Asian-Australasian Journal of Animal Sciences

  • 제15권5호
  • /
  • Pages.757-766
  • /
  • 2002
  • /
  • 1011-2367(pISSN)
  • /
  • 1976-5517(eISSN)
아세아태평양축산학회 (Asian Australasian Association of Animal Production Societies)
권호 표지
DOI QR코드

DOI QR Code

Characterization of Growth Hormone Secretion to Growth Hormone releasing Peptide-2 in Domestic Animals - A Review

  • Roh, Sang-Gun (Faculty of Agriculture, Shinshu University) ;
  • Lee, Hong-Gu (Dept of Animal Science and Technology, School of Agriculture and Life Science, Seoul National University) ;
  • Phung, Long Thang (Hue University of Agriculture and Forestry) ;
  • Hidari, Hisashi (Dept. of Animal Science, Obihiro University of Agriculture and Veterinary Medicine)
  • 발행 : 2002.05.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Growth hormone-releasing peptide-2 (GHRP-2, also named KP102) is a new hexapeptide of a series of synthetic growth hormone-releasing peptides (GHRPs) which stimulates the secretion of growth hormone (GH) in vitro and in vivo in several species including calf, sheep and pig. The GH-releasing activity of GHRP-2 is two to three times more effective than that of the original GHRP-6, and GHRP-1 in the rats and humans. To date, GHRP-2 seems to be the most potent member of the family of GHRPs. Since the GHRPs are short peptides (5-7 amino acid residues), they are synthesized easily and are not as readily degraded in plasma as GHreleasing hormone (GHRH). These features ameliorate their potential on domestic animals because of their chemical nature the GHRPs are efficacious when administered i.v. orally or orally. However, studies in cow, pig and sheep do not indicate such a close relationship between GHRH, somatostatin (SS) and GH, calling into question the general applicability of the human and rat models. Perhaps there is an important role for an endogenous GHRP in the regulation of GH secretion in domestic animals. This review provides an overview on the current knowledge of physiological role of GHRP-2 in domestic animals.

키워드

참고문헌

  1. Armstrong, J. D., W. S Cohick, R. W. Harvey, E. P. Heimer and R. M. Campbell. 1993. Effect of feed restriction on serum somatotropin, insulin-like growth factor-I-(IGF-I) and IGF binding proteins in cyclic heifers actively immunized against growth hormone releasing factor. Domest. Anim. Endocrinol. 10:315-324. https://doi.org/10.1016/0739-7240(93)90035-A
  2. Badger, T. M., W. J. Millard, G. F. McCormick, C. Y. Bowers and J. B. Martin. 1984. The effects of growth hormone(GH)-releasing peptides on GH secretion in perifused pituitary cells of adult male rats. Endocrinology 115:1432-1438. https://doi.org/10.1210/endo-115-4-1432
  3. Baker, P. K., S. D. Conner, M. E. Doscher, L. A. Kraft and C. A. Ricks. 1984. Use of a synthetic growth hormone releasing hexapeptide to increase rate of gain in rats. J. Anim. Sci. 59(Suppl.):220(Abstr.).
  4. Bowers, C. Y., D. K. Alster and J. M. Frentz. 1992. The growth hormone-releasing activity of a synthetic hexapeptide in normal men and short statured children after oral administration. J. Clin. Endocrinol. Metab. 74:292-298. https://doi.org/10.1210/jc.74.2.292
  5. Bowers, C. Y., F. A. Momany, G. A. Reynolds and A. Hong. 1984. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 114:1537-1545. https://doi.org/10.1210/endo-114-5-1537
  6. Bowers, C. Y., G. A. Reynolds, D. Durham, C. M. Barrera, S. S. Pezzoli and M. O. Thorner. 1990. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J. Clin. Endocrinol. Metab. 70:975-982. https://doi.org/10.1210/jcem-70-4-975
  7. Bowers, C. Y., A. O. Sartor, G. A. Reynolds and T. M. Badger. 1991. On the actions of the growth hormone-releasing hexapeptide, GHRP. Endocrinology 128:2027-2035. https://doi.org/10.1210/endo-128-4-2027
