Disruption of thyroid hormone homeostasis in Ugt1a-deficient Gunn rats by microsomal enzyme inducers is not due to enhanced thyroxine glucuronidation.

Toxicology and Applied Pharmacology
Terrilyn A Richardson, Curtis D Klaassen

Abstract

Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) are thought to increase glucuronidation of thyroxine (T(4)), thus reducing serum T(4), and subsequently increasing thyroid stimulating hormone (TSH). Ugt1a1 and Ugt1a6 mediate T(4) glucuronidation. Therefore, this experiment determined the involvement of Ugt1a enzymes in increased T(4) glucuronidation, decreased serum T(4), and increased TSH after MEI treatment. Male Wistar and Ugt1a-deficient Wistar (Gunn) rats were fed a control diet or diet containing pregnenolone-16α-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum T(4), triiodothyronine (T(3)), and TSH concentrations, hepatic T(4)/T(3) glucuronidation, and thyroid histology and follicular cell proliferation were investigated. PCN, 3-MC, and PCB treatments decreased serum T(4), whereas serum T(3) was maintained in both Gunn and Wistar rats (except for PCB treatment). TSH was increased in Wistar and Gunn rats after PCN (130 and 277%) or PCB treatment (72 and 60%). T(4) glucuronidation in Wistar rats was increased after PCN (298%), 3-MC (85%), and PCB (450%), but was extremely low in Gunn rats, and unchanged after MEI. T(3) gluc...Continue Reading

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Citations

Mar 17, 2020·Toxicology and Applied Pharmacology·Fan YaoLiqiao Zhong

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