Ghrelin gene-related peptides: Multifunctional endocrine/autocrine modulators in health and disease

Clinical and Experimental Pharmacology and Physiology

Volumn 37, Issue 1, 2010, Pages 125-131

  Seim, Inge ^a   Amorim, Laura ^a   Walpole, Carina ^a   Carter, Shea ^a   Chopin, Lisa K ^a   Herington, Adrian C ^a  

^a QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

Author keywords

Gene expression; Ghrelin; Hormone dependent cancers; Obestatin

Indexed keywords

GHRELIN; GHRELIN RECEPTOR; MESSENGER RNA; OBESTATIN; PROTEIN PRECURSOR;

AUTOCRINE EFFECT; CELL PROLIFERATION; CONFERENCE PAPER; DIABETES MELLITUS; ENDOCRINE FUNCTION; GENE LOCUS; NEOPLASM; OBESITY; PROTEIN DEGRADATION; RNA SPLICING; RNA TRANSCRIPTION;

ALTERNATIVE SPLICING; ANIMALS; APPETITE REGULATION; EATING; GENE EXPRESSION REGULATION; GHRELIN; HUMANS; NEOPLASMS; OBESITY; PEPTIDE HORMONES; RECEPTORS, GHRELIN;

EID: 74049092773     PISSN: 03051870     EISSN: 14401681     Source Type: Journal    
DOI: 10.1111/j.1440-1681.2009.05241.x     Document Type: Conference Paper

References (81)

