Comparative properties of the catechol estrogens, I: methylation by catechol-O-methyltransferase and binding to cytosol estrogen receptors.
Five catechol estrogens and two 2-methoxyestrogens were compared for their relative affinity of binding to hypothalamic, pituitary, and uterine cytosol estrogen receptors; and for the kinetics of the catechols' methylation by hepatic catechol-0-methyltransferase. All of the catechol estrogens tested have similar Km's for 0-methylation (9-14 muM). Estrogen receptor affinities, however, differ widely. In hypothalamus, for example, where estradiol-17 beta has a Kd of 0.039 +/- 0.008 nanomolar, 4-hydroxyestradiol also binds tightly (0.12 +/- 0.02 nM), 2-hydroxyestradiol and 4-hydroxyestrone with intermediate affinity (0.26 +/- 0.06 and 0.28 +/- 0.07 nM, respectively), and 2-hydroxyestrone and 2-hydroxyestriol much less well (1.68 +/- 0.79 and 1.27 +/- 0.26 nM, respectively). The binding of the 2-methoxyestrogens is extremely weak. These receptor affinities roughly parallel the potencies of these compounds in altering gonadotropin secretion.
D000077584:2-Methoxyestradiol; D000818:Animals; D001665:Binding Sites; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D004964:Estriol / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006894:Hydroxyestrones / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008745:Methylation; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D013379:Substrate Specificity; D014599:Uterus / Q000378:metabolism
D006894:Hydroxyestrones; D011960:Receptors, Estrogen; C008012:2-hydroxyestriol; D004958:Estradiol; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol; D002394:Catechol O-Methyltransferase; D004964:Estriol; C003655:2-methoxyestrone