Ghrelin in neuroendocrine organs and tumours

Pituitary - 2007
Chrysanthia A. Leontiou1, Gian Gabriele Franchi1,2, Márta Korbonits1
1Department of Endocrinology, William Harvey Research Institute, Barts and the London Medical School, London, UK
2Endocrinology Unit, “Vita-Salute” San Raffaele University Hospital, Milan, Italy

Tóm tắt

Từ khóa


Tài liệu tham khảo

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660

Korbonits M, Kojima M, Kangawa K, Grossman AB (2001) Presence of ghrelin in normal and adenomatous human pituitary. Endocrine 14:101–104

Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, Inagaki C (2001) GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab 86:4284–4291

Gnanapavan S, Kola B, Bustin SA et al (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87:2988

Korbonits M, Bustin SA, Kojima M et al (2001) The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab 86:881–887

Iwakura H, Hosoda K, Doi R et al (2002) Ghrelin expression in islet cell tumors: augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I. J Clin Endocrinol Metab 87:4885–4888

Cassoni P, Papotti M, Ghe C et al (2001) Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab 86:1738–1745

Kanamoto N, Akamizu T, Hosoda H et al (2001) Substantial production of ghrelin by a human medullary thyroid carcinoma cell line. J Clin Endocrinol Metab 86:4984–4990

Volante M, Allia E, Fulcheri E et al (2003) Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects on tumor growth. Am J Pathol 162:645–654

Morpurgo PS, Cappiello V, Verga U et al (2005) Ghrelin in human medullary thyroid carcinomas. Clin Endocrinol (Oxf) 63:437–441

Raghay K, Garcia-Caballero T, Nogueiras R et al (2006) Ghrelin localization in rat and human thyroid and parathyroid glands and tumours. Histochem Cell Biol 125:239–246

Van Der Lely AJ, Tschop M, Heiman ML, Ghigo E (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25:426–457

Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (2004) Ghrelin—a hormone with multiple functions. Front Neuroendocrinol 25:27–68

Momany FA, Bowers CY, Reynolds GA, Chang D, Hong A, Newlander K (1981) Design, synthesis and biological activity of peptides which release growth hormone, in vitro. Endocrinology 108:31–39

Smith RG, Van der Ploeg LHT, Howard AD et al (1997) Peptidomimetic regulation of growth hormone secretion. Endocrine Rev 18:621–645

Howard AD, Feighner SD, Cully DF et al (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974–977

Elphick MR, Egertova M (2001) The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci 356:381–408

Olson GA, Olson RD, Kastin AJ, Coy DH (1979) Endogenous opiates: through 1978. Neurosci Biobehav Rev 3:285–299

Kojima M, Hosoda H, Matsuo H, Kangawa K (2001) Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab 12:118–122

Okada K, Ishii S, Minami S, Sugihara H, Shibasaki T, Wakabayashi I (1996) Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats. Endocrinology 137:5155–5158

Locke W, Kirgis HD, Bowers CY, Abdoh AA (1995) Intracerebroventricular growth-hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats. Life Sci 56:1347–1352

Tschop M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407:908–913

Asakawa A, Inui A, Kaga T et al (2001) Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 120:337–345

Date Y, Murakami N, Kojima M et al (2000) Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats. Biochem Biophys Res Commun 275:477–480

Wren AM, Small CJ, Ward HL et al (2000) The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141:4325–4328

Takaya K, Ariyasu H, Kanamoto N et al (2000) Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab 85:4908–4911

Nagaya N, Miyatake K, Uematsu M et al (2001) Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 86:5854–5859

Tritos NA, Kokkotou EG (2006) The physiology and potential clinical applications of ghrelin, a novel peptide hormone. Mayo Clin Proc 81:653–660

Mano-Otagiri A, Nemoto T, Sekino A et al (2006) Growth hormone-releasing hormone (GHRH) neurons in the arcuate nucleus (Arc) of the hypothalamus are decreased in transgenic rats whose expression of ghrelin receptor is attenuated: evidence that ghrelin receptor is involved in the up-regulation of GHRH expression in the Arc. Endocrinology 149:4093–4103

Olszewski PK, Grace MK, Billington CJ, Levine AS (2003) Hypothalamic paraventricular injections of ghrelin: effect on feeding and c-Fos immunoreactivity. Peptides 24:919–923

Cowley MA, Smith RG, Diano S et al (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37:649–661

