Abstract
Ghrelin, the natural ligand of the GH secretagogue (GHS) receptor, was originally isolated from the stomach and detected in several tissues, but a systematic study of its tissue distribution has not been performed. In the present investigation, we evaluated ghrelin gene expression (by RT-PCR technique) and ghrelin protein concentration (by enzyme immunoassay technique) in tissues obtained from control rats as well as in rats subjected to 48-h fasting. The ghrelin gene was expressed in stomach, small intestine, brain, cerebellum, pituitary, heart, pancreas, salivary gland, adrenal, ovary and testis, with maximum expression occurring in the stomach, while no significant expression was detected by standard RT-PCR in liver, lung, kidney and skeletal muscle. Ghrelin protein was detected in stomach, small intestine, brain, cerebellum, pituitary, lung, skeletal muscle pancreas, salivary gland, adrenal, ovary and testis, at concentrations ranging from 0.05 to 1.43 ng/mg of homogenate protein (the highest concentration occurred in the lung, followed by the brain). Ghrelin was not detectable in the heart, liver and kidney. Therefore, gene and protein expression were dissociated. Fasting did not produce significant changes in ghrelin gene expression, while the distribution of ghrelin between different tissues was significantly modified: protein concentration increased in the brain, cerebellum, lung and salivary gland, while it decreased in the stomach.
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Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1 999, 402: 656–6
Date Y, Kojima M, Hosoda H, et al. 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 2000, 141: 4255–61.
Gualillo O, Caminos J, Blanco M, et al. Ghrelin, a novel placental-derived hormone. Endocrinology 2001, 142: 788–94.
Mori K, Yoshimoto A, Takaya K, et al. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett 2000, 486: 213–6.
Korbonits M, Bustin SA, Kojima M, et al. The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab 2001, 86: 881–7.
Shuto Y, Shibasaki T, Otagiri A, et al. Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J Clin Invest 2002, 109: 1429–36.
Cowley MA, Smith RG, Diano S, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003, 37: 649–61.
Frascarelli S, Ghelardoni S, Ronca-Testoni S, Zucchi R. Effect of ghrelin and synthetic growth hormone secretagogues in normal and ischemic rat heart. Basic Res Cardiol. 2004, 43: 294–9.
Ghigo E, Broglio F, Arvat E, Maccario M, Papotti M, Muccioli G. Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol (Oxf) 2005, 62: 1–17.
Lee HM, Wang G, Englander EW, Kojima M, Greeley GH Jr. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 2002, 143: 185–90.
Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001, 50: 1714–9.
Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001, 50: 707–9.
Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000, 407: 908–13.
Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001, 409: 194–8.
Marchesini G, Bianchi G, Lucidi P, Villanova N, Zoli M, De Feo P. Plasma ghrelin concentrations, food intake, and anorexia in liver failure. J Clin Endocrinol Metab 2004, 89: 2136–41.
Sanchez J, Oliver P, Palou A, Pico C. The inhibition of gastric ghrelin production by food intake in rats is dependent on the type of macronutrient. Endocrinology 2004, 145: 5049–55.
Wortley KE, Anderson KD, Garcia K, et al. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci USA 2004, 101: 8227–32.
Beck B, Musse N, Stricker-Krongrad A. Ghrelin, macronutrient intake and dietary preferences in long-evans rats. Biochem Biophys Res Commun 2002, 292: 1031–5.
Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002, 87: 2988.
Long C. Biochemists Handbook. London: E&FN Spon LTd. 1961.
Ariyasu H, Takaya K, Tagami T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001, 86: 4753–8.
Torsello A, Scibona B, Leo G, et al. Ontogeny and tissue-specific regulation of ghrelin mRNA expression suggest that ghrelin is primarily involved in the control of extraendocrine functions in the rat. Neuroendocrinology 2003, 77: 91 -9.
Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000, 141: 4325–8.
Akamizu T, Takaya K, Irako T, et al. Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects. Eur J Endocrinol 2004, 150: 447–55.
Nagaya N, Kojima M, Uematsu M, et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 2001, 280: R1483–7.
Tigno XT, Selaru IK, Angeloni SV, Hansen BC. Is microvascular flow rate related to ghrelin, leptin and adiponectin levels? Clin Hemorheol Microcirc 2003, 29: 409–16.
Muccioli G, Papotti M, Locatelli V, Ghigo E, Deghenghi R. Binding of 125I-labeled ghrelin to membranes from human hypothalamus and pituitary gland. J Endocrinol Invest 2001, 24: RC7–9.
Talebizadeh Z, Kibiryeva N, Bittel DC, Butler MG. Ghrelin, peptide YY and their receptors: Gene expression in brain from subjects with and without Prader-Willi syndrome. Int J Mol Med 2005, 15: 707–11.
Rindi A, Torsello A, Locatelli V, Solcia E. Ghrelin expression and actions: a novel peptide for an old cell type on the diffuse endocrine system. Exp Biol Med 2004, 229: 1007–16.
Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin — a hormone with multiple functions. Front Neuroen-docrinol 2004, 25: 27–68.
Volante M, Fulcheri E, Allia E, Cerrato M, Pucci A, Papotti M. Ghrelin expression in fetal, infant, and adult human lung. J Histochem Cytochem. 2002, 50: 1013–21.
Angeloni SV, Glynn N, Ambrosini G, et al. Characterization of the rhesus monkey ghrelin gene and factors influencing ghrelin gene expression and fasting plasma levels. Endocrinology. 2004, 145: 2197–205.
Ariyasu H, Takaya K, Iwakura H. Transgenic mice overexpressing des-acyl ghrelin show small phenotype. Endocrinology 2004, 146: 355–64.
Halmos G, Schally AV, Comaru-Schally AM, Nagy A, Irimpen A. Absence of binding of targeted analogs of somatostatin carrying cytotoxic radicals or radionuclides to growth hormone secretagogue receptors on human myocardium. Life Sci 2003, 72: 2669–74.
Papotti M, Ghe C, Cassoni P, et al. Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 2000, 85: 3803–7.
Patterson M, Murphy KG, le Roux CW, Ghatei MA, Bloom SR. Characterisation of Ghrelin-like immunoreactivity in human plasma. J Clin Endocrinol Metab 2005, 90: 2205–11.
Toshinai K, Mondal MS, Nakazato M, et al. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 2001, 281: 1220–5.
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Ghelardoni, S., Carnicelli, V., Frascarelli, S. et al. Ghrelin tissue distribution: Comparison between gene and protein expression. J Endocrinol Invest 29, 115–121 (2006). https://doi.org/10.1007/BF03344083
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DOI: https://doi.org/10.1007/BF03344083