Xenobiotic-metabolizing cytochromes P450 in ontogeny: evolving perspective

While much is known about inducibility of the xenobiotic-metabolizing forms of cytochrome P450, the Family 1-3 enzymes, less well understood is the purpose for the presence of some of these forms in the developing conceptus. Many cytochrome P450 forms are present in the embryo and fetus, like the anabolic forms in Families 5 and higher, and are known to produce molecules with specific functions, e.g., cholesterol, steroids, and their metabolites necessary for normal physiological functions. As we gain greater understanding of the cell cycle and its regulation, and the roles of nuclear receptors in modulating transcriptional activities, a picture begins to emerge in which cytochrome P450 forms appear as molecule-altering enzymes producing and eliminating ligands associated with nuclear receptor activities. For these CYP enzymes to exert a developmental action, a controlled spatial and temporal expression pattern would be essential. Studies now indicate the existence of such temporal control on the appearance of a number of these enzymes and the necessary coenzyme, NADPH-cytochrome P450 reductase.