  8. Bowers, C. Y. 1993. GH releasing peptides-structure and kinetics. J. Pediatr. Endocrinol 6:21-31.
  9. Buonomo, F. C. and C. A. Baile. 1990. The neurophysiological regulation of growth hormone secretion. Domest. Anim. Endocrinol. 7:435-450. https://doi.org/10.1016/0739-7240(90)90001-G
  10. Camacho-Hubner, C., R. H. McCusker and D. R. Clemmons. 1991. Secretion and biological actions of insulin-like growth factor binding proteins in two human tumor-derived cell lines in vitro. J. Cell Physiol. 148:281-9. https://doi.org/10.1002/jcp.1041480214
  11. Chen, C., D. Wu and I. J. Clark. 1996. Signal transduction systems employed by synthetic GH-releasing peptides in somatotrophs. J. Endocrinology 148:381-386. https://doi.org/10.1677/joe.0.1480381
  12. Cheng, K., W. W. -S. Chan, B. Butler, L. Wei, W. R. Schoen, M. J. Jr. Wyvratt, M. H. Fisher and R. G. Smith. 1993. Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl GH secretagogue Endocrinology 132(6):2729-2731. https://doi.org/10.1210/en.132.6.2729
  13. Cheng, K., W. W. -S. Chan, A. Jr. Barreto, E. M. Convey and R. G. Smith. 1989. The synergistic effects of His-D-Trp-Ala-Trp-DPhe-Lys-NH2 on growth hormone (GH)-releasing factorstimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture. Endocrinology 124:2791-2798. https://doi.org/10.1210/endo-124-6-2791
  14. Clark, R. G., L. M. S. Carlsson, J. Trojnar, and I. C. A. F. Robinson. 1989. The effect of a growth hormone-releasing peptide and growth hormone-releasing factor in conscious anaesthetized rats. J. Neuroendocrinology 1:249-255. https://doi.org/10.1111/j.1365-2826.1989.tb00112.x
  15. Codd, E. E., A. Y. L. Shu and R. F. Walker. 1989. Binding of a growth hormone releasing hexapeptide to specific hypothalamus and pituitary binding sites. Neuropharmacology 28:1139-1144. https://doi.org/10.1016/0028-3908(89)90129-9
  16. Cohick, W. S., J. D. Armstrong, M. D. Whitacre, M. C. Lucy, R. W. Harvey and R. M. Campbell. 1996. Ovarian expression of insulin-like growth factor-I (IGF-I), IGF binding proteins, and growth hormone (GH) receptor in heifers actively immunized against GH-releasing factors. Endocrinology 137:1670-1677. https://doi.org/10.1210/en.137.5.1670
  17. Cohick, W. S., M. A. McGuire, D. R. Clemmons and D. E. Bauman. 1992. Regulation of insulin-like growth factorbinding proteins in serum and lymph of lactating cows by somatotropin. Endocrinology 1992;130:1508-1514. https://doi.org/10.1210/en.130.3.1508
  18. Cohick, W. S., K. Plaut, S. J. Sechen and D. E. Bauman. 1989. Temporal pattern of insulin-like growth factor-1 response to exogenous bovine somatotropin in lactating cows. Domest. Anim. Endocrinol. 6:263-273. https://doi.org/10.1016/0739-7240(89)90020-9
  19. Conley, L. K., J. A. Teik, R. Deghenghi, B. P. Imbimbo, A. Guistina, V. Locatelli and W. B. Wehrenberg. 1995. Mechanism of action of hexarelin and GHRP-6 : Analysis of the involvement of GRF and somatostatin in the rat. Neuroendocrinology 61:44-50. https://doi.org/10.1159/000126826
  20. Conway, S., L. Richardson, S. Speciale, R. Moherek, H. Mauceri and L. Krulich. 1990. Interaction between norepinephrine and serotonin in the neuroendocrine control of groth homorne release in the rat. Endocrinology 126:1022-1030. https://doi.org/10.1210/endo-126-2-1022
  21. Debell, W. K., S. S. Pezzoli and M. O. Thorner. 1991. Growth hormone (GH) secretion during continuous infusion of GHreleasing peptide: partial response attenuation. J. Clin. Endocrinol. Metab. 72:1312-1316. https://doi.org/10.1210/jcem-72-6-1312
  22. Della-Fera, M. A., F. C. Buonomo and C. A. Baile. 1986. Growth hormone secretory responsiveness to multiple injections of growth hormone-releasing factor in sheep. Domest. Anim. Endocrinol. 3:153-164. https://doi.org/10.1016/0739-7240(86)90003-2
  23. Dickson, S. L., G. Leng, R. E. Dyball and R. G. Smith. 1995. Central actions of peptide and non-peptide growth hormone secretagogues in the rat. Neuroendocrinology 61:36-43. https://doi.org/10.1159/000126825
  24. Doscher, M. E., P. K. Baker, L. A. Kraft and C. A. Ricks. 1984. Effects of a synthetic growth hormone releasing hexapeptide (BI 679) and growth hormone releasing factor (GRF) on serum growth hormone levels in barrows. J. Anim. Sci. 59(Suppl.):218(Abstr.).
