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 (UGT1*1 and UGT1*0) in rats, by reverse transcription and quantitative polymerase chain reaction (RT-PCR). The administration of L-T3 decreased the UGT1*O mRNA by 2.2-fold and that of UGT1*1 by only 1.4-fold. In contrast, thyroidectomy increased the UGT1*O 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 encoding for the UGT1*0 isoform by 3.5-fold and for the UGT1*1 isoform by only twofold. The results indicate for the first time that, although UGT1*1 mRNA is indeed a major transcript, its level is weakly affected by these compounds. In contrast, the minor UGT1*0 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.
Masmoudi
T
T
Formation de Biochimie Pharmacologique, UFR de Pharmacie, Dijon, France.
Mounié
J
J
Artur
Y
Y
Magdalou
J
J
Goudonnet
H
H
D000818:Animals; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D058607:Fibric Acids; D005786:Gene Expression Regulation; D014453:Glucuronosyltransferase / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology*
D058607:Fibric Acids; D007527:Isoenzymes; D012333:RNA, Messenger; C019787:bilirubin glucuronoside glucuronosyltransferase; D014284:Triiodothyronine; D002995:Clofibric Acid; D014453:Glucuronosyltransferase; C019304:ciprofibrate