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Updated: Jul 11, 2026

Colorimetric Assessment of Deiodinase 1 Activity in Human Liver Microsomes Using the Sandell-Kolthoff Reaction
Published on: April 10, 2026
Hepatic UDP-glucuronosyltransferases responsible for glucuronidation of thyroxine in humans
Yoshihisa Kato1, Shin-ichi Ikushiro, Yoshikazu Emi
1Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan. kato@kph.bunri-u.ac.jp
Abstract:
To clarify the UDP-glucuronosyltransferase (UGT) isoform(s) responsible for the glucuronidation of the thyroid hormone thyroxine (T(4)) in the human liver, the T(4) glucuronidation activities of recombinant human UGT isoforms and microsomes from seven individual human livers were comparatively examined. Among the 12 recombinant human UGT1A and UGT2B subfamily enzymes examined, UGT1A1, UGT1A3, UGT1A9, and UGT1A10 showed definite activities for T(4) glucuronidation. These UGT1A enzymes, with the exception of UGT1A10, were detected in all of the human liver microsomes examined. Interindividual differences in T(4) glucuronidation activity were observed among the microsomes from the seven individual human livers, and the T(4) glucuronidation activity was closely correlated with beta-estradiol 3-glucuronidation activity. Furthermore, Spearman correlation analysis for a relationship between the T(4) glucuronidation activity and the level of UGT1A1, UGT1A3, and UGT1A9 in the microsomes revealed that levels of UGT1A1 and UGT1A3, but not that of UGT1A9, were closely correlated with T(4) glucuronidation activity. T(4) glucuronidation activity in human liver microsomes was strongly inhibited by 26,26,26,27,27,27-hexafluoro-1alpha,23(S),25-trihydroxyvitamin D(3) (an inhibitor of UGT1A3), moderately inhibited by either bilirubin (an inhibitor of UGT1A1) or beta-estradiol (an inhibitor of UGT1A1 and UGT1A9), but not inhibited by propofol (an inhibitor of UGT1A9). These findings indicated strongly that glucuronidation of T(4) in the human liver was mediated by UGT1A subfamily enzymes, especially UGT1Al and UGT1A3, and further suggested that the interindividual differences would come from differences in the expression levels of UGT1A1 and UGT1A3 in individual human livers.
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