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Ghrelin
Kinds of Ghrelin Terms modified by Ghrelin Selected AbstractsGhrelin: a new peptide regulating the neurohormonal system, energy homeostasis and glucose metabolismDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2008Peter Pusztai Abstract Identification of ghrelin started with the discovery of growth hormone secretagogues, continued with the description of ghrelin receptors and ended with the elucidation of the chemical structure of ghrelin. However, several issues concerning the role of ghrelin in physiological and pathophysiological processes are still under investigation. Most of the ghrelin produced in the body is secreted in the stomach, but it is also expressed in the hypothalamus, pituitary, pancreas, intestine, kidney, heart and gonads. Ghrelin stimulates growth hormone secretion via growth hormone secretagogue receptors. Ghrelin secretion in the stomach depends on both acute and chronic changes in nutritional status and energy balance. Current data support the hypothesis that the stomach, in addition to its important role in digestion, not only influences pituitary hormone secretion but, via ghrelin production, it also sends orexigenic (appetite increasing) signals to hypothalamic nuclei involved in the regulation of energy homeostasis. In addition to these main effects, ghrelin influences insulin secretion and glucose metabolism and it may exert potentially important effects on cardiovascular and gastrointestinal functions. Because of its effects on a large number of physiological functions, ghrelin may be involved in the pathomechanism of several human disorders, including disturbances of appetite, energy homeostasis and glucose metabolism. Further research might lead to a better understanding of the pathophysiology of ghrelin and might provide more effective therapy for the above disorders. Copyright © 2008 John Wiley & Sons, Ltd. [source] Ghrelin levels are reduced in prepubertal epileptic children under treatment with carbamazepine or valproic acidEPILEPSIA, Issue 2 2010Flavia Prodam Summary A relationship between ghrelin and epilepsy has been already shown in humans, although the results are controversial. Ghrelin levels are reduced in obesity. Epileptic patients progressively develop a therapy-linked weight gain; however, the mechanisms for this have not been fully explained. The aim of our study is to evaluate if ghrelin secretion is modulated by treatment with carbamazepine or valproic acid in young prepubertal epileptic children. Ghrelin levels were reduced in normal-weight young epileptic prepubertal children under treatment with carbamazepine (p < 0.0001) or valproic acid (p < 0.006) compared to healthy age- and weight-matched subjects. Ghrelin was also lower in children under carbamazepine when compared to those under valproic acid (p < 0.01). A derangement in ghrelin secretion in epilepsy during specific pharmacologic therapies and independent of weight gain could be hypothesized. [source] Ghrelin and insulin metabolismEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2003O. Ukkola No abstract is available for this article. [source] PRECLINICAL STUDY: Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbensADDICTION BIOLOGY, Issue 1 2007Elisabet Jerlhag ABSTRACT Ghrelin stimulates appetite, increases food intake and causes adiposity by mechanisms that include direct actions on the brain. Previously, we showed that intracerebroventricular administration of ghrelin has stimulatory and dopamine-enhancing properties. These effects of ghrelin are mediated via central nicotine receptors, suggesting that ghrelin can activate the acetylcholine,dopamine reward link. This reward link consists of cholinergic input from the laterodorsal tegmental area (LDTg) to the mesolimbic dopamine system that originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens. Given that growth hormone secretagogue receptors (GHSR-1A) are expressed in the VTA and LDTg, brain areas involved in reward, the present series of experiments were undertaken to examine the hypothesis that these regions may mediate the stimulatory and dopamine-enhancing effects of ghrelin, by means of locomotor activity and in vivo microdialysis in freely moving mice. We found that local administration of ghrelin into the VTA (1 µg in 1 µl) induced an increase in locomotor activity and in the extracellular concentration of accumbal dopamine. In addition, local administration of ghrelin into the LDTg (1 µg in 1 µl) caused a locomotor stimulation and an increase in the extracellular levels of accumbal dopamine. Taken together, this indicates that ghrelin might, via activation of GHSR-1A in the VTA and LDTg, stimulate the acetylcholine,dopamine reward link, implicating that ghrelin is a part of the neurochemical overlap between the reward systems and those that regulate energy balance. [source] Helicobacter pylori Infection is Associated with Reduced Circulating Ghrelin Levels Independent of Body Mass IndexHELICOBACTER, Issue 5 2005Akiko Shiotani ABSTRACT Background., Ghrelin stimulates growth hormone and has orexigenic and adipogenic effects. Plasma ghrelin levels are reduced in obesity and possibly in Helicobacter pylori infection. Aim., To investigate whether there was a relation between H. pylori infection, body mass index (BMI) and serum ghrelin or leptin levels. Methods., University students undergoing an annual health check-up were invited to participate. H. pylori status was based on the presence of specific IgG H. pylori antibodies in urine. Fasting serum ghrelin, leptin levels, and pepsinogen I and II levels were measured by enzyme immunoassay (EIA). Results., Eight hundred and one students volunteered. There was no significant difference in the height and BMI between those with and without H. pylori infection. The population of ghrelin study consisted of 132 (66 H. pylori -positive and 66 H. pylori -negative) students matched for age, sex, and BMI. The ghrelin level in the H. pylori -positive group was significantly lower (median 55 pmol/l) compared to the H. pylori- negative group (103 pmol/l) (p < .00001). Leptin, triglyceride, total cholesterol, and HDL-cholesterol were not different