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Expert opinion on drug metabolism & toxicology

Glucocorticoids and phenobarbital induce murine CYP2B genes by independent mechanisms.


PMID 19732027

Abstract

Genes for CYP of the 2B subfamily (CYP2B genes) have long been known to be inducible in murine liver by phenobarbital and phenobarbital-like inducers. More recently, it has become clear that glucocorticoids can also induce these genes by a mechanism independent of that of phenobarbital-like inducers. To summarize the evidence for the existence of two distinct molecular mechanisms for induction of murine CYP2B genes and to analyze the wider implications of this situation for inducible xenobiotic metabolism. The mechanism of action of phenobarbital-like inducers of murine CYP2B genes is first briefly summarized. The role of glucocorticoids in the induction of various proteins, particularly rat phosphoenolpyruvate carboxykinase, where transcriptional activation is achieved via a glucocorticoid response unit, is also discussed. Finally, recent results are presented on glucocorticoid induction of murine CYP2B genes, including evidence for the presence of a functional glucocorticoid response unit in the rat CYP2B2 gene and for the role of constitutive androstane receptor as an accessory factor in this response. Murine CYP2B genes are seen to respond to two distinct regulatory mechanisms, but much remains to be learned concerning the interactions between these two regulatory loops, as well as the details of glucocorticoid induction.