title: Products of dehydroepiandrosterone metabolism by human mammary tumors and their influence on estradiol receptor binding.
abstract: The high concentrations of dehydroepiandrosterone and its 3beta-sulfate in the blood are potential preocursors for further metabolism by normal and tumorous human mammary tissue. In vitro metabolism of 7n-3H- and 1,2,6,7(n)-3H-dehydroepiandrosterone by fifteen mammary tumors was examined. Some 10--50% of the radioactivity recovered was in the form of 7-oxygenated derivatives: the major metabolite being 7alpha-hydroxydehydroepiandrosterone accompanied by lesser amounts of the 7beta-epimer. 5-Androstene-3beta,17beta-diol was formed in all but one case. Evidence showed that the high yield of 7alpha-hydroxy derivative resulted from direct action of a 7alpha-hydroxylase capable of using both dehydroepiandrosterone and 5-androstene-3beta,17beta-diol as substrates. Although 5-androstene-3beta,17beta-diol competed with estradiol-17beta for the estrogen receptor, this property was considerably reduced as a consequence of the introduction of a 7alpha-hydroxyl or 16alpha-hydroxyl group. Dehydroepiandrosterone, which competed less effectively for the estrogen receptor site, showed almost no affinity for the site upon the introduction of a 7alhpa-hydrocyl group. A regulatory role for the 7alpha-hydroxylase is outlined.
mesh_terms: D000734:Androstenediols / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007526:Isoelectric Point; D011817:Rabbits; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
chemical_list: D000734:Androstenediols; D011960:Receptors, Estrogen; D003687:Dehydroepiandrosterone; D004958:Estradiol