between the two groups, whereas LDL-cholesterol levels were significantly higher (106 versus 100 mg/dl) (p = .03) in the H. pylori -positive group. Leptin levels correlated with the BMI (r = 0.53) (p < .00001). Among H. pylori -positive subjects, ghrelin correlated only with pepsinogen I levels (r = 0.26, p = .04). Conclusions.,H. pylori infection was associated with a reduction in circulating ghrelin levels independent of sex and BMI. [source] Ghrelin and Bone: Is There an Association in Older Adults?: The Rancho Bernardo Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2006Lauren A Weiss Abstract Laboratory studies suggest that ghrelin is involved in bone metabolism, but studies of ghrelin and bone in humans are limited. We studied sex-specific associations of ghrelin with BMD, NTX, and bone loss. Ghrelin was not associated with BMD or bone loss in either sex. There was a significant inverse association with NTX in men but not in women. Introduction: Ghrelin is a gastric hormone recently shown to be associated with bone metabolism in animal and in vitro studies. Studies in humans are limited. We investigated the association of ghrelin with BMD, the bone resorption marker N-telopeptide (NTX), and bone loss in older men and women. Materials and Methods: Participants were 977 community-dwelling men and non,estrogen-using postmenopausal women, 50,91 years of age. Plasma ghrelin was measured by radioimmunoassay from blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. Axial BMD measurements were repeated an average of 4 years later in 544 participants. Bone turnover was assessed by NTX in urine obtained at the same time as the initial BMD. Multiple regression analyses were used to test sex-specific associations of ghrelin with BMD, NTX, and bone loss in both sexes. Results: No significant ghrelin,BMD or ghrelin,bone loss associations were observed in either sex, after adjusting for age and body mass index (BMI). Ghrelin was inversely associated with NTX in men and positively associated with NTX in women, independent of age. After adjusting for both age and BMI, this association reached statistical significance in men and was weakened in women. Conclusions: Ghrelin may be associated with bone turnover, but there is no evidence for an association with BMD or short-term change in BMD in older adults. [source] Ghrelin Directly Regulates Bone Formation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005Nobuhiro Fukushima Abstract To clarify the role of ghrelin in bone metabolism, we examined the effect of ghrelin in vitro and in vivo. Ghrelin and its receptor, GHS-R1a, were identified in osteoblasts, and ghrelin promoted both proliferation and differentiation. Furthermore, ghrelin increased BMD in rats. Our results show that ghrelin directly affects bone formation. Introduction: Ghrelin is a gut peptide involved in growth hormone (GH) secretion and energy homeostasis. Recently, it has been reported that the adipocyte-derived hormone leptin, which also regulates energy homeostasis and opposes ghrelin's actions in energy homeostasis, plays a significant role in bone metabolism. This evidence implies that ghrelin may modulate bone metabolism; however, it has not been clarified. To study the role of ghrelin in skeletal integrity, we examined its effects on bone metabolism both in vitro and in vivo. Materials and Methods: We measured the expression of ghrelin and growth hormone secretagogue receptor 1a (GHS-R1a) in rat osteoblasts using RT-PCR and immunohistochemistry (IHC). The effect of ghrelin on primary osteoblast-like cell proliferation was examined by recording changes in cell number and the level of DNA synthesis. Osteoblast differentiation markers (Runx2, collagen ,1 type I [COLI], alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR. We also examined calcium accumulation and ALP activity in osteoblast-like cells induced by ghrelin. Finally, to address the in vivo effects of ghrelin on bone metabolism, we examined the BMD of Sprague-Dawley (SD) rats and genetically GH-deficient, spontaneous dwarf rats (SDR). Results: Ghrelin and GHS-R1a were identified in osteoblast-like cells. Ghrelin significantly increased osteoblast-like cell numbers and DNA synthesis in a dose-dependent manner. The proliferative effects of ghrelin were suppressed by [D-Lys3]-GHRP-6, an antagonist of GHS-R1a, in a dose-dependent manner. Furthermore, ghrelin increased the expression of osteoblast differentiation markers, ALP activity, and calcium accumulation in the matrix. Finally, ghrelin definitely increased BMD of both SD rats and SDRs. Conclusions: These observations show that ghrelin directly stimulates bone formation. [source] The Ghrelin/Obestatin Balance in the Physiological and Pathological Control of Growth Hormone Secretion, Body Composition and Food IntakeJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010R. Hassouna Ghrelin and obestatin are two gastrointestinal peptides obtained by post-translational processing of a common precursor, preproghrelin. Ghrelin is an orexigenic and adipogenic peptide and a potent growth hormone secretagogue (GHS) modified by the enzyme ghrelin- O -acyl-transferase to bind and activate its receptor, the GHS-R. The ghrelin/GHS-R pathway is complex and the effects of ghrelin on GH secretion, adiposity and food intake appear to be relayed by distinct mechanisms involving different transduction signals and constitutive activity for the GH-R, different cofactors as modulators of endogenous ghrelin signalling and/or alternative ghrelin receptors. The discovery of obestatin in 2005 brought an additional level of complexity to this fascinating system. Obestatin was initially identified as an anorexigenic peptide and as the cognate ligand for GPR39, but its effect on food intake and its ability to activate GPR39 are still controversial. Although several teams failed to reproduce the anorexigenic actions of obestatin, this peptide has been shown to antagonise GH secretion and food intake induced by ghrelin and could be an interesting pharmacological tool to counteract the actions of ghrelin. Ghrelin and obestatin immunoreactivities are recovered in the blood with an ultradian pulsatility and their concentrations