Thyroxine and 3,3',5-triiodothyronine are glucuronidated in rat liver by different uridine diphosphate-glucuronyltransferases

Thyroxine and 3,3',5-triiodothyronine are glucuronidated in rat liver by different uridine diphosphate-glucuronyltransferases

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 remaini...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) Vol. 128; no. 2; p. 741
Main Authors: Beetstra, J B, van Engelen, J G, Karels, P, van der Hoek, H J, de Jong, M, Docter, R, Krenning, E P, Hennemann, G, Brouwer, A, Visser, T J
Format: Journal Article
Language:English
Published: United States 01-02-1991
Subjects:
Animals
Glucuronates - metabolism
Glucuronosyltransferase - metabolism
Isoenzymes - metabolism
Liver - metabolism
Male
Polychlorinated Biphenyls - pharmacology
Rats
Rats, Inbred Strains
Thyroxine - blood
Thyroxine - metabolism
Triiodothyronine - blood
Triiodothyronine - metabolism
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Summary: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.
ISSN:0013-7227
DOI:10.1210/endo-128-2-741