%0 Journal Article %A Cindy Yanfei Li %A Helen J. Renaud %A Curtis D. Klaassen %A Julia Yue Cui %T Age-specific Regulation of Drug-processing Genes in Mouse Liver by Ligands of Xenobiotic-sensing Transcription Factors %D 2015 %R 10.1124/dmd.115.066639 %J Drug Metabolism and Disposition %P dmd.115.066639 %X The xenobiotic-sensing transcription factors (xeno-sensors) aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) up-regulate the expression of many drug-processing genes (DPGs) in liver. Previous studies have unveiled profound changes in the basal expression of DPGs during development; however, the knowledge of the ontogeny of the inducibility of DPGs in response to pharmacological activation of xeno-sensors is still limited. The goal of this study was to investigate the age-specific regulation of DPGs by prototypical xeno-sensor ligands (TCDD for AhR, TCPOBOP for CAR, and PCN for PXR) during mouse liver development. The basal mRNAs of most DPGs were low during neonatal age, but gradually increased to adult levels, whereas some DPGs (Cyp1a2, Cyp2b10, Cyp3a11, Gstm2, Gstm3, Papss2, and Oatp1a4) exhibited adolescent-predominant expression pattern. The inducibility of DPGs was age-specific: 1) during neonatal age, the highest fold-increase in the mRNA expression was observed for Cyp1a2, Sult5a1 and Ugt1a9 by TCDD; Cyp3a11 and Mrp2 by TCPOBOP; as well as Gstm2 and Gstm3 by PCN; 2) during adolescent age, the highest fold-increase in the mRNA expression was observed for Ugt1a6 and Mrp4 by TCDD; Cyp2b10, Ugt2b34, and Ugt2b35 by TCPOBOP; as well as Gsta1, Gsta4, Sult1e1, Ugt1a1, Mrp3, and Mrp4 by PCN; 3) in adults, the highest fold-increase in the mRNA expression was observed for Aldh1a1, Aldh1a7, and Ugt2b36 by TCPOBOP; as well as Papss2 and Oatp1a4 by PCN. In conclusion, the inducibility of hepatic DPGs following the pharmacological activation of xeno-sensors is age-specific. %U https://dmd.aspetjournals.org/content/dmd/early/2015/11/17/dmd.115.066639.full.pdf