EVIDENCE OF THE DIRECTIVE EFFECT OF 17β-CONJUGATE GROUP ON THE ENZYMATIC O-METHYLATION OF CATECHOL ESTROGEN

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Incubations of 2-hydroxyestradiol (I), 2-hydroxyestradiol 17β-sulfate (II), and 2-hydroxyestradiol 17β-glucuronide (III) with purified rat liver catechol O-methyltransferase were carried out at pH 7.2 in the presence of Mg^<2+> and (^3H-Me)-S-adenosyl-L-methionine. The radioactive methylated products, 2-methoxyestradiol (IV) and 2-hydroxyestradiol-3-methyl ether (V), from each substrate were quantificated by reverse isotope dilution method after their complete separation and acetylation. In the experiments of conjugated substrates, II and III, the analyses of the methylated products were done after their hydrolysis of 17β-conjugate groups with acid or β-glucuronidase. The product ratios (2-methoxy/3-methoxy) of substrates I, II, and III, were 1 : 1,4 : 1,and 4.5 : 1,respectively. These results are suggesting that 17β-conjugate groups of 2-hydroxyestradiol has directive effect on enzymatic O-methylation of estrogen catechols. Further, it is estimated that following process may be present in the estradiol metabolism in rat and/or humans : estradiol→estradiol 17β-conjugates→2-hydroxyestradiol 17β-conjugates→2-methoxyestradiol 17β-conjugates.
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