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Effect of Twice Daily Administration of GH-releasing Peptide-2 for 10 Days on Growth Performance, Plasma GH Responses and Insulin-like Growth Factor-1 Concentrations in Swine

  • Nou, V. (Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine) ;
  • Inoue, H. (Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine) ;
  • Lee, H.G. (Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine) ;
  • Matsunaga, N. (Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine) ;
  • Kuwayama, H. (Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine) ;
  • Hidari, H. (Laboratory of Animal Production, Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine)
  • Received : 2002.09.26
  • Accepted : 2003.02.28
  • Published : 2003.08.01

Abstract

An increase in frequency of administration of exogenous growth hormone (GH) or GH-releasing hormone was reported to be a model to increase blood circulating insulin-like growth factor-1 (IGF-1) and to improve growth performance in animals. We have investigated the effect of twice daily administration of GH-releasing peptide-2 (GHRP-2) on growth performance, GH responsiveness and plasma insulin-like growth factor IGF-1 in swine. We administered to eight swine, 3 control and 5 treatment, a twice daily s.c. injections of GHRP-2 ($30{\mu}g/kg\;BW$) for a period of 10 days. Every day blood samples immediately taken before injections of GHRP-2 or saline, at 08:00 h and 16:00 h, were measured for IGF-1 concentrations. Blood samples for GH assay were collected every 20 min on days 1, 6 and 10, from 1 hour before and 3 h after GHRP-2 or saline injections at 08:00 h. GH peak concentrations and GH area under curve (GH AUC) on day 1, 6 and 10 in treatment group of swine were higher than those in control swine (p<0.05). Twice daily administration of GHRP-2 caused a significantly attenuation (p<0.05) of GH peak concentrations ($80.25{\pm}13.87$, $39.73{\pm}5.72$ and $27.57{\pm}6.06ng/ml$ for day 1, 6 and 10, respectively) and GH AUCs ($3,536.15{\pm}738.35$, $1,310.31{\pm}203.55$ and $934.37{\pm}208.99ng/ml$ for day 1, 6 and 10, respectively). However, there was no significant difference in GH peak concentration and GH AUC between day 6 and 10. Plasma IGF-1 concentration levels were higher in treatment than control group of swine (p<0.05) after 3 days of the treatment, and the levels reached a plateau from day 3 to 10 of experiment. Growth performance did not alter by GHRP-2 administration, even though a numerical increase of body weight gain and feed efficiency was observed. These results indicate that twice daily administration of GHRP-2 for 10 days in swine did not significantly influence on growth performance, caused an overall attenuation of GH response, and that elevation of plasma GH concentrations caused by GHRP-2 administration increased plasma IGF-1 concentrations, even though an attenuation of GH response was observed.

