Minireview: Mechanisms of Growth Hormone-Mediated Gene Regulation

Abstract

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.

Growth hormone is permissive for neoplastic colon growth

“…growth hormone | acromegaly | colon | growth hormone deficiency T he pituitary gland secretes growth hormone (GH), which acts as an endocrine regulator by signaling through membrane-associated GH receptors (GHR) to elicit direct peripheral actions as well as to induce insulin growth factor (IGF1) production (1)(2)(3)(4). Most growth-promoting endocrine actions of GH are mediated by IGF1; however, GH also acts independently of IGF1 to regulate muscle, bone, and adipose tissue functions (5)(6)(7).…”

The fat cell epigenetic signature in post-obese women is characterized by global hypomethylation and differential DNA methylation of adipogenesis genes

“…Some adipogenesis genes with DMS in post-obese women have been reported to be epigenetically regulated e.g. IGF1 [40], SREBF1 [41], KLF5 [42], AHR [43], GDF10 [44], TGFB1 [45], EPAS1 [46] and DLK1 [47]. Differential methylation of adipogenesis genes was accompanied by altered expression in the obese, but not post-obese women.…”

Regulation of lipid metabolism and peroxisome proliferator-activated receptors in rainbow trout adipose tissue by lipolytic and antilipolytic endocrine factors

“…Insulin-like growth factor (IGF)-I is structurally and functionally similar to insulin but is more potent as a growth factor and a metabolic controller in rainbow trout and gilthead sea bream myocytes and adipocytes [10,14,15,18]. In vertebrates, many of the growth-promoting actions of GH are known to be mediated indirectly through the stimulation of IGF transcription, mainly by the liver, or locally by extra hepatic tissues [19], but the mechanisms of action involved in GH proliferative and metabolic effects in fish are not well known [20].…”