Hormonal Regulation of Hepatic Drug-Metabolizing Enzyme Activity During Adolescence

Abstract

Activities of drug‐metabolizing enzymes (DMEs) are known to change throughout the course of physical and sexual maturation, with the greatest variability noted during infancy and adolescence. The mechanisms responsible for developmental regulation of DME are currently unknown. However, the hormonal changes associated with puberty/adolescence provide a theoretical framework for understanding the biochemical regulation of DME activity during growth and maturation. Important information regarding potential influences of growth and sex hormones can also be extrapolated from studies that evaluate changes in activities of DMEs occurring as a consequence of physiological, pathological, and/or pharmacological hormonal fluctuations. Collectively, current data support the hypothesis that isoform‐specific alterations in DME activity during adolescence are mediated by sex and/or growth hormones. Characterization of the underlying biochemical alterations responsible for developmental changes in DME activity will require additional studies in which relationships between DMEs and important hormonal axes are evaluated during the course of pubertal development. Clinical Pharmacology & Therapeutics (2008); 84 , 6, 662–673 doi:10.1038/clpt.2008.202