RT Journal Article SR Electronic T1 Thyroid Hormone Is Necessary for Expression of Constitutive Androstane Receptor in Rat Hepatocytes JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1963 OP 1969 DO 10.1124/dmd.108.022905 VO 37 IS 9 A1 Hidekazu Ooe A1 Junko Kon A1 Hideki Oshima A1 Toshihiro Mitaka YR 2009 UL http://dmd.aspetjournals.org/content/37/9/1963.abstract AB Small hepatocytes are hepatocyte progenitor cells that possess the capability of maturation and cryopreservation. When cryopreserved rat small hepatocytes were cultured in serum-free medium, the protein expression and the inducibility of CYP1A1/2, CYP2E1, and CYP3A were maintained, but those of CYP2B1 were lost. In this study we investigated the cause of the loss of CYP2B1 expression in cryopreserved small hepatocytes by reverse transcription-polymerase chain reaction, immunoblotting, and chromatin immunoprecipitation assay. Expression of mRNA and protein of the nuclear receptor, constitutive androstane receptor (CAR), which regulates the expression of CYP2B1, was inhibited in the serum-free culture of cryopreserved small hepatocytes, whereas they were expressed in that of subcultured small hepatocytes. Serum application dramatically induced CAR expression in the culture of cryopreserved small hepatocytes. The addition of very low concentrations of thyroid hormones (THs; 3,5,3′-triiodothyronine, 5 × 10–12 M; thyroxine, 5 × 10–12-5 × 10–10 M) to the medium also induced the expression of CAR and CYP2B1. Moreover, CYP2B1 expression was induced by administration of phenobarbital. In rats with hypothyroidism induced by thyroidectomy and 6-propyl-2-thiouracil treatment, the expression of CAR and CYP2B1 was strongly repressed. Although THs do not directly regulate the expression of CAR, they may be important for rat hepatocytes to regulate CYP2B1 through CAR expression in the physiological condition.