Control of gene expression by growth hormone in liver: key role of a network of transcription factors

Growth hormone (GH) controls gene expression in liver. Recent work suggests that this can result in part from the stimulation by GH of the synthesis of liver-specific transcription factors, one of which is HNF-6. The liver-specific factors HNF-4 and C/EBP alpha respectively stimulate and inhibit transcription of the hnf 6 gene. Upon GH stimulation, the affinity of HNF-4 for the hnf 6 promoter is increased and the binding of C/EBP alpha is decreased. GH therefore controls hnf 6 by a combination of stimulatory and derepressive mechanisms. On the other hand, HNF-6 stimulates transcription of the hnf 3 beta and hnf 4 genes, the stimulation of hnf 4 resulting most likely from the GH-induced increase in HNF-6 concentration. We conclude that in liver GH is likely to control the synthesis of a whole set of proteins whose genes are regulated by a GH-sensitive network of transcription factors, which regulate each other by feed-back and autoregulatory loops. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.