1. 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.
2. Howard AD, Feighner SD, Cully DF et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996 273 : 974 977.
3. 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 4261.
4. Higgins SC, Gueorguiev M, Korbonits M. Ghrelin, the peripheral hunger hormone. Ann. Med. 2007 39 : 116 136.
5. Leite-Moreira AF, Soares JB. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov. Today 2007 12 : 276 288.
6. Wajnrajch MI, Gertner J, Leibel R. Genomic organization of the GHRELIN gene. J. Endocr. Genet. 2000 1 : 231 233.
7. Takada R, Satomi Y, Kurata T et al. Monounsaturated fatty acid modification of Wnt protein: Its role in Wnt secretion. Dev. Cell 2006 11 : 791 801.
8. Gutierrez JA, Solenberg PJ, Perkins DR et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc. Natl Acad. Sci. USA 2008 105 : 6320 6325.
9. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008 132 : 387 396.
10. Patterson M, Murphy KG, le Roux CW, Ghatei MA, Bloom SR. Characterization of ghrelin-like immunoreactivity in human plasma. J. Clin. Endocrinol. Metab. 2005 90 : 2205 2211.
11. 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.
12. Bedendi I, Alloatti G, Marcantoni A et al. Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin. Eur. J. Pharmacol. 2003 476 : 87 95.
13. Broglio F, Gottero C, Prodam F et al. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J. Clin. Endocrinol. Metab. 2004 89 : 3062 3065.
14. Cassoni P, Ghe C, Marrocco T et al. Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines. Eur. J. Endocrinol. 2004 150 : 173 184.
15. Thompson NM, Gill DA, Davies R et al. Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the Type 1a growth hormone secretagogue receptor. Endocrinology 2004 145 : 234 242.
16. Gauna C, Delhanty PJ, Hofland LJ et al. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J. Clin. Endocrinol. Metab. 2005 90 : 1055 1060.
17. Toshinai K, Yamaguchi H, Sun Y et al. Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 2006 147 : 2306 2314.
18. Muccioli G, Pons N, Ghe C, Catapano F, Granata R, Ghigo E. Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-Type 1a growth hormone secretagogue receptor. Eur. J. Pharmacol. 2004 498 : 27 35.
19. Asakawa A, Inui A, Fujimiya M et al. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut 2005 54 : 18 24.
20. Holst B, Holliday ND, Bach A, Elling CE, Cox HM, Schwartz TW. Common structural basis for constitutive activity of the ghrelin receptor family. J. Biol. Chem. 2004 279 : 53806 53817. (Pubitemid 40051890)
21. Petersenn S, Rasch AC, Penshorn M, Beil FU, Schulte HM. Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor. Endocrinology 2001 142 : 2649 2659.
22. 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 2991.
23. Jeffery PL, Herington AC, Chopin LK. Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines. J. Endocrinol. 2002 172 : R7 11.
24. Barzon L, Pacenti M, Masi G, Stefani AL, Fincati K, Palu G. Loss of growth hormone secretagogue receptor 1a and overexpression of Type 1b receptor transcripts in human adrenocortical tumors. Oncology 2005 68 : 414 421.
25. Jeffery PL, Murray RE, Yeh AH et al. Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr. Relat. Cancer 2005 12 : 839 850.
26. Takahashi K, Furukawa C, Takano A et al. The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Cancer Res. 2006 66 : 9408 9419.
27. McKee KK, Palyha OC, Feighner SD et al. Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol. Endocrinol. 1997 11 : 415 423.
28. Yeh AH, Jeffery PL, Duncan RP, Herington AC, Chopin LK. Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin. Cancer Res. 2005 11 : 8295 8303.
29. Rossi F, Castelli A, Bianco MJ, Bertone C, Brama M, Santiemma V. Ghrelin induces proliferation in human aortic endothelial cells via ERK1/2 and PI3K/Akt activation. Peptides 2008 29 : 2046 2051.
30. Nanzer AM, Khalaf S, Mozid AM et al. Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway. Eur. J. Endocrinol. 2004 151 : 233 240.
31. Malagon MM, Luque RM, Ruiz-Guerrero E et al. Intracellular signaling mechanisms mediating ghrelin-stimulated growth hormone release in somatotropes. Endocrinology 2003 144 : 5372 5380.
32. Mousseaux D, Le Gallic L, Ryan J et al. Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCvarepsilon pathway. Br. J. Pharmacol. 2006 148 : 350 365.
33. Granata R, Settanni F, Biancone L et al. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: Involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signalling. Endocrinology 2007 148 : 512 529.
34. i via AMPK in hypothalamic arcuate nucleus NPY neurons. Biochem. Biophys. Res. Commun. 2008 366 : 388 392.
35. Jiang H, Betancourt L, Smith RG. Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol. Endocrinol. 2006 20 : 1772 1785.
36. Smith RG. Is ghrelin playing a role in the regulation of insulin release? In : Proceedings of the 90th Annual Meeting of the Endocrine Society, 15-18 June 2008, San Francisco. The Endocrine Society, Baltimore. 2008 S75 2 (Abstract).
37. Chan CB, Cheng CH. Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli. Mol. Cell. Endocrinol. 2004 214 : 81 95.
38. Leung PK, Chow KB, Lau PN et al. The truncated ghrelin receptor polypeptide (GHS-R1b) acts as a dominant-negative mutant of the ghrelin receptor. Cell. Signal. 2007 19 : 1011 1022.
39. Seim I, Collet C, Herington AC, Chopin LK. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics 2007 8 : 298 314.
40. Kanamoto N, Akamizu T, Tagami T et al. Genomic structure and characterization of the 5′-flanking region of the human ghrelin gene. Endocrinology 2004 145 : 4144 4153.
41. Nakai N, Kaneko M, Nakao N et al. Identification of promoter region of ghrelin gene in human medullary thyroid carcinoma cell line. Life Sci. 2004 75 : 2193 2201.
42. Kojima M, Kangawa K. Ghrelin: Structure and function. Physiol. Rev. 2005 85 : 495 522.
