Regulation of xenobiotic detoxification by nuclear receptors

Cytochromes P450 (CYP) from families CYPI, CYP2 and CYP3 are involved in xenobiotic detoxication and are regulated by numerous agents including xenobiotics, bile salts and cytokines. Nuclear receptors PXR (Pregnane X Receptor, NR113) and CAR (Constitutive Androstane Receptor, NR1I2) control the expression of distinct but overlapping arrays of genes including the CYP2 and CYP3 families. These receptors are involved in a tangle of regulatory networks including those pathways controlling vitamin D and cholesterol/bile salt homeostasis, are expressed under the control of the glucocorticoid receptor and are inhibited by the short heterodimer partner (SHP). Such functional interferences provide new views for the understanding of xenobiotic adverse effects.