Background and Objective: Ghrelin is a novel gastric peptide which stimulates GH secretion and has been demonstrated to have orexigenic and adipogenic properties. Insulin is a physiological and dynamic modulator of plasma ghrelin, and insulinemia possibly mediates the effect of the nutritional state on the plasma concentrations of ghrelin in adults. No data on the regulation of GH secretion by ghrelin have so far been reported, nor has the possible influence of hypoglycemia on the plasma ghrelin levels in children been reported. Methods: Provocative studies were performed using a variety of stimuli, including insulin-induced hypoglycemia, and glucagon, arginine and L-dopa loading. We studied a group of 27 children with short stature being investigated for GH deficiency (10 F, 17 M; age 4–14 years; height SDS –0.92 to –3.27); the subjects were instructed to fast overnight, and the following morning, the relationships among the plasma ghrelin, GH and glucose levels were investigated by determining the plasma ghrelin profiles during those provocative tests. Using a new method for determining the two types of ghrelin, samples were obtained for determination of the plasma ghrelin, serum glucose and serum GH levels after the administration of the aforementioned stimulating agents. Results: All the four stimuli caused a significant decrease in the circulating C- and N-ghrelin levels with a nadir at +30 min, with the exception of the N-ghrelin level following the L-dopa loading. During the same period, the plasma GH level increased following insulin, arginine and L-dopa loading, and the plasma glucose level increased significantly following glucagon loading. In the arginine and L-dopa load connected, a significant correlation was observed between the 30-min change in the serum GH level and the 30-min change in the plasma C-ghrelin level. In the multiple regression analysis to explain the 30-min change in the plasma level of C-ghrelin, the baseline plasma level of C-ghrelin (basal), height and % overweight were the only three significant parameters, accounting for 85.2% of the variance. Conclusion: This study demonstrated that the inverse relation between the circulating GH and ghrelin levels may indicate the existence of a feedback loop, and also lends support to the assumption of a GH-independent relationship between plasma ghrelin and glucose levels. These observations constitute further evidence to suggest that peripheral ghrelin is a direct growth-promoting hormone.

Bellone S, Castellino N, Broglio F, Rapa A, Vivenza D, Radetti G, Bellone J, Gottero C, Ghigo E, Bona G: Ghrelin secretion in childhood is refractory to the inhibitory effect of feeding. J Clin Endocrinol Metab 2004;89:1662–1665.
Tanner JM, Whitehouse RH: Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51:170–179.
Zachmann M, Prader A, Kind HP, Hafliger H, Budliger H: Testicular volume during adolescence: cross-sectional and longitudinal studies. Helv Paediatr Acta.1974;29:61–72.
Suwa S, Tachibana K: Standard growth charts for height and weight of Japanese children from birth to 17 years based on a cross-sectional survey of national data. Clin Pediatr Endocrinol 1993;82:87–97.
Yamazaki K, Matsuoka H, Kawanobe S, Fujita Y, Murata M: Evaluation of standard body weight by sex, age and height – on the basis of 1990 school year data (in Japanese). J Jpn Pediatri Soc 1993;97:1203–1333.
Ashizawa K, Asami T, Anzo M, Matsuo N, Matsuoka H, Murata M, Ohtsuki F, Satoh M, Tanaka T, Tatara H, Tsukagoshi K: Standard RUS skeletal maturation of Tokyo children. Ann Hum Biol 1996;23:457–469.
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656–660.
Hosoda H, Kojima M, Matsuo H, Kangawa K: Ghrelin and des-acyl ghrelin: Two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 2000;279:909–913.
Saad MF, Bernaba B, Hwu CM, Jinagouda S, Fahmi S, Kogosov E, Boyadjian R: Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 2002;87:3997–4000.
Broglio F, Prodam F, Gottero C, Destefanis S, Me E, Riganti F, Giordano R, Picu A, Balbo M, van der Lely AJ, Ghigo E, Arvat E: Ghrelin does not mediate the somatotroph and corticotroph responses to the stimulatory effect of glucagon or insulin induced hypoglycaemia in humans. Clin Endocrinol (Oxf) 2004;60:699–704.
Broglio F, Gottero C ,Prodam F, Destefanis S, Me E, Gauna C, Me E, Riganti F, Vivenza D, Rapa A, Martina V, Arvat E, Bona G, van der Lely AJ ,Ghigo E: Ghrelin secretion is inhibited by glucose load and insulin-induced hypoglycaemia but unaffected by glucagon and arginine in humans. Clin Endocrinol (Oxf) 2004;61:503–509.
Hirsh D, Heinrichs C, Leenders B, Wong A, Cummings D, Chanoine J: Ghrelin is suppressed by glucagon and does not mediate glucagons-related growth hormone release. Horm Res 2005;63:111–118.
Stock S, Leichner P, Wong ACK, Ghatei MA, Kieffer TJ, Bloom SR, Chanoine JP: Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents. J Clin Endocrinol Metab 2005;90:2161–2168.
Ikezaki A, Hosoda H, Ito K, Iwama S, Miura N, Matsuoka H, Kondo C, Kojima M, Kangawa K, Sugihara S: Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes 2002;51:3401–3411.
Valcabi R: Oral glucose tolerance test: an inhibitory or a stimulatory input to growth hormone secretion. J Endocrinol Invest 1996;19:253–255.
Ghizzoni L, Mastorakos G, Vottero A, Ziveri M, Ilias I, Bernasconi S: Spontaneous growth hormone (GH) secretion is not directly affected by ghrelin in either short normal prepubertal children or children with GH neurosecretory dysfunction. J Clin Endocrinol Metab 2004;89:5488–5495.
Janssen J, Toorn FM, Hofland LJ, Koetsveld P, Broglio F, Ghigo E, Lamberts S, Lely A: Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy. Eur J Endocrinol 2001;145:711–716.
Engstrom BE, Burman P, Holdstock C, Karlsson FA: Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients. J Clin Endocrinol Metab 2003;88:5193–5198.
Whatmore AJ, Hall CM, Jones J, Westwood M, Clayton PE: Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol (Oxf) 2003;59:649–654.
Bellone S, Rapa A, Vivenza D, Castellino N, Petri A, Bellone J, Me E, Broglio F, Prodam F, Ghigo E, Bona G: Circulating ghrelin levels as function of gender, pubertal status and adiposity in childhood. J Endocrinol Invest 2002;25:RC13–RC15.
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