Evidence of the directive effect of 17.BETA.-conjugate group on the enzymatic O-methylation of catechol estrogen.

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Abstract
Incubations of 2-hydroxyestradiol (I), 2-hydroxyestradiol 17.beta.-sulfate (II) and 2-hydroxyestradiol 17.beta.-glucuronide (III) with purified rat liver catechol O-methyltransferase were carried out at pH 7.2 in the presence of Mg2+ and (3H-Me[methyl])-S-adenosyl-L-methionine. The radioactive methylated products, 2-methoxyestradiol and 2-hydroxyestradiol-3-methyl ether, 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 17.beta.-conjugate groups with acid or .beta.-glucuronidase. The product ratios (2-methoxy/3-methoxy) of substrates I, II and III, were 1:1, 4:1 and 45:1, respectively. 17.beta.-Conjugate groups of 2-hydroxyestradiol has directive effect on enzymatic O-methylation of estrogen catechols. The following process may be present in the estradiol metabolism in rat and/or humans: estradiol .fwdarw. estradiol 17.beta.-conjugates .fwdarw. 2-hydroxyestradiol 17.beta.-conjugates .fwdarw. 2-methoxyestradiol 17.beta.-conjugates.