  25. 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.
  26. Enright, W. J., L. T. Chapin, W. M. Moseley, S. A. Zinn, M. B. Kamdar, L. F. Krabill and H. A. Tucker. 1989. Effects of infusions of various doses of bovine growth hormone-releasing factor on blood hormones and metabolites in lactating Holstein cows. J. Endocrinology 122:671-679. https://doi.org/10.1677/joe.0.1220671
  27. Fletcher, T. P., G. B. Thomas and I. J. Clarke. 1996. Growth hormone-releasing hormone and somatostatin concentrations in the hypophysial portal blood of conscious sheep during the infusion of growth hormone-releasing peptide-6. Domest. Anim. Endocrinol. 13:251-256. https://doi.org/10.1016/0739-7240(96)00017-3
  28. Fletcher, T. P., G. B. Thomas, J. O. Willoghby and I. J. Clarke. 1994. Constitutive growth hormone secretion in sheep after hypothalamopituitary disconnection and the direct in vivo pituitary effect of growth hormone releasing peptide 6. Neuroendocrinology 60:76-86. https://doi.org/10.1159/000126722
  29. Frohman, L., T. Downs, I. Clark I and G. Thomas. 1990. Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep: Spontaneous secretion and response to insulin-induced hypoglycemia. J. Clin. Invest. 86:17-24. https://doi.org/10.1172/JCI114681
  30. Gallaher, B. W., B. H. Breier, W. F. Blum, S. N. McCutcheon and P. D. Gluckman. 1995. A homologous radioimmunoassay for ovine insulin-like growth factor-binding protein-2: Ontogenesis and the response to growth hormone, placental lactogen and insulin-like growth factor-1 treatment in sheep. J. Endocrinology 144:75-82. https://doi.org/10.1677/joe.0.1440075
  31. Gallaher, B. W., B. H. Breier, M. H. Oliver, J. E. Harding and P. D. Gluckman. 1992. Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma. Acta Endocrinol. 126:49-54.
  32. Gaynor, P. J., C. R. Simmons, K. J. Lookingland and H. A. Tucker. 1996. 5-hydroxytryptaminergic receptor-mediated regulation of growth hormone secretion in Holstein steers occurs via a2-adrenergic-dependent and -independent mechanisms. Proc. Soc. Exp. Biol. Med. 212:355-361.
  33. Gertz, B. J., J. S. Barrett, R. Eisenhandler, D. A. Krupa, J. M. Wittreich, J. R. Seibold and S. H. Schneider. 1993. Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.J. Clin. Endocrinol. Metab. 77:1393-1397. https://doi.org/10.1210/jc.77.5.1393
  34. Ghigo, E., E. Arvat, L. Gianotti, B. P. Imbimbo, V. Lenaerts, R. Deghenghi and F. Camanni. 1994. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. J. Clin. Endocrinol. Metab. 78:693-698. https://doi.org/10.1210/jc.78.3.693
  35. Ghigo, E., E. Arvat, G. Rizzi, S. Goffi, S. Grottoli, M. Mucci, M. F. Boghen and F. Camanni. 1994. Growth hormone releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging. Eur. J. Endocrinol. 131:499-503. https://doi.org/10.1530/eje.0.1310499
  36. Ghigo, E., E. Arvat, L. Gianotti, S. Grottoli, G. Rizzi, G. P. Ceda, M. F. Boghen, R. Deghenghi and F. Camanni. 1996. Shortterm administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging. Eur. J. Endocrinol. 135:407-412. https://doi.org/10.1530/eje.0.1350407
  37. Goth, M. I., C. E. Lyons, B. J. Canny and M. O. Thorner. 1992. Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct receptors. Endocrinology 130:939-944. https://doi.org/10.1210/en.130.2.939
  38. Guler, H. P, J. Zapf, C. Schmid and E. R. Froesch. 1989. Insulinlike growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinol. 121:753-758.