in plasma vary with the nutritional status of the body. It is still a matter of debate whether both hormones are regulated by independent mechanisms and whether obestatin is a physiologically relevant peptide. Nevertheless, a significant number of studies show that the ghrelin/obestatin ratio is modified in anorexia nervosa and obesity. This suggests that the ghrelin/obestatin balance could be essential to adapt the body's response to nutritional challenges. Although measuring ghrelin and obestatin in plasma is challenging because many forms of the peptides circulate, more sensitive and selective assays to detect the different preproghrelin-derived peptides are being developed and may be the key to obtaining a better understanding of their roles in different physiological and pathological conditions. [source] Systemic Administration of Ghrelin Induces Fos and Egr-1 Proteins in the Hypothalamic Arcuate Nucleus of Fasted and Fed RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2000A. K. Hewson Abstract Ghrelin, a recently identified endogenous ligand for the growth hormone secretagogue (GHS) receptor, induces growth hormone (GH) secretion following systemic administration. We sought to determine whether systemic administration of ghrelin activates cells in the hypothalamic arcuate nucleus by examining the distribution of cells expressing Fos and Egr-1 proteins. In normally fed rats, both ghrelin and GHRP-6 (a synthetic GHS) significantly increased the number of cells expressing Fos and Egr-1 in the arcuate nucleus. The effects of ghrelin and GHRP-6 to induce Fos or Egr-1 protein expression was significantly greater in fasted than in fed rats. Thus, we show that (i) ghrelin is a centrally active peptide; (ii) it acts in a similar manner to synthetic GHS; and (iii) its central actions are increased in fasting, presumably reflecting physiological changes that accompany altered food intake and/or nutritional state. [source] Serum ghrelin, leptin and resistin levels in adolescent girls with polycystic ovary syndromeJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2008Aysun Bideci Abstract Aim:, The aim of the present study was to investigate the levels of leptin, resistin and ghrelin in polycystic ovary syndrome (PCOS), and to assess their possible correlations with the hormonal and metabolic features of PCOS. Methods:, Sixteen obese (ObPCOS) and 12 lean (LeanPCOS) subjects with PCOS and 19 obese control subjects were enrolled in the study. Results:, Ghrelin, leptin and resistin concentrations were similar between groups when body mass index (BMI) was used as a covariate (P > 0.05). Mean androgen, SHBG, luteinizing hormone (LH) levels and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio tended to be similar between polycystic ovary syndrome (PCOS) groups. However, when compared with the control group, SHBG was lower and androgen, LH levels and LH/FSH ratio were higher in the PCOS groups. Free testosterone levels significantly correlated with resistin (r = ,0.38), SHBG correlated significantly with body mass index (BMI) (r = ,0.45) and resistin (r = ,0.67), LH/FSH ratio was significantly correlated with ghrelin (r = ,0.52) and estradiol (E2) levels (r = 0.51). Conclusion:, ObPCOS and LeanPCOS groups having higher LH/FSH ratios and lower SHBG levels suggest that there could be factors other than adiposity responsible for the clinical features of PCOS patients. In the light of our results, those factors can be suggested as ghrelin and E2 for the elevated LH/FSH ratio and resistin for the lowered SHBG. [source] Ghrelin Receptor Antagonism Decreases Alcohol Consumption and Activation of Perioculomotor Urocortin-Containing NeuronsALCOHOLISM, Issue 9 2010Simranjit Kaur Background:, The current therapies for alcohol abuse disorders are not effective in all patients, and continued development of pharmacotherapies is needed. One approach that has generated recent interest is the antagonism of ghrelin receptors. Ghrelin is a gut-derived peptide important in energy homeostasis and regulation of hunger. Recent studies have implicated ghrelin in alcoholism, showing altered plasma ghrelin levels in alcoholic patients as well as reduced intakes of alcohol in ghrelin receptor knockout mice and in mice treated with ghrelin receptor antagonists. The aim of this study was to determine the neuroanatomical locus/loci of the effect of ghrelin receptor antagonism on alcohol consumption using the ghrelin receptor antagonist, D-Lys3-GHRP-6. Methods:, In Experiment 1, male C57BL/6J mice were injected with saline 3 hours into the dark cycle and allowed access to 15% (v/v) ethanol or water for 2 hours in a 2-bottle choice experiment. On test day, the mice were injected with either saline or 400 nmol of the ghrelin receptor antagonist, D-Lys3-GHRP-6, and allowed to drink 15% ethanol or water for 4 hours. The preference for alcohol and alcohol intake were determined. In Experiment 2, the same procedure was followed as in Experiment 1 but mice were only allowed access to a single bottle of 20% ethanol (v/v), and alcohol intake was determined. Blood ethanol levels were analyzed, and immunohistochemistry for c-Fos was carried out to investigate changes in neural activity. To further elucidate the mechanism by which D-Lys3-GHRP-6 affects alcohol intake, in Experiment 3, the effect of D-Lys3-GHRP-6 on the neural activation induced by intraperitoneal ethanol was investigated. For the c-Fos studies, brain regions containing ghrelin receptors were analyzed, i.e. the perioculomotor urocortin population of neurons (pIIIu), the ventral tegmental area (VTA), and the arcuate nucleus (Arc). In Experiment 4, to test if blood ethanol concentrations were affected by D-Lys3-GHRP-6, blood samples were taken at 2 time-points after D-Lys3-GHRP-6 pretreatment and systemic ethanol administration. Results:, In Experiment 1, D-Lys3-GHRP-6 reduced preference to alcohol and in a follow-up experiment (Experiment 2) also dramatically reduced alcohol intake when compared to saline-treated mice. The resulting blood ethanol concentrations were lower in mice treated with the ghrelin receptor antagonist. Immunohistochemistry for c-Fos showed fewer immunopositive cells in the pIIIu