Control of constitutively-expressed developmentally-activated rat hepatic cytochrome P450 genes.

Abstract

Cytochromes P450 (P450) collectively refer to a superfamily of heme-containing enzymes that use O2 and electrons from NADPH to insert a single atom of oxygen into any one of a large number of substrates. Two general classes of P450s exist; a relatively limited number of P450 forms, expressed in specialized tissues that are associated with pathways of steroidogenesis and a large number of forms responsible for metabolism of foreign compounds. Most of the latter P450s are expressed in liver, the primary site for metabolism of drugs, unusual dietary compounds and environmental pollutants. Numerous forms of P450 are expressed in liver of untreated animals and these are regulated quite differently. Both developmentally-programmed and sex-specific expressions have been observed. In this review, I will summarize recent findings on the mechanisms by which two P450 genes are regulated in livers of developing rats. The CYP2E1 gene is transcriptionally activated within a few hours after birth while the CYP2C6 gene is activated just prior to rats reaching puberty. These genes are under control of two transcription factors, HNF-1 alpha and DBP, respectively, that themselves are developmentally controlled.