  39. Hart, I. C., P. M. E. Chadwick, A. Coert, S. James and A. D. Simmonds. 1985. Effect of different growth hormone-releasing factors on the concentrations of growth hormone, insulin and metabolites in the plasma of sheep maintained in positive and negative energy balance. J. Endocrinology 105:113-119. https://doi.org/10.1677/joe.0.1050113
  40. Hartman, M. L., G. Farello, S. S. Pezzoli and M. O. Thorner. 1992. Oral administration of growth hormone (GH)-releasing peptide stimulates GH secretion in normal men. J. Clin. Endocrinol. Metab. 74:1378-1384. https://doi.org/10.1210/jc.74.6.1378
  41. Hashizume, T., M. Kawai, K. Ohtsuki, A. Ishii and M. Numata. 1999. Oral administration of peptidergic growth hormone (GH) secretagogue KP102 stimulates GH release in goats. Domest. Anim. Endocrinol. 16:31-39. https://doi.org/10.1016/S0739-7240(98)00048-4
  42. Hashizume, T., K. Sasaki, M. Sakai, S. Tauchi and H. Masuda. 1997a. The effect of new growth hormone–releasing peptide (KP102) on the release of growth hormone in goats. Anim. Sci. Technol. (Japan) 68:247-256.
  43. Hashizume, T., M. Yanagimoto, S. Kainuma, R. Nagano, K. Moriwaki, K. Ohtsuki, K. Sasaki, H. Masuda and T. Hirata. 1997b. Effect of new growth hormone–releasing peptide (KP102) on the release of growth hormone in vitro and in vivo in cattle. Anim. Sci. Technol. (Japan) 68:450-458.
  44. Hickey, G., T. Jacks, F. Judith, J. Taylor, W. R. Schoen, D. Krupa, P. Cunningham, J. Clark and R. G. Smith. 1994. Efficacy and specificity of L-692,429, a novel nonpeptidyl growth hormone secretagogue in beagles. Endocrinology 134:695-701. https://doi.org/10.1210/en.134.2.695
  45. Hodgkinson, S. C., J. J. Bass and P. D. Gluckman. 1991. Plasma IGF-1 binding proteins in sheep: effect of recombinant growth hormone treatment and nutritional status. Domest. Anim. Endocrinol. 8:343-351. https://doi.org/10.1016/0739-7240(91)90002-2
  46. Howard, A. D., S. D. Feighner, D. F. Cully, J. P. Arena, P. A. Liberator, C. I. Rosenblum, M. Hamelin, D. L. Hreniuk, O. C. Palyha, J. Anderson, P. S. Paress, C. Diaz, M. Chou, K. K. Liu, K. K. McKee, S. S. Pong, L. Y. Chaung, A. Elbrecht, M. Dashkevicz, R. Heavens, M. Rigby, D. J. S. Sirinathsinghii, D. C. Dean, D. G. Melillo, A. A. Patchett, R. Nargund, P. R. Griffin, J. A. DeMartino, S. K. Gupta, J. M. Schaeffer, R. G. Smith and L. H. T. Van der Ploeg. 1996. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974-977. https://doi.org/10.1126/science.273.5277.974
  47. Huhn, W. C., M. L. Hartman, S. S. Pezzoli and M. O. Thorner. 1993. Twenty-four-hour growth hormone (GH)-releasing peptide (GHRP) infusion enhances pulsatile GH secretion and specifically attenuates the response to a subsequent GHRP bolus. J. Clin. Endocrinol. Metab. 76:1202-1208. https://doi.org/10.1210/jc.76.5.1202
  48. Jacks, T., G. Hickey, F. Judith, J. Taylor, H. Chen, D. Krupa, W. Feeney, W. Schoen, D. Ok, M. Fisher, M. Wyvratt and R. Smith. 1994. Effects of acute and repeated intravenous of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-I, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles. J. Endocrinology 143:399-406. https://doi.org/10.1677/joe.0.1430399
  49. Jaffe, C. A., P. J. Ho, R. Demott-friberg, C. Y. Bowers and A. L. Barkan. 1993. Effects of a prolonged growth hormone (GH)-releasing peptide infusion on pulsatile GH secretion in normal men. J. Clin. Endocrinol. Metab. 77:1641-1647. https://doi.org/10.1210/jc.77.6.1641
  50. Johnson, D. W., M. A. Barner, R. M. Akers and R. E. Pearson. 1993. A synthetic opioid peptide increases plasma growth hormone and prolactin in Holstein calves. J. Anim. Sci. 71:1004-1009.
