initials: JL
authors.lastname: Wittliff
mesh_terms: D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D002393:Estrogens, Catechol; D011960:Receptors, Estrogen; D004958:Estradiol; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol