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Thyroxine and 3,3',5-Triiodothyronine Are Glucuronidated in Rat Liver by Different Uridine Diphosphate-Glucuronyltransferases^*

Department of Clinical Chemistry, School of Pharmacy, University of Utrecht (J.B.B., P.K.) Utrecht
Department of Toxicology, Agricultural University of Wageningen (J.G.M.v.E., A.B.) Wageningen
Departments of Internal Medicine HI (H.J.v.d.H., M.d.J., R.D., E.P.K., G.H., T.J.V.) and Nuclear Medicine (M.d.J., E.P.K.), Erasmus University Medical School Rotterdam, The Netherlands

Abstract

Male Wistar rats were treated with 50 mg 3,3',4,4'-tetrachlorobiphenyl (TCB)/kg BW or vehicle. After 4 days, the livers were isolated and perfused for 90 min with 2 nM [¹²⁵I]T₃ or 10 nM [¹²⁵I]T₄ in Krebs-Ringer medium containing 1% albumin. Deiodination and conjugation products and remaining substrates were determined in bile and medium samples by Sephadex LH-20 chromatography and HPLC. TCB treatment did not affect hepatic uptake and metabolism of T₃. However, biliary excretion of T₄ glucuronide was strongly increased by TCB, resulting in an augmented T₄ disappearance from the medium, although initial hepatic uptake of T₄ was not altered. Measurement of the microsomal UDP-glucuronyltransferase (UDPGT) activities confirmed that T₄ UDPGT was induced by TCB, whereas T₃ glucuronidation was unaffected. T₃ UDPGT activity showed a discontinuous variation, which completely matched the genetic heterogeneity in androsterone glucuronidation in Wistar rats. These results indicate that different isozymes catalyze the glucuronidation of T₃ and T₄. (Endocrinology 128: 741–746, 1991)

Footnotes

^* This work was supported in part by the Foundation for Medical lesearch MEDIGON (Grant 900-540-191).

Received June 29, 1990.

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