Minireview: mechanisms of growth hormone-mediated gene regulation.
GH exerts a diverse array of physiological actions that include prominent roles in growth and metabolism, with a major contribution via stimulating IGF-1 synthesis. GH achieves its effects by influencing gene expression profiles, and Igf1 is a key transcriptional target of GH signaling in liver and other tissues. This review examines the mechanisms of GH-mediated gene regulation that begin with signal transduction pathways activated downstream of the GH receptor and continue with chromatin events at target genes and additionally encompasses the topics of negative regulation and cross talk with other cellular inputs. The transcription factor, signal transducer and activator of transcription 5b, is regarded as the major signaling pathway by which GH achieves its physiological effects, including in stimulating Igf1 gene transcription in liver. Recent studies exploring the mechanisms of how activated signal transducer and activator of transcription 5b accomplishes this are highlighted, which begin to characterize epigenetic features at regulatory domains of the Igf1 locus. Further research in this field offers promise to better understand the GH-IGF-1 axis in normal physiology and disease and to identify strategies to manipulate the axis to improve human health.
Department of Pediatrics, Icahn School of Medicine at Mt Sinai, New York, New York 10029.
Dennis J
DJ
Chia
D000818:Animals; D002843:Chromatin / Q000235:genetics; D005786:Gene Expression Regulation; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000254:growth & development; D011986:Receptors, Somatotropin / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I