CCAAT/enhancer-binding protein P is required for activation of genes for ornithine cycle enzymes by glucocorticoids and glucagon in primary-cultured hepatocytes

Transcription of genes for enzymes of the ornithine cycle is activated by h ormones such as glucocorticoids and glucagon, Promoters and enhancers of se veral genes for the enzymes interact with the CCAAT/enhancer-binding protei n (C/EBP) family of transcription factors, and C/EBP beta has been suggeste d to mediate glucocorticoid response of the gene for arginase, the last enz yme of the cycle. To determine the contribution of C/EBP beta to hormonal r egulation of genes for ornithine cycle enzymes, we examined mice with targe ted disruption of the C/EBP beta gene. Induction of genes for the enzymes b y intraperitoneal injection of dexamethasone and glucagon was almost intact in the liver of C/EBP beta -deficient mice. On the other hand, in primary- cultured hepatocytes derived from C/EBP beta -deficient mice, induction of genes for the first enzyme carbamylphosphate synthetase, as well as for arg inase, in response to dexamethasone and/or glucagon was severely impaired. Therefore, C/EBP beta is required for hormonal induction of the genes for o rnithine cycle enzymes in primary-cultured hepatocytes, while the deficienc y of C/EBP beta is compensated for in vivo. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reser ved.