SUPPRESSION OF C EBP-ALPHA AND INDUCTION OF C/EBP-BETA BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN MOUSE ADIPOSE-TISSUE AND LIVER/

We examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) o n two transcription factors, CAAT/enhancer binding protein-alpha (C/EB P alpha) and beta (C/EBP beta), involved in the coordination of gene e xpression in adipose and liver. A single dose of TCDD (100 mu g/kg) to male C57BL mice resulted in a time- and dose-dependent decrease in th e level of C/EBP alpha mRNA in adipose tissue and liver, and a recipro cal increase in C/EBP beta mRNA. Gel shift analysis using hepatic nucl ear extracts from control and TCDD-treated mice and an oligonucleotide containing a C/EBP recognition element revealed a time-dependent chan ge in DNA-protein complexes formed. Bands corresponding to C/EBP alpha , as determined by supershift analysis, diminished in TCDD-treated ani mals over a 7-day time period, whereas two new bands corresponding to C/EBP beta, not present in control extracts, were increased significan tly in treated samples. TCDD induced C/EBP beta mRNA in wild-type mous e hepatoma cells, but not in aryl hydrocarbon receptor (AhR) nuclear t ranslocator-deficient hepatoma cells. Induction in wild-type hepatoma cells was antagonized effectively by a molar excess of alpha-naphthofl avone. These results showed that TCDD caused rapid, reciprocal changes in C/EBP alpha and C/EBP beta mRNAs and DNA binding in the adipose an d liver of male C57BL mice and induced C/EBP beta 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 insigh t into the mechanism by which TCDD perturbs energy storage and utiliza tion in vivo. (C) 1998 Elsevier Science Inc.