Regulation of Phase II Biotransformation Enzymes by Steroid Hormones

Phase II biotransformation enzymes conjugate xenobiotics using small, organic donor molecules, such as glutathione, UDP-glucuronic acid, S-adenosyl-L-methionine, acetyl coenzyme A and amino acids (primarily glycine). These reactions generally resulted in detoxification by the loss of pharmacological activity and by quickening the elimination of xenobiotics from the body, however Bioactivation is also known to be occurred. Historically, it was placed more emphasis on research of phase I than of phase II enzymes. Nevertheless, it is well known that conjugation enzymes play an important role in drug and toxicant disposition since they can dramatically alter pharmacokinetics and therefore therapeutic efficacy and toxicity of drugs. In this context surprisingly, the exact regulation mechanism of phase II conjugation enzymes expression is not fully understood. However, available experimental data suggest that several transcriptional factors are involved in this process. In the current review, we characterize and summarize our knowledge about regulation of the most important phase II enzymes, such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), glutathione S-transferases (GSTs), arylamine N-acetyltransferases (NATs), catechol O-methyltransferase (COMT) and thiopurine S-methyltransferase (TPMT) by different steroid hormones.