We examined the effect of
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) on two
transcription factors,
CAAT/enhancer binding protein-alpha (
C/EBPalpha) and beta (
C/EBPbeta), involved in the coordination of gene expression in adipose and liver. A single dose of
TCDD (100 microg/kg) to male C57BL mice resulted in a time- and dose-dependent decrease in the level of
C/EBPalpha mRNA in adipose tissue and liver, and a reciprocal increase in
C/EBPbeta mRNA. Gel shift analysis using hepatic nuclear extracts from control and
TCDD-treated mice and an
oligonucleotide containing a C/EBP recognition
element revealed a time-dependent change in
DNA-
protein complexes formed. Bands corresponding to
C/EBPalpha, as determined by supershift analysis, diminished in
TCDD-treated animals over a 7-day time period, whereas two new bands corresponding to
C/EBPbeta, not present in control extracts, were increased significantly in treated samples.
TCDD induced
C/EBPbeta mRNA in wild-type mouse
hepatoma cells, but not in
aryl hydrocarbon receptor (
AhR) nuclear translocator-deficient
hepatoma cells. Induction in wild-type
hepatoma cells was antagonized effectively by a molar excess of
alpha-naphthoflavone. These results showed that
TCDD caused rapid, reciprocal changes in
C/EBPalpha and
C/EBPbeta mRNAs and
DNA binding in the adipose and liver of male C57BL mice and induced
C/EBPbeta in
hepatoma cells in an AhR-dependent manner. C/EBPs play vital roles in the coordination of energy homeostasis, and their alteration by
TCDD may provide insight into the mechanism by which
TCDD perturbs energy storage and utilization in vivo.