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-O-methyltransferase. All of the catechol estrogens tested have similar K_m 's for O-methylation (9–14 μM). Estrogen receptor affinities, however, differ widely. In hypothalamus, for example, where estradiol-17β has a K_d 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.