Shrestha YB, Wickwire K, Giraudo SQ (2006) Role of AgRP on ghrelin-induced feeding in the hypothalamic paraventricular nucleus. Regul Pept 133:68–73

Luquet S, Perez FA, Hnasko TS, Palmiter RD (2005) NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310:683–685

Chen HY, Trumbauer ME, Chen AS et al (2004) Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 145:2607–2612

Tschop M, Statnick MA, Suter TM, Heiman ML (2002) GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein. Endocrinology 143:558–568

Qian S, Chen H, Weingarth D et al (2002) Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 22:5027–5035

Gropp E, Shanabrough M, Borok E et al (2005) Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci 8:1289–1291

Ste ML, Luquet S, Cole TB, Palmiter RD (2005) Modulation of neuropeptide Y expression in adult mice does not affect feeding. Proc Natl Acad Sci USA 102:18632–18637

Bewick GA, Gardiner JV, Dhillo WS et al (2005) Post-embryonic ablation of AgRP neurons in mice leads to a lean, hypophagic phenotype. FASEB J 19:1680–1682

Diano S, Farr SA, Benoit SC et al (2006) Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 9:381–388

Carlini VP, Varas MM, Cragnolini AB, Schioth HB, Scimonelli TN, de Barioglio SR (2004) Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem Biophys Res Commun 313:635–641

Weikel JC, Wichniak A, Ising M et al (2003) Ghrelin promotes slow-wave sleep in humans. Am J Physiol Endocrinol Metab 284:E407–E415

Carlini VP, Monzon ME, Varas MM et al (2002) Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem Biophys Res Commun 299:739–743

Barlier A, Zamora AJ, Grino M et al (1999) Expression of functional growth hormone secretagogue receptors in human pituitary adenomas: polymerase chain reaction, triple in-situ hybridization and cell culture studies. J Neuroendocrinol 11:491–502

Korbonits M, Jacobs RA, Aylwin SJ et al (1998) Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. J Clin Endocrinol Metab 83:3624–3630

Adams EF, Huang B, Buchfelder M et al (1998) Presence of growth hormone secretagogue receptor messenger ribonucleic acid in human pituitary tumors and rat GH3 cells. J Clin Endocrinol Metab 83:638–642

Shimon I, Yan X, Melmed S (1998) Human fetal pituitary expresses functional growth hormone-releasing peptide receptors. J Clin Endocrinol Metab 83:174–178

Nielsen S, Mellemkjaer S, Rasmussen LM et al (1998) Gene transcription of receptors for growth hormone-releasing peptide and somatostatin in human pituitary adenomas. J Clin Endocrinol Metab 83:2997–3000

Caminos JE, Nogueiras R, Blanco M et al (2003) Cellular distribution and regulation of ghrelin messenger ribonucleic acid in the rat pituitary gland. Endocrinology 144:5089–5097

Kim K, Arai K, Sanno N, Osamura RY, Teramoto A, Shibasaki T (2001) Ghrelin and growth hormone (GH) secretagogue receptor (GHSR) mRNA expression in human pituitary adenomas. Clin Endocrinol (Oxf) 54:759–768

Garcia A, Alvarez CV, Smith RG, Dieguez C (2001) Regulation of Pit-1 expression by ghrelin and GHRP-6 through the GH secretagogue receptor. Mol Endocrinol 15:1484–1495

Soto JL, Castrillo JL, Dominguez F, Dieguez C (1995) Regulation of the pituitary-specific transcription factor GHF-1/PIT-1 messenger-ribonucleic-acid levels by growth hormone-secretagogues in rat anterior-pituitary-cells in monolayer-culture. Endocrinology 136:3863–3870

Nanzer AM, Khalaf S, Mozid AM et al (2004) Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway. Eur J Endocrinol 151:233–240

Cappiello V, Ronchi C, Morpurgo PS et al (2002) Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients. Eur J Endocrinol 147:189–194

Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML (2001) Circulating ghrelin levels are decreased in human obesity. Diabetes 50:707–709

Cummings DE, Weigle DS, Frayo RS et al (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623–1630

Freda PU, Reyes CM, Conwell IM, Sundeen RE, Wardlaw SL (2003) Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy. J Clin Endocrinol Metab 88:2037–2044

Arosio M, Ronchi CL, Gebbia C et al (2004) Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly. Eur J Endocrinol 150:27–32

Popovic V, Damjanovic S, Micic D, Petakov M, Dieguez C, Casanueva FF (1994) Growth hormone (GH) secretion in active acromegaly after the combined administration of GH-releasing hormone and GH-releasing peptide-6. J Clin Endocrinol Metab 79:456–460