of the antagonist-treated mice but no difference was seen in the VTA or Arc. In Experiment 3, D-Lys3-GHRP-6 reduced the induction of c-Fos by intraperitoneal ethanol in the pIIIu but had no effect in the VTA. In the Arc, there was a significant increase in the number of c-Fos immunopositive cells after D-Lys3-GHRP-6 administration, but the antagonist had no effect on ethanol-induced expression of c-Fos. D-Lys3-GHRP-6-pretreatment also did not affect the blood ethanol concentrations observed after a systemic injection of ethanol when compared to saline-pretreated mice (Experiment 4). Conclusions:, These findings indicate that the action of ghrelin on the regulation of alcohol consumption may occur via the pIIIu. [source] Orexigenic Peptides and Alcohol Intake: Differential Effects of Orexin, Galanin, and GhrelinALCOHOLISM, Issue 11 2007Eve R. Schneider Background:, The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. Methods:, Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection. Results:, In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake. Conclusions:, In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse. [source] Increased plasma ghrelin following infliximab in Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009E. Z. H. SUNG Summary Background, Ghrelin, a potent orexigenic peptide produced by the stomach, may be affected by circulating inflammatory mediators. Aim, To assess the effect of an anti-TNF, antibody on ghrelin in patients with Crohn's disease (CD). Methods, Fifteen patients with Crohn's receiving infliximab were studied before and 1 week after infusion. Following an overnight fast, blood was sampled before a meal and then every 20 min for 2 h. Total ghrelin and CRP were measured using ELISA. Acylated ghrelin and TNF,, IFN,, IL-1, and IL-6 were measured with bioplex. Harvey Bradshaw Activity Index was assessed. Results, Median (95% CI) 2-h integrated plasma total ghrelin increased from 162 (99,311) before infliximab to 200 (128,387) pg/mL h, (P = 0.02) after. Following infliximab, 20 min postmeal, median acylated ghrelin decreased from 50.3 (24,64) to 38.6 (26,82) pg/mL, (P = 0.04) thus reverting to a traditional meal related ghrelin curve. Median (range) disease activity decreased from 5 (2,28) before to 3 (0,22), (P = 0.0001) and Median (95% CI) TNF, decreased from 2.8 (1.89,4.48) to 1.31 (0.73,2.06) pg/mL (P = 0.002). Conclusions, Infliximab increases circulating total ghrelin by 25% in CD and restores the postprandial response of acylated ghrelin to food intake. Acylated and de-sacyl ghrelin remain unchanged, suggesting that an alternate isoform could be affected by infliximab. [source] Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humansNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2010Y. Falkén Abstract Background, Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. Methods, Ghrelin (15 pmol kg,1 min,1) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results, The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences, The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders. [source] Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphate-induced colitis in miceNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2009B. De Smet Abstract, Ghrelin is an important orexigenic peptide that not only exerts gastroprokinetic but also immunoregulatory effects. This study aimed to assess the role of endogenous and exogenous ghrelin in the pathogenesis of colitis and in the disturbances of gastric emptying and colonic contractility during this process. Dextran sodium sulphate colitis was induced for 5 days in (i) ghrelin+/+ and ghrelin,/, mice and clinical and histological parameters were monitored at days 5, 10 and 26 and (ii) in Naval Medical Research Institute non-inbred Swiss (NMRI) mice treated with ghrelin (100 nmol kg,1) twice daily for 5 or 10 days. Neural contractility changes were measured in colonic smooth muscle strips, whereas gastric emptying was measured with the 14C octanoic acid breath test. Inflammation increased ghrelin plasma levels. Body weight loss, histological damage, myeloperoxidase activity and IL-1, levels were attenuated in ghrelin,/, mice. Whereas absence of ghrelin did not affect changes in colonic contractility, gastric emptying in the acute phase was accelerated in ghrelin+/+ but not in ghrelin,/, mice. In agreement with the studies in ghrelin knockout mice, 10 days treatment of NMRI mice with exogenous ghrelin enhanced the clinical disease activity and promoted infiltration of neutrophils and colonic IL-1, levels. Unexpectedly, ghrelin treatment decreased excitatory and inhibitory neural responses in the colon of healthy but not of inflamed NMRI mice. Endogenous ghrelin enhances the course of the inflammatory process and is involved in the disturbances of gastric emptying associated with colitis. Treatment with exogenous ghrelin aggravates colitis, thereby limiting the potential therapeutic properties of ghrelin during intestinal inflammation. [source] Obestatin , a ghrelin-associated peptide that does not hold its promise to suppress food intake and motilityNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2007G. Gourcerol Abstract, Ghrelin is a gut peptide well established to induce prokinetic and appetite stimulatory actions. Obestatin is a novel 23-amino acid peptide derived from the processing of the ghrelin gene. The peptide name was in keeping with its initially reported actions to suppress food intake and digestive motility and to antagonize ghrelin's stimulatory effect through interaction with the orphan GPR-39 receptor. However, subsequently, these findings have been questioned because obestatin actions to reduce food intake and to inhibit gastrointestinal (GI) motility in vivo and in vitro have not been reproduced by several groups. Furthermore, while GPR-39 appears to be involved in gut motor functions, convergent reports showed that obestatin is not the cognate ligand for this receptor. In light of recent controversy over the effects of obestatin, the present findings from De Smet et al. provides additional evidence that obestatin does not influence food intake and GI motility in vivo and in vitro. Taken