Evidence of the directive effect of 17 beta-conjugate group on the enzymatic O-methylation of catechol estrogen.
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)-S-adenosyl-L-methionine. The radioactive methylated products, 2-methoxyestradiol (IV) and 2-hydroxyestradiol-3-methyl ether (V), from each substrate were quantificanted 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. These results are suggesting that 17 beta-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 leads to estradiol 17 beta-conjugates leads to 2-hydroxyestradiol 17 beta-conjugates leads to 2-methoxyestradiol 17 beta-conjugates.
D000818:Animals; D002396:Catechols / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D002393:Estrogens, Catechol; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008745:Methylation; D051381:Rats
D002396:Catechols; D004967:Estrogens; D002393:Estrogens, Catechol; D004958:Estradiol