Renner U, Brockmeier S, Strasburger CJ et al (1994) Growth hormone (GH)-releasing peptide stimulation of GH release from human somatotroph adenoma cells: interaction with GH-releasing hormone, thyrotropin-releasing hormone, and octreotide. J Clin Endocrinol Metab 78:1090–1096

Papotti M, Ghe C, Cassoni P et al (2000) Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 85:3803–3807

Murata M, Okimura Y, Iida K et al (2002) Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 277:5667–5674

Nagaya N, Kojima M, Uematsu M et al (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 280:R1483–R1487

Broglio F, Arvat E, Benso A et al (2001) Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 86:5083–5086

Martinez-Fuentes AJ, Moreno-Fernandez J, Vazquez-Martinez R et al (2006) Ghrelin is produced by and directly activates corticotrope cells from adrenocorticotropin-secreting adenomas. J Clin Endocrinol Metab 91:2225–2231

Otto B, Tschop M, Heldwein W, Pfeiffer AF, Diederich S (2004) Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans. Eur J Endocrinol 151:113–117

Libe R, Morpurgo PS, Cappiello V et al (2005) Ghrelin and adiponectin in patients with Cushing’s disease before and after successful transsphenoidal surgery. Clin Endocrinol (Oxf) 62:30–36

Giordano R, Picu A, Pagotto U et al (2005) The negative association between total ghrelin levels, body mass and insulin secretion is lost in hypercortisolemic patients with Cushing’s disease. Eur J Endocrinol 153:535–543

Leal-Cerro A, Torres E, Soto A et al (2002) Ghrelin is no longer able to stimulate growth hormone secretion in patients with Cushing’s syndrome but instead induces exaggerated corticotropin and cortisol responses. Neuroendocrinology 76:390–396

Andreis PG, Malendowicz LK, Trejter M et al (2003) Ghrelin and growth hormone secretagogue receptor are expressed in the rat adrenal cortex: Evidence that ghrelin stimulates the growth, but not the secretory activity of adrenal cells. FEBS Lett 536:173–179

Barreiro ML, Pinilla L, Aguilar E, Tena-Sempere M (2002) Expression and homologous regulation of GH secretagogue receptor mRNA in rat adrenal gland. Eur J Endocrinol 147:677–688

Carraro G, Albertin G, Abudukerimu A, Aragona F, Nussdorfer GG (2004) Growth hormone secretagogue receptor subtypes 1a and 1b are expressed in the human adrenal cortex. Int J Mol Med 13:295–298

Tortorella C, Macchi C, Spinazzi R, Malendowicz LK, Trejter M, Nussdorfer GG (2003) Ghrelin, an endogenous ligand for the growth hormone-secretagogue receptor, is expressed in the human adrenal cortex. Int J Mol Med 12:213–217

Mazzocchi G, Neri G, Rucinski M et al (2004) Ghrelin enhances the growth of cultured human adrenal zona glomerulosa cells by exerting MAPK-mediated proliferogenic and antiapoptotic effects. Peptides 25:1269–1277

Arvat E, Maccario M, Di Vito L et al (2001) Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab 86:1169–1174

Ciccarelli A, Guerra E, De Rosa M et al (2005) PRL secreting adenomas in male patients. Pituitary 8:39–42

Rubinfeld H, Hadani M, Taylor JE et al (2004) Novel ghrelin analogs with improved affinity for the GH secretagogue receptor stimulate GH and prolactin release from human pituitary cells. Eur J Endocrinol 151:787–795

Ciccarelli E, Grottoli S, Razzore P et al (1996) Hexarelin, a synthetic growth hormone releasing peptide, stimulates prolactin secretion in acromegalic but not in hyperprolactinaemic patients. Clin Endocrinol (Oxf) 44:67–71

Skinner MM, Nass R, Lopes B, Laws ER, Thorner MO (1998) Growth hormone secretagogue receptor expression in human pituitary tumors. J Clin Endocrinol Metab 83:4314–4320

Taal BG, Visser O (2004) Epidemiology of neuroendocrine tumours. Neuroendocrinology 80(Suppl 1):3–7

Arnold R (2005) Endocrine tumours of the gastrointestinal tract. Introduction: definition, historical aspects, classification, staging, prognosis and therapeutic options. Best Pract Res Clin Gastroenterol 19:491–505

Rindi G, Bordi C (2005) Endocrine tumours of the gastrointestinal tract: aetiology, molecular pathogenesis and genetics. Best Pract Res Clin Gastroenterol 19:519–534