Keywords

References

  1. Bick, T., Z. Hochberg, T. Amit, O. G. Isaksson and J. O. Jansson. 1992. Roles of pulsatility and continuity of growth hormone (GH) administration in the regulation of hepatic GH-receptors, and circulating GH-binding protein and insulin-like growth factor-I. Endocrinology 131:423-429. https://doi.org/10.1210/en.131.1.423
  2. Bowers, C. Y. and R. Granda-Ayala. 2001. Growth hormone/insulin-like growth factor-1 response to acute and chronic growth hormone-releasing peptide-2, growth hormonereleasing hormone 1-44NH2 and in combination in older men and women with decreased growth hormone secretion. Endocrine 14:79-86. https://doi.org/10.1385/ENDO:14:1:079
  3. Brameld, J. M., J. L. Atkinson, J. C. Saunders, J. M. Pell, P. J. Buttery and R. S. Gimour. 1996. Effects of growth hormone administration and dietary protein intake on insulin-like growth factor-I and growth hormone receptor mRNA expression in porcine liver, skeletal muscle and adipose tissue. J. Anim. Sci. 74:1832-1841. https://doi.org/10.2527/1996.7481832x
  4. Coleman, M. E., L. Russell and T. D. Etherton. 1994. Porcine somatotropin (pST) increases IGF-1 mRNA abundance in liver and subcutaneous (s.c.) adipose tissue but not in skeletal muscle of growing pigs. J. Anim. Sci. 72:918-924. https://doi.org/10.2527/1994.724918x
  5. Daughaday, W. H., K. Hall and M. S. Raben. 1972. Somatomedin: a proposed designation for the 'sulphation factor'. Nature 235:107-109. https://doi.org/10.1038/235107a0
  6. Daughaday, W. H., I. K. Mariz and S. L. Blethen. 1980. Inhibition of assess of bound somatomedin to membrane receptor and immunobinding sites: A comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanolextracted serum. J. Clin. Endocrinol. Metab. 51:781-788. https://doi.org/10.1210/jcem-51-4-781
  7. Dubreuil, P., D. Peticlerc, P. Gaudreau, P. Brazeau and G. Pelletier. 1991. Effect of growth hormone-releasing factor infusion on somatotropin, prolactin, thyroxine, insulin, insulin-like growth factor-I and blood metabolites in control and somatostatinimmunized growing pigs. Domest. Anim. Endocrinol 8:307-321. https://doi.org/10.1016/0739-7240(91)90066-S
  8. Dubreuil, P., D. Petitclerc, G. Pelletier, P. Gaudreau, C. Farmer, T. F. Mowles and P. Brazeau. 1990. Effect of dose and frequency of administration of a potent analog of human growth hormone-releasing factor on hormone secretion and growth in pigs. J. Anim. Sci. 68:1254-1268. https://doi.org/10.2527/1990.6851254x
  9. Etherton, T. D., J. P. Wiggins, C. M. Evock, C. S. Chung, J. F. Rebhun, P. E. Walton and N. C. Steele. 1987. Stimulation of pig growth performance by porcine growth hormone: determination of the dose-response relationship. J. Anim. Sci. 64:433-443. https://doi.org/10.2527/jas1987.642433x
  10. Ghigo, E., L. Gianotti, E. Arvat, J. Ramunni, M. R. Valetto, F. Broglio, M. Rolla, F. Cavagnini and E. E. Muller. 1999. Effects of rhIGF-1 administration on GH secretion both spontaneous and stimulated by GHRH or hexarelin, a peptidyl GH secretagogue in humans. J. Clin. Endocrinol. Metab. 84:285-290. https://doi.org/10.1210/jc.84.1.285
  11. Gondo, R. G., M. H. Aguiar-Oliveira, C. Y. Hayashida, S. P. Toledo, N. Abelin, M. A. Levine, C. Y. Bowers, A. H. Souza, R. M. Pereira, N. L. Santos and R. Salvatori. 2001. Growth hormone-releasing peptide-2 stimulates GH secretion in GHdeficient patients with mutated GH-releasing hormone receptor. J. Clin. Endocrinol. Metab. 86:3279-3283. https://doi.org/10.1210/jc.86.7.3279
  12. Hashimizume, T., K. Sasaki, S. Kobayashi and Y. Nitta. 1998. Intrahypothalamic perfusion of GHRP-2 stimulates growth hormone release in goats. Endocrine J. 45:53-59. https://doi.org/10.1507/endocrj.45.53
  13. Jansson, J. O., K. Albertsson-Wikland, S. Eden, K. G. Thorngren and O. Isaksson. 1982. Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats. Acta Physiol. Scand. 114: 261-265. https://doi.org/10.1111/j.1748-1716.1982.tb06980.x
  14. Jorgensen, J. O., W. F. Blum, N. Moller, M. B. Ranke and J. S. Christiansen. 1991. Short-term changes in serum insulin-like growth factors (IGF) and IGF binding protein 3 after different modes of intravenous growth hormone (GH) exposure in GHdeficient patients. J. Clin. Endocrinol. Metab. 72: 582-587. https://doi.org/10.1210/jcem-72-3-582
  15. Jorgensen, J. O., N. Moller, T. Lauritzen and J. S. Christiansen. 1990. Pulsatile versus continuous intravenous administration of growth hormone (GH) in GH-deficient patients: effects on circulating insulin-like growth factor-I and metabolic indices. J. Clin. Endocrinol. Metab. 70:1616-1623. https://doi.org/10.1210/jcem-70-6-1616
  16. Kensinger, R. S., L. M. McMunn, R. K. Stover, B. R. Schricker, M. L. Maccecchini, H. W. Harpster and J. F. Kavanaugh. 1987. Plasma somatotropin response to exogenous growth hormone releasing factor in lambs. J. Anim. Sci. 64:1002-1009. https://doi.org/10.2527/jas1987.6441002x
  17. Korytko, A. I. and L. Cuttler. 2001. Regulation of GHRH receptor gene expression in the neonatal and adult rat pituitary. GH & IGF Res. 11:282-288. https://doi.org/10.1054/ghir.2001.0238
