Hormonal Regulation of Cytochrome P-450 Gene Expression

This chapter discusses P-450 function and regulation, which should also be of pharmacological relevance—namely, the endocrine regulation of P-450. From a pharmacological perspective, the most significant aspect of the cytochrome P-450 family of proteins is its role in the hepatic metabolism of therapeutic agents. These enzymes have a major influence on the duration of action and on the toxicity of therapeutic agents because they activate, inactivate, and facilitate the excretion of many drugs. Knowledge of the forms of P-450, their substrate specificities, and their regulation is important for the effective therapeutic use of drugs and for understanding and perhaps predicting drug interactions. Sometimes one and the same P-450 gene appears to be multihormonally regulated, indicating the necessity of fine tuning of the specific enzyme activity as a well-balanced response to the current physiological demands of the organism. Such delicate and sophisticated interactive regulatory networks certainly suggest that all P-450 genes express physiologically-essential proteins. This opens up interesting possibilities in the future for development of new therapeutic agents aimed at manipulating tissue levels of those P-450s, which have key roles in various physiological and pathophysiological processes.