Comparative quantification of two hepatic UDP-glucuronosyltransferase bilirubin isoforms mRNAs in various thyroid states in rat.

The study was designed to compare the effects of 3,5,3' triiodo-L-thyronine (L-T3) on the levels of hepatic mRNAs encoding two UDP-glucuronosyltransferase bilirubin isoforms (UGT11 and UGT10) in rats, by reverse transcription and quantitative polymerase chain reaction (RT-PCR). The administration of L-T3 decreased the UGT1O mRNA by 2.2-fold and that of UGT11 by only 1.4-fold. In contrast, thyroidectomy increased the UGT1O mRNA level by twofold but did not change that of the UGT11 isoform significantly. Interestingly, treatment with a known inducer of UGT bilirubin, ciprofibrate, induced the hepatic mRNA levels encoding for the UGT10 isoform by 3.5-fold and for the UGT11 isoform by only twofold. The results indicate for the first time that, although UGT11 mRNA is indeed a major transcript, its level is weakly affected by these compounds. In contrast, the minor UGT10 form is much more sensitive both to the action of this drug and to changes in thyroid status. The data support the notion that the various members of exon1 of the UGT1 locus have their own individual regulatory region.