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2011 | 55 | 3 |
Tytuł artykułu

Influence of intragastric administration of ghrelin receptor antagonist [D-Lys3]-ghrp-6 on bone tissue in rats

Warianty tytułu
Języki publikacji
The aim of the study was to investigate the influence of [D-Lys3]-growth hormone releasing peptide-6 (GHRP-6), an antagonist of GHS-R1a, on the growth performance and properties of bone tissue in rats. The studies were performed on 12 male Wistar rats, divided into two equal groups. Control rats received 0.5 ml of physiological saline, while experimental rats received intragastrically 100 nmol/kg b.w. of [D-Lys3]-GHRP-6 once a day, throughout 4 weeks. After that time, the animals were subjected to euthanasia. tBMC, tBMD, lean mass (LM), and fat mass (FM) contents were measured using DEXA methods. Plasma level of total ghrelin was also measured. The quality of the femur and tibia was estimated based on their weight, length, BMC, and BMD. [D- Lys3]-GHRP-6 decreased final body weight, LM content, and tBMD, and significantly reduced bone weight and BMC as compared to the control group. No significant differences were noted in bone length and BMD. Plasma level of total ghrelin was significantly higher after the treatment. We concluded that the intragastric treatment with [D-Lys3]-GHRP-6 negatively influenced the growth performance and properties of bone in rats. Therefore, ghrelin probably achieves effect in bone by acting on its specific receptor GHS-R1a.
Opis fizyczny
  • Department of Animal Biochemistry and Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
  • 1. Asakawa A., Inui A., Kaga T., Katsuura G., Fujimiya A., Fujino M.A., Kasuga M.: Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003, 52, 947-952.
  • 2. Camina J.P.: Cell biology of the ghrelin receptor. J Neuroendocrinol 2006, 18, 65-76.
  • 3. Choi K., Roh S.G., Hong Y.H., Shrestha Y.B., Hishikawa D., Chen C., Kojima M., Kangawa K., Sasaki S.: The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. Endocrinology 2003, 144, 754-759.
  • 4. Cocchi D., Maccarinelli G., Sibila V., Tulipano G., Torsello A., Pazzaglia V.E., Giustina A., Netti C.: GH- releasing peptides and bone. J Endocrinol Invest 2005, 28 (8 suppl.), 11-14.
  • 5. Delhanty P.J., Eerden B.C., Velde M., Gauna C., Pols H.A., Jahr H., Chiba H., van der Lely A.J., van Leeuwen J.P.T.M.: Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) pathways in the absence of GHSR- 1a. J Endocrinol 2006, 188, 37-47.
  • 6. Deng F.L., Ling J.Q., Ma J.Y., Liu C.H., Zhang W.: Stimulation of intramembranous bone repair by ghrelin. Exp Physiol 2008, 937, 872-879.
  • 7. Fukushima N., Hanada R., Teranishi H., Fukue Y., Tachibana T., Ishikawa H., Takeda S., Takeuchi Y., Fukumoto S., Kangawa K., Nagata K., Kojima M.: Ghrelin directly regulates bone formation. J Bone Miner Res 2005, 20, 790-798.
  • 8. Gaytan F., Barreiro M.L., Caminos J.E., Chopin L.K., Herimgton A.C., Morales C., Pinilla L., Paniagua R., Nistal M., Casanueva F.F., Aguilar E., Diegez C., Tena- Sempere M.: Expression of ghrelin and its functional receptor, the type la growth hormone secretagogue receptor, in normal human testis and testicular tumors. J Clin Endocrinol Metab 2004, 89, 400-409.
  • 9. Gaytan F., Brreiro M.L., Chopin L.K., Herington A.C., Morales C., Pinilla L., Casanueva F.F., Aguilar E., Dieguez C., Tena-Sempere M.: Immunolocalization of ghrelin and its functional receptor, the type la growth hormone secretagogue receptor, in the cyclic human ovary. J Clin Endocrinol Metab 2003, 88, 879-887.
  • 10. Gnanapavan S., Kola B., Bustin S.A., Morris D.G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A.B., Korbonits M.: 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.
  • 11. Gualillo O., Caminos J.E., Kojima M., Kangawa K., Arvat E., Ghigo E., Casanueva F.F., Dieguez C.: Gender and gonadal influences on ghrelin mRNA levels in rat stomach. Eur J Endocrinol 2001, 44, 687-690.
  • 12. Hansen T.K., Dall R., Hosoda H., Kojima M., Kangawa K., Christiansen J.S., Jorgensen J.O.L.: Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol 2002, 56, 203-206.