  51. Kirby, C. J., J. D. Armstrong, B. G. Huff, R. L. Stanko, R. W. Harvey, E. P. Heimer and R. M. Campbell. 1993. Changes in serum somatotropin, somatotropin mRNA, and serum and follicular insulin-like growth factor-I in response to feed restriction in cows actively immunized against growth hormone-releasing factor. J. Anim. Sci. 71:3033-3042.
  52. Kojima, M., H. Hosoda, Y. Date, M. Nakazato, H. Matsuo and K. Kangawa. 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660. https://doi.org/10.1038/45230
  53. Kraft, L. A., P. K. Baker, M. E. Doscher and C. A. Ricks. 1984. Effects of a synthetic growth hormone releasing hexapeptide on serum growth hormone levels in steers. J. Anim. Sci. 59(Suppl.):218(Abstr.).
  54. Lau, Y. S., A. M. Camoratto, L. M. White and C. M. Moriartu. 1991. Effect of lead on TRH and GRF binding in rat anterior pituitary membranes. Toxicology 68:169-179. https://doi.org/10.1016/0300-483X(91)90019-W
  55. Lee, H. G., R. A. Vega, L. T. Phung, N. Matsunaga, H. Kuwayama and H. Hidari. 2000. The effect of growth hormone-releasing peptide-2 (KP102) 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
  56. Locatelli, V., A. Tosello, M. Readaelli, E. Ghigo, F. Massara and E. E. Muller EE. 1986. Cholinergic agonist drugs modulate the growth hormone response to growth hormone releasing hormone in the rats: evidence fro mediation by somatostatin. J. Endocrinology 111:271-275. https://doi.org/10.1677/joe.0.1110271
  57. Locke, W., H. D. Kirgis, C. Y. Bower and A. A. Abdoh. 1995. Intracerebroventricular growth hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats. Life Sci. 56:1347-1352. https://doi.org/10.1016/0024-3205(95)00087-9
  58. Masuda, Y., T. Tanaka, N. Inomata, N. Ohnuma, S. Tanaka, Z. Itoh, H. Hosoda, M. Kojima and K. Kangawa. 2000. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem. Biophys. Res. Commun. 276:905-908. https://doi.org/10.1006/bbrc.2000.3568
  59. McFadden, T. B., T. E. Daniel and R. M. Akers. 1990. Effects of plane of nutrition, growth hormone and unsaturated fat on growth hormone, insulin and prolactin receptors in prepubertal lambs. J. Amin. Sci. 68:3180-3189.
