PT  - JOURNAL ARTICLE
AU  - Yoshinari, Kouichi
AU  - Sueyoshi, Tatsuya
AU  - Moore, Rick
AU  - Negishi, Masahiko
TI  - Nuclear Receptor CAR as a Regulatory Factor for the Sexually Dimorphic Induction of <em>CYP2B1</em> Gene by Phenobarbital in Rat Livers
AID  - 10.1124/mol.59.2.278
DP  - 2001 Feb 01
TA  - Molecular Pharmacology
PG  - 278--284
VI  - 59
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/59/2/278.short
4100  - http://molpharm.aspetjournals.org/content/59/2/278.full
SO  - Mol Pharmacol2001 Feb 01; 59
AB  - The nuclear receptor constitutive active receptor (CAR) translocates into liver nuclei after phenobarbital (PB) treatment, and activates the conserved enhancer called the PB-response element module (PBREM) found in CYP2B genes. We have examined whether CAR regulates the dimorphic induction by PB of the CYP2B1 gene in Wistar Kyoto (WKY) rats. Northern blot analysis showed that PB induced CYP2B1 mRNA in male WKY rats but not female rats. An in situ injected PBREM-luciferase reporter gene was activated by PB only in the male livers. Western blot analysis revealed extremely low levels of CAR in the cytosols of female livers compared with male counterparts. CAR was accumulated in the liver nucleus of male rats in response to PB treatment, whereas the receptor was barely detectable in the liver nuclei of PB-induced females. These sexually dimorphic responses of PBREM and CAR to PB treatment were not observed with Fisher 344 rats, in which CYP2B1 mRNA was induced in both sexes. Thus, these results indicate that CAR is a regulatory factor that leads to the sexual dimorphic induction of CYP2B1 gene in WKY rats.