together, existing reports curtail the initial promise that obestatin is a new regulator of appetite and digestive motility. Therefore, it is proposed to rename obestatin as ghrelin-associated peptide. [source] Ghrelin and leptin modulate immunity and liver function in overweight childrenPEDIATRICS INTERNATIONAL, Issue 1 2009Yuki Okamatsu Abstract Background:, The rising prevalence of obesity represents a growing worldwide public health problem. Interactions of adipocytokines and low-grade systemic inflammation presently are considered important in the development of obesity, as well as associated chronic disease including bronchial asthma, obesity-related liver disease and type 2 diabetes mellitus. The purpose of the present study was to investigate metabolic, hormonal, immunologic and inflammatory factors in overweight children and to further clarify possible immunomodulatory effects of obesity-related hormones and cytokines. Methods:, Forty-nine prepubertal overweight children and 49 age-matched controls of normal weight without underlying disease were enrolled. Levels of plasma ghrelin and serum leptin, cytokines (interleukin [IL]-4, IL-10, IL-12, 1L-13), C-reactive protein, immunoglobulin, and insulin were measured, and liver function tests were done to better understand their status in the setting of obesity. Results:, Overweight subjects had significantly higher measures of adiposity (body mass indexI, % body fat) and had significantly higher serum levels of IgG, IgA and IgE than non-obese children (P = 0.038, 0.0043, 0.0034, respectively); the opposite was true for IgM (P = 0.025). The incidence of presumed non-alcoholic fatty liver disease was 28.6% in overweight children. In overweight children, serum leptin levels were associated with liver function index (aspartate aminotransferase/alanine aminotransferase ratio) and serum insulin levels. Some elevated immunoglobulin levels significantly correlated with plasma ghrelin levels and liver function index. Conclusions:, It is possible that appetite-regulating hormones modulate both humoral immunity and liver function. Further studies with a larger number of subjects are needed to clarify the precise mechanisms of this association. [source] Serum ghrelin levels in children with primary protein,energy malnutritionPEDIATRICS INTERNATIONAL, Issue 4 2008Sevin Altinkaynak Abstract Background: Ghrelin, an appetite-stimulating peptide, increases in cachectic conditions. It probably reflects peripheral nutritional status and influences nutrient intake and growth. The aim of the present study was to determine serum ghrelin levels in children with primary protein,energy malnutrition (PEM) and to find if any correlation exists between serum ghrelin levels and the clinical presentation of those patients. Methods: Twenty-eight children with primary PEM and 10 healthy children were included. Serum fasting ghrelin levels were measured using radioimmunoassay. Results: Mean serum ghrelin level of healthy children and those with PEM were 107.7 ± 40.1 pg/mL and 141.6 ± 123.8 pg/mL, respectively (P < 0.001). Ghrelin levels were independent of age and sex (P > 0.05). Ghrelin was negatively correlated with body mass index in healthy children (P < 0.01), but not in those with PEM (P > 0.05). Mean serum ghrelin level of children with moderate malnutrition was higher than that of children with severe malnutrition (199.2 ± 154.1 pg/mL vs 98.4 ± 74.3 pg/mL, P < 0.05). Mean serum ghrelin levels of patients with kwashiorkor, marasmic kwashiorkor, and marasmus were 127.9 ± 97.8 pg/mL, 138.7 ± 95.8 pg/mL, and 162.3 ± 185.0 pg/mL, respectively (P > 0.05). Conclusion: Serum ghrelin level is higher in patients with PEM, especially in those with marasmus, compared to healthy children. Although this observation suggests that ghrelin helps to fight malnutrition in children, it is obvious that further studies are needed to clarify the exact pathogenetic mechanism regarding this condition. [source] Effect of food restriction on ghrelin in adult male rats and its relation to male reproductive hormonesANDROLOGIA, Issue 2 2010H. M. Abou Heif Summary Ghrelin is an endogenous ligand for growth hormone secretagogue (GHS) receptor (GHS-R). It has recently emerged as an orexigenic food intake controlling signal acting upon hypothalamic centres. To study the effect of food restriction on ghrelin level and its relation to male reproductive hormones, 32 adult male albino rats divided into two groups: Group I (8 rats as a control group) fed ad libitum for 21 days and 24 rats as Group II (food-restricted group) fed 30% of ad libitum intake of food consumed by the control group. Rats were weighed every 3 days. Group II rats were further subdivided into three subgroups: IIa, IIb and IIc that were killed at days 8, 16 and 21 from the start of food restriction respectively. Ghrelin level was assayed by ELISA technique in serum samples and tissue homogenates prepared from the stomach and hypothalamus. In addition, male reproductive hormones: testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assayed in serum by chemiluminescence. Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced a significant increase of serum ghrelin and a significant decrease of both gastric and hypothalamic ghrelin in group II when compared with group I. The changes in ghrelin level varied with the duration of food restriction. Significant inverse correlation was found between serum ghrelin and each of gastric and hypothalamic ghrelin in group II. A significant decrease of testosterone, FSH and LH were found in food restricted rats compared with controls. The decrease was significantly related to the duration of food restriction. Significant inverse correlation was detected between serum ghrelin and each of the male reproductive hormones in food restricted group II rats. Thus ghrelin could be one of the hormones responsible for the suppression of male reproductive axis in case of negative energy balance. [source] Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelinANDROLOGIA, Issue 6 2009A. Kheradmand Summary Ghrelin has recently been reported to exert beneficial effects on various oxidative stresses as a result of its antioxidant properties. Therefore, we