Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats

Visser, Theo J.; Kaptein, Ellen; Harpur, Ernest S.

doi:10.1016/0006-2952(91)90735-n

Cited by 23 publications

(20 citation statements)

References 17 publications

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“…Our results are compatible with the hypothesis that T4 is conjugated by both MC-inducible phenol UGT and fibrate-inducible bilirubin UGT [4,5]. Relative to Tqr however, rT, is by far the preferred substrate for these isoenzymes.…”

Section: Discussionsupporting

confidence: 81%

“…Thus, glucuronidation of T4 in liver is stimulated by treatment of rats with different classes of microsomal enzyme inducers, such as (i) MCtype inducers, including PCBs, dioxin, /3naphtoflavone and hexachlorobenzene [4,6,19-281, (ii) phenobarbital [2429], (iii) the phenoxyisobutyrate derivatives clofibrate, ciprofibrate and nafenopine [5,30,31], (iv) pregnenolone-16a-carbonitrile [25,27,28], and (v) spironolactone [32]. In general, the effects of such treatments on T4 UGT activity are much greater than on T, glucuronidation, while studies of hepatic rT, UGT activity have not been reported .…”

Section: Discussionmentioning

confidence: 99%

“…3-methylcholanthrene (MC)-inducible phenol UGT and clofibrate-inducible bilirubin UGT [4,5]. Glucuronidation of T, shows little response to these treatments.…”

Section: Tissue Preparationsmentioning

confidence: 99%

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

Visser

Kaptein

Raaij³

et al. 1993

FEBS Letters

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We have studied the glucuronidation of the thyroid hormones T4, T, and rT, 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 &fold higher for rT> than for T, or T,. UGT activities for T4 and rT,, but not for T,, were impaired in Gunn rats. Conversely, UGT activity for T,, but not for T, or rT,, was impaired in WAG rats. Thus, in rat liver rT, is glucuronidated much more rapidly than T, and T,. Our results support the view that T, and rT, are glucuronidated by bilirubin and phenol UGTs and T, by androsterone UGT.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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

Visser

Kaptein

Raaij³

et al. 1993

FEBS Letters

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“…Recent studies reported that multiple UGT isoenzymes are involved in this pathway. Thyroxine (T 4 ), the main secretory product of the thyroid gland is glucuronidated by 4-nitrophenol (UGT1A1) and bilirubin UGTs, while T 3 , which is produced by outer ring deiodination of T 4 in peripheral tissues, is glucuronidated by androsterone UGT (14,15). In addition, Visser et al (13) reported that the MC-type inducers also increase T 3 glucuronidation.…”

Section: Discussionmentioning

confidence: 99%

“…However, the molecular basis and the physiological significance of this phenomenon remain to be elucidated. Interestingly, previous studies have implicated the UGT1A1 isoenzyme in the glucuronidation of thyroid hormones (12)(13)(14). Therefore, further investigation of the effect of thyroid hormone on UGT1A1 expression is required to determine the mechanism by which thyroid hormones regulate their own metabolism and stimulate drug glucuronidation and elimination from the liver.…”

Section: Udp-glucuronosyltransferases (Ugts)mentioning

confidence: 99%

Transcriptional Regulation by Triiodothyronine of the UDP-glucuronosyltransferase Family 1 Gene Complex in Rat Liver

Masmoudi

Hihi²,

Vázquez³

et al. 1997

Journal of Biological Chemistry

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This study demonstrates that the expression of the phenol UDP-glucuronosyltransferase 1 gene (UGT1A1) is regulated at the transcriptional level by thyroid hormone in rat liver. Following 3,5,3-triiodo-L-thyronine (T 3 ) stimulation in vivo, there is a gradual increase in the amount of UGT1A1 mRNA with maximum levels reached 24 h after treatment. In comparison, induction with the specific inducer, 3-methylcholanthrene (3-MC), results in maximal levels of UGT1A1 mRNA after 8 h of treatment. In primary hepatocyte cultures, the stimulatory effect of both T 3 and 3-MC is also observed. This induction is suppressed by the RNA synthesis inhibitor actinomycin D, indicating that neither inducer acts at the level of mRNA stabilization. Indeed, nuclear run-on assays show a 3-fold increase in UGT1A1 transcription after T 3 treatment and a 6-fold increase after 3-MC stimulation. This transcriptional induction by T 3 is prevented by cycloheximide in primary hepatocyte cultures, while 3-MC stimulation is only partially affected after prolonged treatment with the protein synthesis inhibitor. Together, these data provide evidence for a transcriptional control of UGT1A1 synthesis and indicate that T 3 and 3-MC use different activation mechanisms. Stimulation of the UGT1A1 gene by T 3 requires de novo protein synthesis, while 3-MC-dependent activation is the result of a direct action of the compound, most likely via the aromatic hydrocarbon receptor complex.

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Xanthohumol, a prenylated chalcone from hops, modulates hepatic expression of genes involved in thyroid hormone distribution and metabolism

Radović

Hussong

Gerhäuser

et al. 2010

Molecular Nutrition Food Res

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In the present study, we analyzed the influence of xanthohumol (XN) on thyroid hormone (TH) distribution and metabolism in rats. A potent and selective competition of XN for thyroxine (T4) binding to transthyretin (IC(50)=1 microM at 1.7 nM [(125)I]T4) was found in human and rat sera in vitro. Female rats treated orally with XN showed increased hepatic expression of T4-binding globulin and decreased transthyretin and albumin. Thyrotropin levels and hepatic type 1 deiodinase activity were moderately increased. Northern blot analysis revealed diminished expression of liver sulfotransferase (Sult1a1) and uridine-diphosphate glucuronosyltransferase (Ugt1a1) after XN treatment. The transcript levels of constitutive androstane receptor (CAR), known to be involved in regulation of enzymes metabolizing hormones, drugs and xenobiotics, was lower in rats treated with >10 mg XN/kg body weight per day. Immunoblot analysis indicates reduced amounts of CAR protein. The phenobarbital-inducible cytochrome P450 mRNA level was decreased in rats treated with >10 mg XN/kg/day, in agreement with reduced CAR protein. Although only moderate changes in TH serum levels were observed, the XN-dependent altered expression of components involved in TH homeostasis might be important not only for hormone metabolism, but also for hepatic phase I and II elimination of drug metabolites and xenobiotics.

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Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats

Cited by 23 publications

References 17 publications

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

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

Transcriptional Regulation by Triiodothyronine of the UDP-glucuronosyltransferase Family 1 Gene Complex in Rat Liver

Xanthohumol, a prenylated chalcone from hops, modulates hepatic expression of genes involved in thyroid hormone distribution and metabolism

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Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats

Cited by 23 publications

References 17 publications

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

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

Transcriptional Regulation by Triiodothyronine of the UDP-glucuronosyltransferase Family 1 Gene Complex in Rat Liver

Xanthohumol, a prenylated chalcone from hops, modulates hepatic expression of genes involved in thyroid hormone distribution and metabolism

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Product

Resources

About

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

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