Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

Abstract

Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides. Correspondence

Role of the GH/IGF-I axis in the growth retardation of weaver mice

“…While GHRH has not been measured in weaver mice, our results do not support the involvement of ghrelin, which stimulates GHRH secretion and amplifies GHRH's effects on the somatotroph [41]. This is deduced from the fact that weaver mice have normal food intake, which is also known to be regulated by ghrelin [41]. On the other hand, somatostatin mRNA levels are 20-87% higher in the weaver mouse hypothalamus as demonstrated by in situ hybridization [42].…”

“…Since homozygous weaver mice are reported to have normal pituitary GH mRNA levels [21], the cause of low GH circulating levels is likely related to the regulation of its release, which is under the control of a complex neuroendocrine network comprising hypothalamic GH releasing hormone, somatostatin, and ghrelin [3]. While GHRH has not been measured in weaver mice, our results do not support the involvement of ghrelin, which stimulates GHRH secretion and amplifies GHRH's effects on the somatotroph [41]. This is deduced from the fact that weaver mice have normal food intake, which is also known to be regulated by ghrelin [41].…”

Growth hormone and growth hormone gene of the American mink (Neovison vison) – the current state of knowledge of one of the key hormones in one of the most intensively economically exploited species

“…The most important synthetic chemical compounds stimulating the GH secretion are apomorphine (APO), propranolol, clonidine and synthetic growth hormone releasing peptide (GHRP), e.g. GHRP-6 and hexarelin (Low, 1991;Scacchi et al, 1999;Lengyel, 2006). The GH level also increases under the influence of glucogenic amino acids (arginine, glycine, glutamine), L-Doop, niacin, opioid peptides, galanin, vitamin A, or glucagon (Morita et al, 1989;Johnson et al, 1993;Zdrojewicz et al, 2000;Gómez et al, 2002;Arwert et al, 2003;Ginalska-Malinowska, Malinowska, 2009;Skottner, 2012;Vught et al, 2012).…”

Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

“…A insulina suprime a secreção do GH e também diminui a expressão do gene, da mesma forma que a somatostatina. Já a ghrelina estimula a secreção do GH por uma via diferente do GHRH (14,16).…”