  60. McMahon, C. D., L. T. Chapin, K. J. Lookingland, R. P. Radcliff and H. A. Tucker. 1999. Feeding-induced increases in insulin do not suppress secretion of growth hormone. Domest. Anim. Endocrinol. 17:439-447. https://doi.org/10.1016/S0739-7240(99)00050-8
  61. Momany, F. A., C. Y. Bowers, G. A. Reynolds, A. Hong and K. Newlander. 1984. Conformational energy studies and in vitro and in vivo activity data on growth hormone-releasing peptides. Endocrinology 114:1531-1536. https://doi.org/10.1210/endo-114-5-1531
  62. Moseley, W.M., G.R. Alaniz, W.H. Claflin, and L.F. Krabill. 1988. Food intake alters serum growth hormone response to bovine growth hormone-releasing factor in meal-fed Holstein steers. J. Endocrinology 117:253-259. https://doi.org/10.1677/joe.0.1170253
  63. Murakami, Y., K. Kato, Y. Kabayama, K. Tojo, T. Inoue and H. Imura. 1986. Involvement of growth hormone (GH)-releasing factor in GH secretion induced by serotonergic mechanisms in conscious rats. Endocrinology 119:1089-1092. https://doi.org/10.1210/endo-119-3-1089
  64. Muruais, J., A. Penalva, C. Dieguez and F. F. Casanueva. 1993. Influence of endogenous cholinergic tone and a-adrenergic pathways on growth hormone responses to His-D-Trp-Ala-Trp-D-Phe-Lys-$NH_2$ in the dog. J. Endocrinology 138:211-218. https://doi.org/10.1677/joe.0.1380211
  65. Muller, E. 1987. Neural control of somatotropic function. Physiol. Rev. 67:962-1053.
  66. Newbold, J. A., R. B. Heap, C. G. Prosser, R. H. Phipps, F. Adriaens and D. L. Hard. 1997. The effect of bovine somatotropin and diet on somatotropin binding sites in hepatic tissue of lactating dairy cows. J. Dairy Sci. 80:1085-1091. https://doi.org/10.3168/jds.S0022-0302(97)76033-8
  67. Nijland, E. A., C. J. Strasburger, C. Popp-Snijders, P. S. Van der Wal and E. A. Van der Veen. 1998. A five day treatment with daily s.c. injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-1 secretion in healthy young men. Eur. J. Endocrinol. 139:395-401. https://doi.org/10.1530/eje.0.1390395
  68. Okada, K., S. Ishii, S. Minami, T. Shibasaki and I. Wakabayashi. 1996. Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats. Endocrinology 137:5155-5158. https://doi.org/10.1210/en.137.11.5155
  69. Patchett, A. A., R. P. Nargund, J. R. Tata, M. H. Chen, K. J. Barakat, D. B. Johnston, K. Cheng, W. W. Chan, B. Butler and G. Hickey. 1995. Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc. Natl. Acad. Sci. 92(15):7001-7005. https://doi.org/10.1073/pnas.92.15.7001
  70. Petitclerc, D., G. Pelletier, H. Lapierre, P. Gaudreau, Y. Couture, P. Dubreuil, J. Morisset and P. Brazeau. 1987. Dose response of two synthetic human growth hormone-releasing factors on growth hormone release in heifer and pigs. J. Anim. Sci. 65:996-1005.
  71. Penalva, A., A. Carballo, M. Pombo, E. F. Casanueva and C. Dieguez C. 1993. Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. J. Clin. Endocrinol. Metab. 76:168-171. https://doi.org/10.1210/jc.76.1.168
  72. Phung, L. T., A. Sasaki, H. G. Lee, R. A. Vega, N. Matsunaga, S. Hidaka, H. Kuwayama and H. Hidari. 2001. Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed ongrowth hormone release in swine. Domest. Anim. Endocrinol. 20:9-19. https://doi.org/10.1016/S0739-7240(00)00085-0
  73. 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 releasing of growth hormone and growth performance in swine. Domest. Anim. Endocrinol 18:279-291. https://doi.org/10.1016/S0739-7240(00)00050-3
  74. Pong, S. S., L. Y. P. Chaung, D. C. Dean, R. P. Nargund, A. A. Patchett and R. G. Smith. 1996. Identification of a new Gprotein linked receptor for growth hormone secretagogues. Mol. Endocrinol. 10:57-61. https://doi.org/10.1210/me.10.1.57
  75. Rajaram, S., D. J. Baylink and S. Mohan. 1997. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocrine Review 18:801-831. https://doi.org/10.1210/er.18.6.801
  76. Rigamonti, A. E., S. G. Cella, N. Marazzi and E. E. Muller. 1999. Six-week treatment with hexarelin in young dogs: evaluation of the GH responsiveness to acute hexarelin or GHRH administration, and of the orexigenic effect of hexarelin. Eur. J. Endocrinology 41:313-320. https://doi.org/10.1530/eje.0.1410313
  77. Roberts, A. J., R. A. Nugent, J. Klindt and T. G. Jenkins. 1997. Circulating insulin-like growth factor I, insulin-like growth factor binding proteins, growth hormone, and resumption of estrus in postpartum cows subjected to dietary energy restriction. J. Anim. Sci. 75:1909-1917.