  • 13. Howard A.D., Feighner S.D., Cully D.F., Arena J.P., Liberator P.A., Rosenblum C.I., Hamelin M., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C., Chou M., Liu K.K., McKee K.K., Pong S.S., Chaung L.Y., Elbrecht A., Dashkevicz M., Haevens R., Rigby M., Sirinathsinghji D.J.S., Dean D.C., Melillo D.G., Patchett A.A., Nargund R., Griffin P.R., DeMartino J.A., Gupta S.K., Schaeffer J.M., Smith R.G., Van der Ploeg L.T.H.: A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996, 273, 974-976.
  • 14. Kim S.W., Her S.J., Park S.J., Kim D., Park K.S., Lee H.K., Han B.H., Kim M.S., Shin Ch.S., Kim S.Y.: Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells. Bone 2005, 37, 359-369.
  • 15. 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.
  • 16. Kojima M., Hosoda H., Matsuo H., Kangawa K.: Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab 2001, 12, 118-122.
  • 17. Kojima M., Kangawa, K.: Drug insight: the functions of ghrelin and its potential as a multitherapeutic hormone. Nat Clin Pract Endocrinol Metab 2006, 2, 80-88.
  • 18. Kos K., Harte A. L., O'Hare P. J., Kumar S., McTernan P. G.: Ghrelin and the differential regulation of des-acyl (DSG) and oct-anoyl ghrelin (OTG) in human adipose tissue (AT). Clin Endocrinol 2009, 70, 383-389.
  • 19. Maccarinelli G., Sibilia V., Torsello A., Raimondo F., Pitto M., Giustina A., Netti C., Cocchi D.: Ghrelin regulates proliferation and differentiation of osteoblastic cells. J Endocrinol 2005, 184, 249-256.
  • 20. McKee K.K., Tan C.P., Palyha O.C., Liu J., Feighner S.D., Hreniuk D.L., Smith R.G., Howard A.D., Van der Ploeg L.H.: Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. Genomics 1997, 52, 223-229.
  • 21. McKee K.K., Palyha O.C., Feighner S.D., Hreniuk D.L., Tan C.P., Phillips M.S., Smith R.G., Van der Ploeg L.H., Howard A.D.: Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol Endocrinol 1997, 11, 415-423.
  • 22. Miao Y., Xia Q., Hou Z.S., Zheng Y., Pan H., Zhu S.G.: Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats. Biochem Biophys Res Commun 2007, 359, 795-800.
  • 23. Misra M., Miller K., Stewart V., Hunter E., Kuo K., Herzog D., Klibanski A.: Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metab 2005, 90, 5082-5087.
  • 24. Muccioli G., Pons N., Ghe C., Capatano F., Granata R., Ghigo E., Nogueiras R., Perez-Tilve D., Pfluger P., Castaneda T.R., Muzzin P., Schürmann A., Szanto I., Tschöp M.H., Rohner-Jeanrenaud F.: Ghrelin and des- acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor. Europ J Pharmacol 2004, 498, 27- 35.
  • 25. Nakazato M., Murakami N., Date Y., Kojima M., Matsuo H., Kangawa K., Matsukura S.: A role for ghrelin in the central regulation of feeding. Nature 2001, 409, 194-198.
  • 26. Olney R.C.: Regulation of bone mass by growth hormone. Med Pediatr Oncol 2003, 41, 228-234.
  • 27. Sun Y., Ahmed S., Smith R.G.: Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003, 23, 7973-7981.
  • 28. Shuto Y., Shibasaki T., Wada K., Parhar I., Kamegai J., Sugihara H., Oikawa S., Wakabayashu I.: Generation of polyclonal antiserum against the growth hormone secretagogue receptor (GHS-R): Evidence that the GHS- R exists in the hypothalamus, pituitary and stomach of rats. Life Sei 2001, 68, 991-996.
  • 29. Theander-Carrillo C., Wiedmer P., Cettour-Rose P., Nogueiras R., Perez-Tilve D., Pfluger P., Castaneda T.R., Muzzin P.: Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 2006, 116, 1983-1993.
  • 30. Thompson N.M., Gill D.A., Davies R., Loveridge N., Houston P.A., Robinson I.C.A.F., Wells T.: 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.
  • 31. Warzecha Z., Dembiński A., Ceranowicz P., Dembiński M., Cieszkowski J., Konturek S.J., Polus A., Pawlik W.W., Kuwahara A., Kato I., Konturek P.C.: Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats. J Physiol Pharm 2006, 57, 425-437.
  • 32. Wierup N., Yang S., McEvilly R.J., Mulder H., Sundler F.: Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J Histochem Cytochem 2004, 52, 301-310.
  • 33. Wren A.M., Seal L.J., Cohen M.A., Brynes A. E., Frost G.S., Murphy K. G., Dhillo W. S., Ghatei M. A., Bloom S. R.: Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001, 86, 5992-5995.
  • 34. Xu G., Li Y., An W., Zhang W.: Ghrelin and cell differentiation. Acta Biochim Biophys Sin 2008, 40, 841- 847.
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