Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents

CYP3A4 and CYP4A5 share specificity for a wide range of xenobiotics with the CYP3 subfamily collectively involved in the biotransformation of approximately 30% of all drugs. CYP3A4/5 mRNA transcripts have been reported in the skin, yet knowledge of their protein expression and function is lacking. In this study, we observed gene and protein expression of CYP3A4/5 in both human skin and tissue-engineered skin equivalents (TESEs), and enzyme activity was detected using the model substrate benzyl-O-methyl-cyanocoumarin. Mass spectrometric analysis of TESE lysates following testosterone application revealed a time-dependent increase in metabolite production, confirming the functional expression of these enzymes in skin.