designed this study to explore the probable antioxidative effects of this peptide in the testis. Twenty-eight male adult Wistar rats were divided into equal control and treatment groups. In the treatment group, 1 nmol of ghrelin was administered as subcutaneous injection for 10 consecutive days or vehicle (physiological saline) to the control rats. The control and treated rats were killed on days 6 and 10 after beginning of ghrelin injection (n = 7 from each group on each day). The testes were taken and measured for antioxidant enzyme activity and malondialdehyde (MDA) content. Glutathione peroxidase activity significantly increased on day 10 in the treated animals compared with the control group (P < 0.05). Although the mean activity of glutathione peroxidase was greater on day 6 in the ghrelin-treated group than in the control animals, it was not statistically significant. There were no significant differences in superoxide dismutase and catalase activities between the groups. However, MDA level decreased by ghrelin treatment on day 10 compared with the control rats (P < 0.05). The results of this study indicate for the first time novel evidences for antioxidant properties of ghrelin in the rat testis. [source] A Genetic Study of the Ghrelin and Growth Hormone Secretagogue Receptor (GHSR) Genes and StatureANNALS OF HUMAN GENETICS, Issue 1 2009M. Gueorguiev Summary Growth and nutrition are interrelated and influenced by multiple genetic and environmental factors. We studied whether common variants in ghrelin and ghrelin receptor (GHSR) genes could play a role in stature variation in the general population and in families ascertained for obesity. Selected tagging SNPs in the ghrelin and GHSR genes were genotyped in 263 Caucasian families recruited for childhood obesity (1,275 subjects), and in 287 families from a general population (1,072 subjects). We performed familial testing for associations in the entire population and in a sub-set of the samples selected for a case-control study. In the case-control study for height (cases were selected from the obese cohort with mean ZH = 3.17 ± 0.15 confidence interval (CI) versus controls with mean ZH 0.14 ± 0.09), we found an association with a 2 base-pair intronic deletion in the GHSR gene (rs10618418) (p = 0.006, odds ratio (OR) 1.86, 95% CI [1.26;2.74] under additive model), although when adjusting for BMI, the association disappeared (p = 0.06). Individuals carrying no deletion or who were heterozygous were significantly more frequent among the tall obese population (52% vs. 36% in controls, p = 0.007, OR 1.97, 95%CI [1.22;3.18]). However, the association was not maintained after correcting for multiple testing. Familial association testing of the ghrelin and GHSR genes and their interaction testing failed to show that any combination of SNPs had any significant effect. Thus, our results suggest that common variants of the ghrelin and GHSR genes are not major contributors to height variation in a French population. [source] 2127: Ghrelin concentration in the aqueous humour and plasma in open angle glaucoma patientsACTA OPHTHALMOLOGICA, Issue 2010A KATSANOS Purpose Ghrelin is a peptide hormone that exerts metabolic and smooth muscle-relaxant effects in ocular tissues. The aim of this study was to compare aqueous humor and plasma levels of ghrelin in patients with open angle glaucoma (OAG) and controls. Methods Twenty four OAG, including 7 pseudoexfoliation (PXG) and 17 primary open-angle glaucoma (POAG) patients, and 30 controls were included. All participants were patients scheduled for cataract or glaucoma surgery. Patients with other concomitant ocular disease, previous ocular surgery or diabetes were excluded. Blood samples were collected before cataract surgery. Aqueous humor was aspirated from the anterior chamber through a paracentesis with a 27 G needle under sterile conditions. Ghrelin levels in both samples were measured quantitatively with commercially available Radioimmunoassay (RIA) kits. Results Mean±SD age was 71.0±9.3 and 69.6±6.6 years in the OAG and control groups, respectively (p=0.6). Plasma levels of ghrelin were 495.6±157.7 pg/ml in the OAG and 482.2±125.4 pg/ml in the control group, respectively (Mann-Whitney test, p=0.9). Aqueous humor levels of ghrelin were 85.5±15.4 pg/ml and 123.4 ±25.5 pg/ml in the OAG and control groups, respectively (Mann-Whitney test, p<0.01). The ratio of plasma/aqueous concentration in ghrelin was higher in the OAG versus the control group (5.82± 1.94 versus 4.00±1.04, Mann-Whitney test, p<0.01). There was no difference neither in plasma nor in aqueous humor levels of ghrelin between POAG and PXG patients (p>0.5). Conclusion Aqueous humor levels of ghrelin were significantly lower in OAG patients. This difference may manifest a role of ghrelin in the disease process or a consequence of antiglaucoma treatment. [source] Bone metabolism markers and ghrelin in boys at different stages of sexual maturityACTA PAEDIATRICA, Issue 5 2009Jaak Jürimäe Abstract Aim: To examine the relationship of the markers of bone formation (procollagen type I N-terminal propeptide [PINP]) and bone resorption (type I carboxyterminal telopeptide [ICTP]) with bone mineral content (BMC), bone mineral density (BMD), ghrelin and testosterone in boys during puberty. Methods: Sixty boys were divided in three groups (20 boys in each) based on the pubertal stage (G1, I; G2,G3, II; G4,G5, III). Fasting PINP, ICTP, ghrelin and testosterone were measured. