2-methoxyestrone and 2-hydroxyestriol

Topics: Animals; Catechols; Enzyme Induction; Estradiol; Estriol; Estrogens; Estrogens, Catechol; Female; Hydroxyestrones; Peroxidases; Rats; Structure-Activity Relationship; Uterus

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.

Topics: 2-Methoxyestradiol; Animals; Binding Sites; Catechol O-Methyltransferase; Cytosol; Estradiol; Estriol; Female; Hydroxyestrones; Hypothalamus; Liver; Methylation; Pituitary Gland; Rats; Receptors, Estrogen; Substrate Specificity; Uterus