Regulation of UDP glucuronosyltransferase genes.

The UDP glucuronosyltransferase (UGT) content of cells and tissues is a major determinant of our response to those chemicals that are primarily eliminated by conjugation with glucuronic acid. There are marked interindividual differences in the content of UGTs in the liver and other organs. The mechanisms that lead to these differences are unknown but are most likely the result of differential UGT gene expression. Several transcription factors involved in the regulation of UGT genes have been identified. These include factors such as Hepatocyte Nuclear Factor 1, CAAT-Enhancer Binding Protein, Octamer transcription Factor 1 and Pbx2, which appear to control the constitutive levels of UGTs in tissues and organs. In addition, UGT gene expression is also modulated by hormones, drugs and other foreign chemicals through the action of proteins that bind and/or sense the presence of these chemicals. These proteins include the Ah receptor, members of the nuclear receptor superfamily, such as CAR and PXR and transcription factors that respond to stress.