Inui A, Asakawa A, Bowers CY et al (2004) Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J 18:439–456

Masuda Y, Tanaka T, Inomata N et al (2000) Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 276:905–908

Sibilia V, Pagani F, Guidobono F et al (2002) Evidence for a central inhibitory role of growth hormone secretagogues and ghrelin on gastric acid secretion in conscious rats. Neuroendocrinology 75:92–97

Peeters TL (2003) Central and peripheral mechanisms by which ghrelin regulates gut motility. J Physiol Pharmacol 54(Suppl 4):95–103

Dass NB, Munonyara M, Bassil AK et al (2003) Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin. Neuroscience 120:443–453

Salehi A, Dornonville dlC, Hakanson R, Lundquist I (2004) Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. Regul Pept 118:143–150

Arosio M, Ronchi CL, Gebbia C, Cappiello V, Beck-Peccoz P, Peracchi M (2003) Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. J Clin Endocrinol Metab 88:701–704

Gokcel A, Gumurdulu Y, Kayaselcuk F et al (2003) Helicobacter pylori has no effect on plasma ghrelin levels. Eur J Endocrinol 148:423–426

Dornonville dlC, Lindqvist A, Egecioglu E et al (2005) Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice. Gut 54:907–913

Ghigo E, Broglio F, Arvat E, Maccario M, Papotti M, Muccioli G (2005) Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol (Oxf) 62:1–17

Papotti M, Cassoni P, Volante M, Deghenghi R, Muccioli G, Ghigo E (2001) Ghrelin-producing endocrine tumors of the stomach and intestine. J Clin Endocrinol Metab 86:5052–5059

Rindi G, Savio A, Torsello A et al (2002) Ghrelin expression in gut endocrine growths. Histochem Cell Biol 117:521–525

Volante M, Allia E, Gugliotta P et al (2002) Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 87:1300–1308

Corbetta S, Peracchi M, Cappiello V et al (2003) Circulating ghrelin levels in patients with pancreatic and gastrointestinal neuroendocrine tumors: identification of one pancreatic ghrelinoma. J Clin Endocrinol Metab 88:3117–3120

Tsolakis AV, Portela-Gomes GM, Stridsberg M et al (2004) Malignant gastric ghrelinoma with hyperghrelinemia. J Clin Endocrinol Metab 89:3739–3744

Toshinai K, Mondal MS, Nakazato M et al (2001) Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 281:1220–1225

Shiiya T, Nakazato M, Mizuta M et al (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87:240–244

Raffel A, Krausch M, Cupisti K, Gerharz CD, Eisenberger CF, Knoefel WT (2005) Ghrelin expression in neuroendocrine tumours of the gastrointestinal tract with multiple endocrine neoplasia type 1. Horm Metab Res 37:653–655

Ekeblad S, Nilsson B, Lejonklou MH et al (2006) Gastrointestinal stromal tumors express the orexigen ghrelin. Endocr Relat Cancer 13:963–970.

Jeffery PL, Herington AC, Chopin LK (2003) The potential autocrine/paracrine roles of ghrelin and its receptor in hormone-dependent cancer. Cytokine Growth Factor Rev 14:113–122

Duxbury MS, Waseem T, Ito H et al (2003) Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 309:464–468

Zhang YF, Wang HN, Hong TP (2006) Ghrelin expression in the tissues of different thyroid diseases. Beijing Da Xue Xue Bao 38:193–196

Gaytan F, Barreiro ML, Chopin LK et al (2003) Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary. J Clin Endocrinol Metab 88:879–887

Gaytan F, Morales C, Barreiro ML et al (2005) Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors. J Clin Endocrinol Metab 90:1798–1804

Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22:255–288

Gaytan F, Barreiro ML, Caminos JE et al (2004) Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J Clin Endocrinol Metab 89:400–409

Tena-Sempere M, Barreiro ML, Gonzalez LC et al (2002) Novel expression and functional role of ghrelin in rat testis. Endocrinology 143:717–725

Barreiro ML, Gaytan F, Castellano JM et al (2004) Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis. Endocrinology 145:4825–4834

Kierson JA, Dimatteo DM, Locke RG, Mackley AB, Spear ML (2006) Ghrelin and cholecystokinin in term and preterm human breast milk. Acta Paediatr 95:991–995

Savino F, Lupica MM (2006) Breast milk: biological constituents for health and well-being in infancy. Recenti Prog Med 97:519–527