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Vol. 59, Issue 2, 278-284, February 2001
Pharmacogenetics Section, Laboratory of Reproductive and
Developmental Toxicology, National Institute of Environmental Health
Sciences, National Institutes of Health, Research Triangle Park, North
Carolina
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.
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