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 o f liver-specific transcription factors, one of which is HNF-6. The liver-sp ecific factors HNF-4 and C/EBP alpha respectively stimulate and inhibit tra nscription of the hnf 6 gene. Upon GH stimulation, the affinity of HNF-4 fo r the hnf 6 promoter is increased and the binding of C/EBP alpha is decreas ed. GH therefore controls hnf 6 by a combination of stimulatory and derepre ssive 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 li ver 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, whi ch regulate each other by feed-back and autoregulatory loops. (C) 2000 Else vier Science Ireland Ltd. All rights reserved.