Sexually dimorphic impact of constitutive androstane receptor activation in mouse liver

The constitutive androstane receptor (CAR) is a nuclear receptor able to recognize a large panel of drugs leading to the modulation of the expression of its target genes involved in xenobiotic detoxication and energy metabolism. CAR hepatic activity is thought to be higher in women than in men, but its target genes and metabolic role in female mice have never been thoroughly studied. Here, we investigated the liver gene expression in Car+/+ vs Car-/- male and female C57Bl6/J mice treated with the CAR-specific agonist, 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TPOBOP), or with Corn Oil Car+/+ and Car-/- littermate mice were separated by sex and genotype at 4 weeks and randomly allocated to the different experimental groups: Male Car+/+ Corn Oil (M Car+/+ CO, n=6), Male Car+/+ TCPOBOP (M Car+/+ TCPOBOP, n=6), Male Car-/- Corn Oil (M Car-/- CO, n=6), Male Car-/- TCPOBOP (M Car-/- TCPOBOP, n=6), Female Car+/+ Corn Oil (F Car+/+ CO, n=6), Female Car+/+ TCPOBOP (F Car+/+ TCPOBOP, n=6), Female Car-/- Corn Oil (F Car-/- CO, n=6), Female Car-/- TCPOBOP (F Car-/- TCPOBOP, n=6) (one cage per group). Mice included in TCPOBOP groups received a daily intraperitoneal injection of 1,4-bis[2-(3,5-dichloro pyridyloxy)]Benzene (TCPOBOP, Sigma Aldrich) diluted in corn oil at 3mg/kg for 4 days while CO mice received corn oil only (Sigma Aldrich). At ZT16 (6 hours after the last TCPOBOP injection), mice were anesthetized with Isoflurane and Xylasine (2%, 2mg/kg) and liver samples were collected.