COMPARATIVE QUANTIFICATION OF 2 HEPATIC UDP-GLUCURONOSYLTRANSFERASE BILIRUBIN ISOFORMS MESSENGER-RNA IN VARIOUS THYROID STATES IN RAT

The study was designed to compare the effects of 3,5,3'-triiodo-L-thyr onine (L-T3) on the levels of hepatic mRNAs encoding two UDP-glucurono syltransferase bilirubin isoforms (UGT11 and UGT1*0) in rats, by reve rse transcription and quantitative polymerase chain reaction (RT-PCR). The administration of L-T3 decreased the UGT10 mRNA by 2.2-fold and that of UGT11 by only 1.4-fold. In contrast, thyroidectomy increased the UGT10 mRNA level by twofold but did not change that of the UGT1*1 isoform significantly. Interestingly, treatment with a known inducer of UGT bilirubin, ciprofibrate, induced the hepatic mRNA levels encodi ng for the UGT10 isoform by 3.5-fold and for the UGT1*1 isoform by on ly twofold. The results indicate for the first time that, although UGT 11 mRNA is indeed a major transcript, its level is weakly affected by these compounds. In contrast, the minor UGT10 form is much more sens itive 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. (C) 1991 Else vier Science Inc.