43. Pemberton C, Wimalasena P, Yandle T, Soule S, Richards M. C-Terminal pro-ghrelin peptides are present in the human circulation. Biochem. Biophys. Res. Commun. 2003 310 : 567 573.
44. Zhang JV, Ren PG, Avsian-Kretchmer O et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 2005 310 : 996 999.
45. Hosoda H, Kojima M, Mizushima T, Shimizu S, Kangawa K. Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. J. Biol. Chem. 2003 278 : 64 70.
46. Hosoda H, Kojima M, Matsuo H, Kangawa K. Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J. Biol. Chem. 2000 275 : 21995 21000.
47. Tanaka M, Hayashida Y, Iguchi T, Nakao N, Nakai N, Nakashima K. Organization of the mouse ghrelin gene and promoter: Occurrence of a short noncoding first exon. Endocrinology 2001 142 : 3697 3700.
48. Jeffery PL, Duncan RP, Yeh AH et al. Expression of the ghrelin axis in the mouse: An exon 4-deleted mouse proghrelin variant encodes a novel C terminal peptide. Endocrinology 2005 146 : 432 440.
49. Tanaka M, Hayashida Y, Nakao N, Nakai N, Nakashima K. Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse. Biochim. Biophys. Acta 2001 1522 : 62 5.
50. Kineman RD, Gahete MD, Luque RM. Identification of a mouse ghrelin gene transcript that contains intron 2 and is regulated in the pituitary and hypothalamus in response to metabolic stress. J. Mol. Endocrinol. 2007 38 : 511 521.
51. Yang J, Zhao TJ, Goldstein JL, Brown MS. Inhibition of ghrelin O-acyltransferase (GOAT) by octanoylated pentapeptides. Proc. Natl Acad. Sci. USA 2008 105 : 10750 10755.
52. Bednarek MA, Feighner SD, Pong SS et al. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: Minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J. Med. Chem. 2000 43 : 4370 4376.
53. Tang S-Q, Jiang Q-Y, Zhang Y-LZ et al. Obestatin: Its physicochemical characteristics and physiological functions. Peptides 2008 29 : 629 645.
54. Chen CY, Fujimiya M, Asakawa A et al. At the cutting edge: Ghrelin general products in food intake and gut motility. Neuroendocrinology 2009 89 : 9 17.
55. Lauwers E, Landuyt B, Arckens L, Schoofs L, Luyten W. Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem. Biophys. Res. Commun. 2006 351 : 21 5.
56. Holst B, Egerod KL, Schild E et al. GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 2007 148 : 13 20.
57. 2+as an endogenous agonist of GPR39 from fetal bovine serum. J. Recept. Signal Transduct. Res. 2007 27 : 235 246.
58. Alvarez C, Lodeiro M, Theodoropoulou M, Camina J, Casanueva F, Pazos Y. Obestatin stimulates Akt signalling in gastric cancer cells through β-arrestin-mediated epidermal growth factor receptor transactivation. Endocr. Relat. Cancer 2009 16 : 599 611.
59. Pan W, Tu H, Kastin AJ. Differential BBB interactions of three ingestive peptides. Obestatin, ghrelin, and adiponectin. Peptides 2006 27 : 911 916.
60. Pazos Y, Alvarez CJ, Camina JP, Casanueva FF. Stimulation of extracellular signal-regulated kinases and proliferation in the human gastric cancer cells KATO-III by obestatin. Growth Factors 2007 25 : 373 381.
61. Camina JP, Campos JF, Caminos JE, Dieguez C, Casanueva FF. Obestatin-mediated proliferation of human retinal pigment epithelial cells: Regulatory mechanisms. J. Cell. Physiol. 2007 211 : 1 9.
62. Meszarosova M, Sirotkin AV, Grossmann R, Darlak K, Valenzuela F. The effect of obestatin on porcine ovarian granulosa cells. Anim. Reprod. Sci. 2008 108 : 196 207.
63. Szentirmai E, Krueger JM. Obestatin alters sleep in rats. Neurosci. Lett. 2006 404 : 222 226.
64. Carlini VP, Schioth HB, Debarioglio SR. Obestatin improves memory performance and causes anxiolytic effects in rats. Biochem. Biophys. Res. Commun. 2007 352 : 907 912.
65. Samson WK, White MM, Price C, Ferguson AV. Obestatin acts in brain to inhibit thirst. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007 292 : R637 43.
66. Bang AS, Soule SG, Yandle TG, Richards AM, Pemberton CJ. Characterisation of proghrelin peptides in mammalian tissues and plasma. J. Endocrinol. 2007 192 : 313 323.
67. Jeffery PL, Herington AC, Chopin LK. The potential autocrine/paracrine roles of ghrelin and its receptor in hormone-dependent cancer. Cytokine Growth Factor Rev. 2003 14 : 113 122.
68. Seim I, Carter SL, Herington AC, Chopin LK. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene. BMC Mol. Biol. 2008 9 : 95 117.
69. McCracken S, Fong N, Rosonina E et al. 5′-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II. Genes Dev. 1997 11 : 3306 3318.
70. Ravasi T, Suzuki H, Pang KC et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Res. 2006 16 : 11 9.
71. Sasaki YT, Sano M, Ideue T, Kin T, Asai K, Hirose T. Identification and characterization of human non-coding RNAs with tissue-specific expression. Biochem. Biophys. Res. Commun. 2007 357 : 991 996.
72. Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS. Specific expression of long noncoding RNAs in the mouse brain. Proc. Natl Acad. Sci. USA 2008 105 : 716 721.
73. Torarinsson E, Yao Z, Wiklund ED et al. Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Res. 2008 18 : 242 251.
74. Sleutels F, Zwart R, Barlow DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 2002 415 : 810 813.
75. Tam OH, Aravin AA, Stein P et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 2008 453 : 534 538.
76. Watanabe T, Totoki Y, Toyoda A et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 2008 453 : 539 543.
77. Carlile M, Nalbant P, Preston-Fayers K, McHaffie GS, Werner A. Processing of naturally occurring sense/antisense transcripts of the vertebrate Slc34a gene into short RNAs. Physiol. Genomics 2008 34 : 95 100.
78. Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science 2008 320 : 1336 1341.
79. Eis PS, Tam W, Sun L et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc. Natl Acad. Sci. USA 2005 102 : 3627 3632.
80. Kim VN, Nam JW. Genomics of microRNA. Trends Genet. 2006 22 : 165 173.
81. Rodriguez A, Vigorito E, Clare S et al. Requirement of bic/microRNA-155 for normal immune function. Science 2007 316 : 608 611.