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD) and BMC were measured by DXA. Results: PINP and ICTP values peaked at the beginning of puberty (Group II). Ghrelin was lower in Groups II and III compared to less mature boys. PINP and ICTP correlated with each other and were associated with lumbar BMAD in total group of boys. Relationships of PINP and ICTP with total BMD, total BMC and lumbar spine BMD in Group I were observed. PINP and ICTP were also correlated with testosterone in Group II and with lumbar spine BMAD in Group III. Conclusion: These data suggest that testosterone stimulates PINP and ICTP in early puberty, while ghrelin has no direct influence on bone turnover markers in boys at different stages of puberty. [source] Long-term effect of ghrelin on nutritional status and functional capacity in the elderly: a population-based cohort studyCLINICAL ENDOCRINOLOGY, Issue 1 2010Mateu Serra-Prat Summary Background, Ghrelin stimulates GH release and hunger at a central level. Ghrelin declines with age, which may be partially responsible for functional impairment and frailty. Objective, To describe the evolution of nutritional status and functional capacity of noninstitutionalized old people over a 2-year period, as well as to evaluate the relationship between ghrelin and long-term changes in nutritional and functional status in this population. Design, A population-based cohort study was designed in which 313 randomly selected persons, 70 years old or older, were followed for a 2-year period. Functional (Barthel and Guralnik scores and hand grip) and nutritional (MNA-SF, weight and BMI) assessments were performed during basal and 2-year follow-up visits. Ghrelin and hormonal components of the gonadotrophe and somatotrophe axis were determined. Results, During follow-up, 13% of men and 20% of women showed a >5% weight loss, and the nutritional status of 18% of men and 39% of women deteriorated. Men lost 12·1% and women lost 9·7% of their initial hand grip strength. In men, low basal ghrelin levels were associated with higher weight loss and poorer hand grip but not with the MNA-SF measure, whereas in women, low basal ghrelin levels were associated with a decline in nutritional status (MNA-SF) but not with weight loss and hand grip decline. Conclusion, Low ghrelin levels have been related to worsening nutritional status in a 2-year follow-up period in people 70 years old or older, which suggests this hormone could become a useful therapeutic target in the elderly. [source] Perioperative plasma active and total ghrelin levels are reduced in acromegaly when compared with in nonfunctioning pituitary tumours even after normalization of serum GHCLINICAL ENDOCRINOLOGY, Issue 1 2007Takakazu Kawamata Summary Objective, Ghrelin is a novel gastric peptide known to stimulate GH secretion, but the relationship between ghrelin and the GH-insulin-like growth factor (IGF)-1 axis in GH excess or deficiency is poorly understood. This study investigated dysregulation of ghrelin secretion in acromegaly and its short-term postoperative recovery. Methods, A prospective study was conducted on eight patients who underwent complete transsphenoidal resection of GH-producing pituitary adenomas (acromegaly group) and 22 for endocrinologically nonfunctioning pituitary tumours (control group). Active and total plasma ghrelin levels were measured serially before and after surgery. Results, Preoperative active and total plasma ghrelin concentrations (mean ± SD; fmol/ml) were significantly reduced in acromegalic patients when compared with those in the controls (9·6 ± 4·3 and 157·4 ± 65·6 vs. 21·8 ± 13·0 and 267·1 ± 111·4; P = 0·023 and P = 0·021, respectively). Both levels were still significantly suppressed on postoperative Day 7 in the acromegaly group when compared with those in the control group (11·7 ± 4·3 and 197·8 ± 68·9 vs. 22·5 ± 12·6 and 302·7 ± 100·0; P = 0·038 and P = 0·018, respectively). The ratios of active to total ghrelin were not significantly different between the two groups before and after operation. In acromegalic patients, active and total ghrelin levels remained significantly suppressed even after normalization of serum GH levels. Conclusions, The putative negative feedback mechanism of GH on ghrelin secretion may in part account for the low ghrelin levels observed in acromegalic patients, and the mechanism may persist even after normalization of serum GH. [source] Ghrelin does not regulate the GH response to insulin-induced hypoglycaemia in children but could be involved in the regulation of cortisol secretionCLINICAL ENDOCRINOLOGY, Issue 1 2007J. Huber Summary Objective, Ghrelin activates the growth hormone secretagogue receptor GHS-R. It strongly stimulates GH secretion and has a role in energy homeostasis. The relationship between plasma ghrelin and cortisol levels during insulin-induced hypoglycaemia in prepubertal and pubertal children has not yet been investigated. The aim of the present study was to establish whether insulin-induced hypoglycaemia stimulates ghrelin secretion and whether changes in ghrelin concentrations are related to changes in GH and cortisol in children. Design and patients, We studied a group of 20 children and adolescents (five girls, 15 boys, mean age 10·8 ± 3·7 years) undergoing insulin tolerance tests (ITTs) for clinical investigation of GH deficiency. Measurements, Stimulation tests were performed to investigate the relationship between ghrelin, GH, cortisol and glucose levels according to age and pubertal stage by determining the ghrelin profiles during insulin-induced hypoglycaemia (at 0, 60 and 120 min). Results, Ghrelin was significantly and inversely related to body weight, height, body mass index (BMI) and age of children (P < 0·05). Significant changes in ghrelin levels (P = 0·00013) were found after the insulin bolus, with a decline at 60 min and an increase to baseline values at 120 min. Changes in cortisol levels were negatively correlated with changes in ghrelin at 60 min (r = ,0·59, P = 0·004) and at 120 min (r = ,0·605, P = 0·003). Conclusions, This study shows that ghrelin might not regulate the GH response to insulin-induced hypoglycaemia in prepubertal and pubertal children. A role for ghrelin in the regulation of cortisol secretion can be hypothesized concerning the negative correlation between changes in ghrelin and cortisol. Furthermore, the results imply that ghrelin secretion is age dependent and is a function of growth. [source] Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysisCLINICAL ENDOCRINOLOGY, Issue 1 2006Pedro Iglesias Summary Background, ,Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated. Objective, ,Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis). Patients and measurements, ,We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61·2 ± 1·8 years) and PD groups (n = 38, 21 men, age 54·4 ± 1·7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects. Results, ,Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 ± 787 vs 9280 ± 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 ± 216 pg/ml, P < 0·0001). Men and women showed similar serum ghrelin levels in both HD (9845·9 ± 1071 vs 9085 ± 1194 pg/ml) and PD patients (3214 ± 297 vs 3250 ± 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0·46, P < 0·05) and PD (r = 0·53, P < 0·001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found. Conclusions, ,These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients. [source] Ghrelin: more than a natural GH secretagogue and/or an orexigenic factorCLINICAL ENDOCRINOLOGY, Issue 1 2005E. Ghigo Summary Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a). Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also nonendocrine actions that are explained by the widespread distribution of ghrelin and GHS-R expression. The likely existence of GHS-R subtypes and evidence that the neuroendocrine actions, but not all the other actions, of ghrelin depend on its acylation in serine-3 revealed a system whose complexity had not been completely explored by studying synthetic GHS. Ghrelin secretion is mainly regulated by metabolic signals and, in turn, the modulatory action of ghrelin on the control of food intake and energy metabolism seems to be among its most important biological actions. However, according to a recent study, ghrelin-null mice are neither anorectics nor dwarfs and this evidence clearly depicts a remarkable difference from leptin null mice. Nevertheless, the original and fascinating story of ghrelin, as well as its potential pathophysiological implications in endocrinology and internal medicine, is not definitively cancelled by these data as GHS-R1a null aged mice show significant alterations in body composition and growth, in glucose metabolism, cardiac function and contextual memory. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, there are several open questions awaiting an answer. How many ghrelin receptor subtypes exist? Is ghrelin ,the' or just ,a' GHS-R ligand? That is, are there other natural GHS-R ligands? Is there a functional balance between acylated and unacylated ghrelin forms, potentially with different actions? Within the next few years suitable answers to these questions will probably be found, making it possible to gain a better knowledge of ghrelin's potential clinical perspectives. [source] Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adultsCLINICAL ENDOCRINOLOGY, Issue 1 2004Claudia Giavoli Summary objective, To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. patients and methods, Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean ± SD: 0·3 ± 0·1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0·025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. results, Group,A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31·4 ± 2·5 vs. 26·4 ± 1·3, P < 0·05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193·9 ± 27·1 vs. 298·1 ± 32·5 pmol/l, respectively, P = 0·02), while ApN levels were similar (10·2 ± 1·1 and 9 ± 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193·9 ± 27·1 to 232·4 ± 26·3 pmol/l (P < 0·01) and from 8·6 ± 0·8 to 10·3 ± 1·1 mg/l (P < 0·05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. conclusion, GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release. [source] Endocrine responses to ghrelin in adult patients with isolated childhood-onset growth hormone deficiencyCLINICAL ENDOCRINOLOGY, Issue 6 2002Gianluca Aimaretti Summary objective Ghrelin, a 28 amino acid acylated peptide, is a natural ligand of the GH secretagogues (GHS) receptor (GHS-R), which is specific for synthetic GHS. Similar to synthetic GHS, ghrelin strongly stimulates GH secretion but also displays significant stimulatory effects on lactotroph and corticotroph secretion. It has been hypothesized that isolated GH deficiency (GHD) could reflect hypothalamic impairment that would theoretically involve defect in ghrelin activity. patients In the present study, we verified the effects of ghrelin (1 µg/kg i.v.) on GH, PRL, ACTH and cortisol levels in adult patients with isolated severe GHD [five males and one female, age (mean ± SEM) 24·7 ± 2·6 years, BMI 25·7 ± 2·7 kg/m2]. In all patients, the GH response to insulin-induced hypoglycaemia (ITT, 0·1 IU regular insulin i.v.) and GH releasing hormone (GHRH) (1 µg/kg i.v.) + arginine (ARG, 0·5 g/kg i.v.) was also studied. The hormonal responses in GHD were compared with those in age-matched normal subjects (NS, seven males, age 28·6 ± 2·9 years, BMI 22·1 ± 0·8 kg/m2). results IGF-I levels in GHD were markedly lower than in NS (69·8 ± 11·3 vs. 167·9 ± 19·2 µg/l, P < 0·003). Ghrelin administration induced significant increase in GH, PRL, ACTH and cortisol levels in all GHD. In GHD, the GH response to ghrelin was higher (P < 0·05) than that to GHRH + ARG, which, in turn, was higher (P < 0·05) than that to ITT (9·2 ± 4·1 vs. 5·3 ± 1·7 vs. 1·4 ± 0·4 µg/l). These GH (1 µg/l = 2 mU/l) responses in GHD were markedly lower (P < 0·0001) than those in NS (ghrelin vs. GHRH + ARG vs. ITT 92·1 ± 16·7 vs. 65·3 ± 8·9 vs. 17·7 ± 3·5 µg/l). In GHD, the highest individual peak GH response to ghrelin was markedly lower than the lowest peak GH response in NS (28·5 vs. 42·9 µg/l). GHD and NS showed overlapping PRL (1 µg/l = 32 mU/l) (10·0 ± 1·4 vs. 14·9 ± 2·2 µg/l), ACTH (22·3 ± 5·3 vs. 18·7 ± 4·6 pmol/l) and cortisol responses (598·1 ± 52·4 vs. 486·9 ± 38·9 nmol/l). conclusions This study shows that ghrelin is one of the most powerful provocative stimuli of GH secretion, even in those patients with isolated severe GHD. In this condition, however, the somatotroph response is markedly reduced while the lactotroph and corticotroph responsiveness to ghrelin is fully preserved, indicating that this endocrine activity is fully independent of mechanisms underlying the GH-releasing effect. These results do not support the hypothesis that ghrelin deficiency is a major cause of isolated GH deficiency but suggest that ghrelin might represent a reliable provocative test to evaluate the maximal GH secretory capacity provided that appropriate cut-off limits are assumed. [source] | ||||||||||||||||||||||||||||||||||