From growth hormone-releasing peptides to ghrelin: discovery of new modulators of GH secretion

Lengyel, A. M. J.

doi:10.1590/s0004-27302006000100004

Cited by 14 publications

(8 citation statements)

References 59 publications

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“…In hyperthyroidism we have observed a decrease in GH responsiveness to GHRH while GHRP-6-induced GH release was maintained, which could suggest that thyroid hormones interfere with GHRH-releasing mechanisms, with preservation of GHRP-6-activated pathways (57). Interestingly, we have recently shown that there is a decrease in the GH response to ghrelin in these patients, suggesting that thyroid hormones interfere with additional pathways of GH release activated by ghrelin (58). In type 1 diabetes mellitus the GH response to GHRP-6 and hexarelin is either normal or enhanced, demonstrating that hyperglycemia is unable to decrease the GH release induced by these peptides, differently than in normal subjects (59).…”

Section: Regulation Of Gh Secretion By Ghrp-6 and Ghrelin In Manmentioning

confidence: 77%

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

Lengyel

2006

Braz J Med Biol Res

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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

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Section: Regulation Of Gh Secretion By Ghrp-6 and Ghrelin In Manmentioning

confidence: 77%

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

Lengyel

2006

Braz J Med Biol Res

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“…Ghrelin is the most potent endogenous stimulus of the growth hormone ⁄ insulin-like growth factor I (IGF-I) axis known to date (Kojima et al, 1999;Lengyel, 2006). Furthermore, GHRP-6 can also stimulate IGF-I production in the central nervous system (Frago et al, 2002) and in a neuronal neuropeptide Y (NPY)-producing cell line (Frago et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Growth hormone‐releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin‐like growth factor I

Célix

Chowen

Argente

et al. 2009

Eur J of Neuroscience

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Treatment of the fetal hypothalamic neuronal cell line RCA-6 with growth hormone-releasing peptide 6, an agonist of the ghrelin receptor, or insulin-like growth factor I activates intracellular signalling cascades associated with anti-apoptotic actions. Abnormally high concentrations of glutamate provoke over-excitation of neurons leading to cell damage and apoptosis. Thus, the aim of this study was to investigate whether the administration of growth hormone-releasing peptide 6 and insulin-like growth factor I attenuates monosodium glutamate-induced apoptosis in RCA-6 neurons and the mechanisms involved. Two different mechanisms are involved in glutamate-induced cell death, one by means of caspase activation and the second through activation of a caspase-independent pathway of apoptosis mediated by the translocation of apoptosis-inducing factor. Growth hormone-releasing peptide 6 partially reversed glutamate-induced cell death but not the activation of caspases, suggesting blockage of the caspase-independent cell death pathway, which included interference with the translocation of apoptosis-inducing factor to the nucleus associated with the induction of Bcl-2. In contrast, the addition of insulin-like growth factor I to RCA-6 neurons abolished glutamate-induced caspase activation and cell death. These data demonstrate for the first time a neuroprotective role for growth hormone secretagogues in the caspase-independent cell death pathway and indicate that these peptides have neuroprotective effects independent of its induction of insulin-like growth factor I.

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“…The stimulatory role of ghrelin has also been reported in chicken by acting directly in somatotropes 109,173 . Finally, in mammals, ghrelin has a stimulatory role in GH secretion, as reported, for example, in rats, 174 pigs, 175 primates 176 or humans, 23,177 and other species 178 . Consequently, ghrelin stimulates somatotrope activity in all species studied to date and could, thus, play a relevant role in the modulation of GH release, an effect that would have been conserved during vertebrate evolution.…”

Section: Regulation Of Gh Secretionmentioning

confidence: 75%

Understanding the Multifactorial Control of Growth Hormone Release by Somatotropes

Gahete

Durán-Prado

Luque

et al. 2009

Annals of the New York Academy of Sciences

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Control of postnatal growth is the main, but not the only, role for growth hormone (GH) as this hormone also contributes to regulating metabolism, reproduction, immunity, development, and osmoregulation in different species. Likely owing to this variety of group-specific functions, GH production is differentially regulated across vertebrates, with an apparent evolutionary trend to simplification, especially in the number of stimulatory factors governing substantially GH release. Thus, teleosts exhibit a multifactorial regulation of GH secretion, with a number of factors, from the newly discovered fish GH-releasing hormone (GHRH) to pituitary adenylate cyclase-activating peptide (PACAP) but also gonadotropin-releasing hormone, dopamine, corticotropin-releasing hormone, and somatostatin(s) directly controlling somatotropes. In amphibians and reptiles, GH secretion is primarily stimulated by the major hypothalamic peptides GHRH and PACAP and inhibited by somatostatin(s), while other factors (ghrelin, thyrotropin-releasing hormone) also influence GH release. Finally, in birds and mammals, primary control of GH secretion is exerted by a dual interplay between GHRH and somatostatin. In addition, somatotrope function is modulated by additional hypothalamic and peripheral factors (e.g., ghrelin, leptin, insulin-like growth factor-I), which together enable a balanced integration of feedback signals related to processes in which GH plays a relevant regulatory role, such as metabolic and energy status, reproductive, and immune function. Interestingly, in contrast to the high number of stimulatory factors impinging upon somatotropes, somatostatin(s) stand(s) as the main primary inhibitory regulator(s) for this cell type.

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From growth hormone-releasing peptides to ghrelin: discovery of new modulators of GH secretion

Cited by 14 publications

References 59 publications

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

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

Growth hormone‐releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin‐like growth factor I

Understanding the Multifactorial Control of Growth Hormone Release by Somatotropes

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