Abstract
We investigated by RNase protection the differential expression ofCYP3A4andCYP3A7mRNAs in fetal and adult human livers and in adult hepatocytes in primary culture. Our results show thatCYP3A7is expressed in the liver of 8 of 9 adult Caucasians examined, at an average level of 1.7% of the level found in a fetal liver.CYP3A4mRNA appeared to be expressed in this fetal liver. In adult hepatocytes in primary culture, the constitutive level ofCYP3A4mRNA was low but detectable after 96 hours in untreated cells, butCYP3A7mRNA remained undetectable. However, when the cells were treated for 48 hours with 25μM rifampicin, bothCYP3A4andCYP3A7mRNAs were strongly induced in the 3 and in 2 of 3 cultures examined, respectively. Using an isoelectric focusing immunoblotting the two proteins were resolved. ProteinCYP3A4was detectable in induced cells butCYP3A7was not. These results show for the first time thatCYP3A7andCYP3A4mRNAs, but not the proteins, are co-inducible by rifampicin in adult human hepatocytes in culture.
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