Multiple UDP-glucuronyltransferases for the glucuronidation of thyroid hormone with preference for 3,3',5'-triiodothyronine (reverse T3).

We have studied the glucuronidation of the thyroid hormones T4, T3 and rT3 by liver microsomes of Wistar, Gunn and WAG rats. Gunn rats have a defect in the gene coding for bilirubin and phenol UDP-glucuronyltransferase (UGT) isoenzymes; WAG rats have a genetic defect in androsterone UGT. In normal Wistar rats UGT activity was approximately 5-fold higher for rT3 than for T4 or T3. UGT activities for T4 and rT3, but not for T3, were impaired in Gunn rats. Conversely, UGT activity for T3, but not for T4 or rT3, was impaired in WAG rats. Thus, in rat liver rT3 is glucuronidated much more rapidly than T4 and T3. Our results support the view that T4 and rT3 are glucuronidated by bilirubin and phenol UGTs and T3 by androsterone UGT.