Hepatocyte Nuclear Factor-1α Is a Causal Factor Responsible for Interindividual Differences in the Expression of UDP-Glucuronosyltransferase 2B7 mRNA in Human Livers

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Human dihydrodiol dehydrogenase (DD) catalyses the oxidation of trans-dihydrodiols of polycyclic aromatic hydrocarbons and the reduction of several ketone-containing drugs. About 40-fold interindividual difference in DD activities has been noted. Recently, we found that transcriptional factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha and HNF-4 gamma were essential for the expression of DD4 mRNA, which is a major form of DDs. Thus, to clarify a possible mechanism(s) underlying the interindividual difference in DD activities, we investigated the sequences of genes and the expression levels of mRNA for DD4 and HNFs in human livers. We found no clear relationship between the genotypes of DD4 and HNF genes and the expression levels of DD4 mRNA in the subjects. The expression level of DD4 mRNA significantly correlated with that of HNF-1 alpha, HNF-4 alpha or HNF-4 gamma. These results suggest that the expression level of DD4 mRNA is cooperatively regulated by the amounts of HNF-1 alpha, HNF-4 alpha and HNF-4 gamma.

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Humans Liver Glucuronosyltransferase Isoenzymes Transcription Factors DNA-Binding Proteins Nuclear Proteins Reverse Transcriptase Polymerase Chain Reaction Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha