Special report and reviewGhrelin for the gastroenterologist: history and potential
Section snippets
Distribution and localization
In their original experiments, Kojima et al.7 showed that ghrelin was present in large amounts in rat stomach. Taking this together with the fact that ghrelin, when injected intravenously, induces GH release, they proposed that ghrelin was secreted in the stomach and circulated in the bloodstream to act on the pituitary gland. They also showed ghrelin-immunoreactive neurons in the hypothalamic arcuate nucleus and suggested that ghrelin in the arcuate nucleus may either act on the hypothalamus
Ghrelin and growth hormone secretion
Having identified the natural ligand for GHS-R and having shown stimulation of GH secretion by ghrelin in the rat, investigators showed the potency of the peptide on GH release in the same species.24, 25, 26 Human studies have shown a dose-dependent stimulation of GH release with both intravenous infusions and boluses of ghrelin.26, 27, 28 There were no significant adverse effects with doses of up to 500 μg.27 As well as GH release, there were increases in prolactin,27, 28 adrenocorticotropic
Other endocrine activities
As well as the marked increase in GH secretion elicited by ghrelin, there are effects on corticotroph and lactotroph secretion,26, 28, 38, 39 and ghrelin may play a role in glucose homeostasis and insulin secretion.20, 44, 45, 46 Ghrelin administration leads to an increase in prolactin, adrenocorticotropic hormone, cortisol, and aldosterone through mechanisms that are not yet clear.47, 48, 49, 50, 51 It has been suggested that some of the adrenocorticotropic hormone release may depend on a
Effects of ghrelin on feeding and energy homeostasis
During study of synthetic GHSs, it was noted that there was a short-lived increase in appetite after their acute administration,60, 61 and weight gain was noted with chronic systemic administration to immature rodents.3 Several investigators showed that either ICV or intraperitoneal ghrelin stimulated food intake as well as GH secretion in rats25, 26, 62; the orexigenic effect was comparable with that of neuropeptide Y (NPY).63, 64 Later experiments in volunteers by Wren et al.65 showed that
Obesity and eating disorders
Taken cumulatively, these findings suggest that ghrelin is up-regulated under conditions of negative energy balance and down-regulated in the setting of positive energy balance. The fact that ghrelin plasma levels are high in anorexia nervosa and low in obesity has led to speculation regarding a possible role in the pathophysiology of obesity.93 Several studies have established that plasma ghrelin levels are inversely correlated with body mass index (BMI),76, 93, 94, 95, 96 suggesting ghrelin
Cardiovascular and other effects of ghrelin
Previous work with GH and GHS has suggested beneficial hemodynamic effects. GH and insulin-like growth factor-I are essential for both skeletal and myocardial growth106 and may be beneficial in some patients with cardiac failure.107 GHS-R is abundantly expressed in many tissues, including the heart and blood vessels,5, 19, 108 and stimulation of GHS-R prevents cardiac damage after ischemia-reperfusion injury in hypophysectomized rats.109 Hence, it seemed likely that ghrelin would have
Effect of ghrelin on gastric motility and gastric acid secretion
After the initial discovery of ghrelin, Tomasetto et al.8 named the peptide the “motilin-related peptide” because of its structural homology with motilin. The aim of their study was to look for new proteins with expression restricted to the gastric epithelium that may provide insight to the differentiation and function of the gastric unit. They identified a novel mouse cDNA, m46, that encodes a peptide of 117 amino acids whose primary sequence is weakly similar to that of prepromotilin (22%
Conclusions
The discovery of ghrelin as an endogenous ligand for the GHS-R and the subsequent work described previously has widened our understanding of the control of GH secretion and energy homeostasis. Ghrelin increases feeding and weight gain and may have a role to play in the treatment and prevention of obesity; it may also offer a novel therapeutic strategy for the treatment of cancer cachexia. Its role as a prokinetic is not well established in humans, but further research may lead to advances in
References (118)
- et al.
Identification and characterization of a novel gastric peptide hormonethe motilin-related peptide
Gastroenterology
(2000) - et al.
A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control
Regul Pept
(2001) - et al.
Ghrelin-producing cells exist as two types of cells, closed- and opened-type cells, in the rat gastrointestinal tract
Peptides
(2002) - et al.
Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells
J Biol Chem
(2002) - et al.
Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats
Biochem Biophys Res Commun
(2000) - et al.
Chicken ghrelin and growth hormone-releasing peptide-2 inhibit food intake of neonatal chicks
Eur J Pharmacol
(2002) - et al.
Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats
Biochem Biophys Res Commun
(2001) - et al.
Inhibition of pancreatic protein secretion by ghrelin in the rat
J Physiol
(2001) - et al.
Intracerebroventricular growth-hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats
Life Sci
(1995) - et al.
Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release
Eur J Pharmacol
(1998)
Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin
Gastroenterology
Current status of medical and surgical therapy for obesity
Gastroenterology
Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats
Gastroenterology
Ghrelin-leptin tango in body-weight regulation
Gastroenterology
The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats
Gastroenterology
A study on the regulation of growth hormone release from the pituitaries of rats in vitro
Endocrinology
New advances on the regulation of growth hormone (GH) secretion
Int J Neurol
On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone
Endocrinology
Mechanisms of action of a second generation growth hormone-releasing peptide (Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) in rat anterior pituitary cells
Endocrinology
A receptor in pituitary and hypothalamus that functions in growth hormone release
Science
Peptidomimetic regulation of growth hormone secretion
Endocr Rev
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Nature
Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans
Endocrinology
Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery
N Engl J Med
Helicobacter pylori has no effect on plasma ghrelin levels
Eur J Endocrinol
Plasma ghrelin following cure of Helicobacter pylori
Gut
Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans
J Clin Endocrinol Metab
Gender and gonadal influences on ghrelin mRNA levels in rat stomach
Eur J Endocrinol
Ghrelin, a novel placental-derived hormone
Endocrinology
The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans
J Clin Endocrinol Metab
Growth hormone secretagogue binding sites in peripheral human tissues
J Clin Endocrinol Metab
Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion
Diabetes
GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils
J Clin Endocrinol Metab
Novel expression and functional role of ghrelin in rat testis
Endocrinology
Ghrelin induces adiposity in rodents
Nature
The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion
Endocrinology
Ghrelin-induced growth hormone secretion in humans
Eur J Endocrinol
Ghrelin strongly stimulates growth hormone release in humans
J Clin Endocrinol Metab
Rat ghrelin stimulates growth hormone and prolactin release in the tilapia, Oreochromis mossambicus
Zoolog Sci
Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland
Recent Prog Horm Res
Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficient patients with mutated GH-releasing hormone receptor
J Clin Endocrinol Metab
Growth hormone-releasing peptide (GHRP)
Cell Mol Life Sci
Regulational effect of ghrelin on growth hormone secretion from perifused rat anterior pituitary cells
J Neuroendocrinol
Desensitization studies using perifused rat pituitary cells show that growth hormone-releasing hormone and His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 stimulate growth hormone release through distinct receptor sites
J Endocrinol
Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone
J Clin Endocrinol Metab
Growth hormone-releasing peptides
Eur J Endocrinol
Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humanscomparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone
J Clin Endocrinol Metab
A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans
J Clin Endocrinol Metab
Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance
Am J Physiol Endocrinol Metab
A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
Diabetes
Cited by (83)
Ghrelin as an anti-inflammatory and protective agent in ischemia/reperfusion injury
2020, PeptidesCitation Excerpt :Ghrelin has a pleiotropic effect and is a hormone involved in the central control of appetite. Many protective properties of this peptide have been reported in several models with gastric mucosa impairment, including stress and I/R [94–96]. A peripheral and central administration of ghrelin at different times of the I/R period was evaluated and demonstrated its role in the modulation of resistance of the intestinal mucosa to the injury induced by ischemia and subsequent reperfusion.
Toward a Better Drug for Gastroparesis: The Problem With a Moving Target
2016, GastroenterologyBariatric embolization of the gastric arteries for the treatment of obesity
2015, Journal of Vascular and Interventional RadiologyHistopathologic and immunohistochemical sequelae of bariatric embolization in a porcine model
2014, Journal of Vascular and Interventional RadiologyVoluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages
2011, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Initial interest in ghrelin has focused on its appetite-stimulant effects. Further investigation revealed that ghrelin has diverse biologic functions, both in vivo and in vitro, that extend beyond its effects on the central nervous system [10,11]. Recently, new evidence has pointed toward the potential role of ghrelin in influencing the immune system.
Helicobacter pylori Infection: Protective Against Increased Interdialytic Weight Gain in Asymptomatic Hemodialysis Patients?
2011, Journal of Renal NutritionCitation Excerpt :It has been hypothesized that infection with H pylori may impair the synthesis and release of ghrelin. Moreover, it was demonstrated that plasma ghrelin levels were increased after the cure of H pylori, which resulted in increased appetite and weight gain.7,8 In contrast, in another study, no significant difference in plasma ghrelin levels was reported between women of similar age and BMI, who tested either positive or negative for H pylori.24