  18. Kovacs, M., R. D. Kineman, A. V. Schally, B. Flerko and L. A. Frohman. 2000. Increase in mRNA concentrations of pituitary receptors for growth hormone-releasing factor and growth hormone secretagogues after neonatal monosodium glutamate treatment. J. Neuroendocrinol. 12:335-341. https://doi.org/10.1046/j.1365-2826.2000.00458.x
  19. Lee, H. G., R. A. Vega, L. T. Phung, N. Matsunaga, H. Kuwayama and H. Hidari. 2000. The effect of growth-releasing peptide-2 (GHRP-2) administration on plasma insulin-like growth factor (IGF)-1 and IGF-binding proteins in Holstein steers on different planes of nutrition. Domest. Anim. Endocrinol. 18:293-308. https://doi.org/10.1016/S0739-7240(00)00051-5
  20. Ling, S. C, F. Esch, P. Bohlen, P. Brazeau, W. B. Wehrenberg and M. G. Rosenfeld. 1993. Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 364:208-213. https://doi.org/10.1038/364208a0
  21. Min, S. H., D. D. S. Mackenzie, B. H. Breier, S. N. Mccutcheon and P. D. Gluckman. 1996. Responses of young energyrestricted sheep to chronically administered insulin-like growth factor-I (IGF-1): evidence that IGF-1 suppresses the hepatic growth hormone receptor. Endocrinology 137:1129-1137. https://doi.org/10.1210/en.137.3.1129
  22. Nakagawa, T., K. Ukai, T. Ohyama, M. Koida and H. Okamura. 1996. Effects of the synthesized growth hormone releasing peptide, KP-102, on growth hormone release in sodium glutamate monohydrate-treated low growth rats. Life Sci. 59:705-712. https://doi.org/10.1016/0024-3205(96)00356-6
  23. Nijland, E. A., C. J. Strasburger, C. P. Snijders, P. S. Van der wal and E. A. Van der veen. 1998. A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulinlike growth factor-I secretion in healthy young men. Eur. J. Endocrinol. 139:395-401. https://doi.org/10.1530/eje.0.1390395
  24. Phung, L. T., H. Inoue, V. Nou, H. G. Lee, R. A. Vega, N. Matsunaga, S. Hidaka, H. Kuwayama and H. Hidari. 2000. The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine. Domest. Anim. Endocrinol. 18:279-291.
  25. Phung, L. T., N. Matsunaga, S. Hidaka, H. Kuwayama and H. Hidari. 2001. Growth hormone-releasing peptide-2 (GHRP-2) acts synergistically with growth hormone-releasing hormone (GHRH) to release growth hormone (GH) in swine. Anim. Sci. J. (Jpn), 72:315-321.
  26. Raun, K., B. S. Hansen, N. L. Johansen, H. Thogersen, K. Madsen, M. Andersen and P. H. Andersen.1998. Ipamorelin, the first selective growth hormone secretagogue. Eur. J. Endocrinol. 139:552-561. https://doi.org/10.1530/eje.0.1390552
  27. Roh, S. G., N. Matsunaga, S. Hidaka and H. Hidari. 1996. Characteristics of growth hormone secretion responsiveness to growth hormone-releasing peptide-2 (GHRP-2 or KP102) in calves. Endocrine J. 43:291-298. https://doi.org/10.1507/endocrj.43.291
  28. Roh, S. G., M. L. He, N. Matsunaga, S. Hidaka and H. Hidari. 1997. Mechanisms of action of growth hormone-releasing peptide-2 in bovine pituitary cells. J. Anim. Sci. 75:2744-2748.
  29. Sawada, H., H. Sugihara, H. Onose, S. Minami, T. Shibasaki and I. Wakabayashi. 1994. Effect of D-Ala-D-$\beta$Nal-Ala-Trp-D-Phe-Lys-$NH_2$ (GHRP-2) on GH secretion urethan-unesthetised rats. Regul. Pepts. 53:195-210. https://doi.org/10.1016/0167-0115(94)90168-6
  30. Shah, N., W. S. Evans, C. Y. Bowers and J. D. Veldhuis. 1999. Tripartite neuroendocrine activation of the human growth hormone (GH) axis in Women by continuous 24-hour GHreleasing peptide infusion: pulsatile, entropic, and nyctohemeral mechanisms. J. Clin. Endocrinol. Metab. 84:2140-2150. https://doi.org/10.1210/jc.84.6.2140
  31. Shimon, I., X. Yan and S. Melmed. Human fetal pituitary express functional growth hormone-releasing peptide receptors. 1998. J. Clin. Endocrinol. Metab. 83:174-178. https://doi.org/10.1210/jc.83.1.174
  32. Sillence, M. N. and T. D. Etherton. 1987. Determination of the temporal relationship between porcine growth hormone, serum IGF-1 and cortisol concentrations in pigs. J. Anim. Sci. 64:1019-1023. https://doi.org/10.2527/jas1987.6441019x
  33. Thomas, G. B., P. A. Bennett, D. F. Carmignac and I. C. A. F. Robinson. 2000. Glucocorticoid regulation of growth hormone (GH) secretagogue-induced GH responses and GH secretagogue receptor expression in the rat. GH & IGF Res. 10:45-52. https://doi.org/10.1054/ghir.1999.0138
  34. Vance, M. L., D. L. Kaiser, P. M. Martha, R. Furlanetto, J. Rivier and W. Vale. 1989. Lack of in vivo somatotroph desensitization or depletion after 14 days of continuous growth hormone (GH)-releasing hormone administration in normal men and a GH-deficient boy. J. Clin. Endocrinol. Metab. 68:22-28. https://doi.org/10.1210/jcem-68-1-22
  35. Vanderkool, W. K., M. J. Vandehaar, B. K. Sharma, M. Binelli, H. A. Tucker, R. M. Akers and W. M. Moseley. 1995. Comparison of growth hormone-releasing factor and somatotropin: the somatotropic axis in lactating primiparous cows. J. Dairy Sci. 78:2140-2149. https://doi.org/10.3168/jds.S0022-0302(95)76841-2
  36. Wu, D., C. Chen, K. Katoh, J. Zeng and I. J. Clarke. 1994. The effect of GH-releasing peptide-2 (GHRP-2 or GHRP-2) on GH secretion from primary cultured ovine pituitary cells can be abolished by a specific GH-releasing factor (GRF) receptor antagonist. J. Endocrinol. 140:R9-R13. https://doi.org/10.1677/joe.0.140R009