  78. Roh, S. G., M. L. He, N. Matsunaga, S. Hidaka and H. Hidari. 1997a. Mechanisms of action of growth hormone-releasing peptide-2 in bovine pituitary cells. J. Anim. Sci. 75:2744-2748.
  79. Roh, S. G., M. L. He, N. Matsunaga, S. Hidaka and H. Hidari. 1997b. No desensitization of the growth hormone (GH) response between GH-releasing peptide-2 and GH-releasing factor in calves. J. Anim. Sci. 75:2749-2753.
  80. Roh, S. G., M. Hirota, M. L. He, N. Matsunaga, S. Hidaka and H. Hidari. 1997c. Effects of muscarinic and adrenergic blockade on growth hormone secretion induced by growth hormonereleasing hormone (GHRP-2) in ovariectomized ewes. Endocrine J. 44:861-865. https://doi.org/10.1507/endocrj.44.861
  81. 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
  82. Ross, R. J., M. Tsagarakis, A. Grossman and G. M. Besser. 1987. GH feed-back occurs through modulation of hypothalalmic somatostatin under cholinergic control:studies with pyridostigmine and GHRH. Clinical Endocrinology 27:727- 732. https://doi.org/10.1111/j.1365-2265.1987.tb02957.x
  83. Sartin, J. L., R. J. Kemppainen, D. N. Marple, R. Varnes, G. Dieberg and E. H. Oliver. 1987. Effects of parachlorophenylalanine, quipazine and cyproheptadine on growth hormone and adrenocorticotropin secretion in steers. Domest. Anim. Endocrinol. 4:33-41. https://doi.org/10.1016/0739-7240(87)90036-1
  84. Sartor, O., C. Y. Bowers, G. A. Reynolds and F. A. Momany. 1985. Variables determining the growth hormone response of His-D-Trp-Ala-Trp-D-Phe-Lys-$NH_2$ in the rat. Endocrinology 117:1441-1447. https://doi.org/10.1210/endo-117-4-1441
  85. Sawada, H., H. Sugihara, H. Onose, S. Minami, T. Shibasaki and I. Wakabayashi. Effect of D-Ala-D-$\beta$Nal-Ala-Trp-D-Phe-Lys-$\NH_2$ (KP-102) on GH secretion in urethan-anesthetized rats. Regul. Peptides 53:195-201. https://doi.org/10.1016/0167-0115(94)90168-6
  86. Simpson, R. B., J. D. Armstrong and R. W. Harvey. 1992. Effect of prepartum administration of growth hormone releasing factor on somatotropin, insulin-like growth factor I, milk production and postpartum return to ovarian activity in primiparous beef heifers. J. Anim. Sci. 70:1478-1487.
  87. Smith, R. G., K. Cheng, W. R. Schoen, S. S. Pong, G. Hickey, T. Jacks, B. Butler, W. W. Chan, L. Y. Chaung and F. Judith et al. 1993. A nonpeptidyl growth hormone secretagogue. Science. 260:1640-1643. https://doi.org/10.1126/science.8503009
  88. Torsello, A., M. Luoni, F. Schweiger, R. Grilli, M. Guidi, E. Bresciani, R. Deghenghi, E. E. Muller and V. Locatelli. 1998. Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. Eur. J. Pharmacol. 360:123-129. https://doi.org/10.1016/S0014-2999(98)00677-3
  89. Trenkle, A. 1998. Influence of feeding on growth hormone secretion and response to growth hormone-releasing factor in sheep. J. Nutr. 1989;119:61-65.
  90. Van den Berghe, G., P. Wouters, C. Y. Bowers and F. de Zegher. 1999. R. Bouillon. Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness. Eur. J. Endocrinol. 140:17-22. https://doi.org/10.1530/eje.0.1400017
  91. Vicini, J. L., F. C. Buonomo, J. J. Veenhuizen, M. A. Miller, D. R. Clemmons and R. J. Collier. 1991. Nutrient balance and stageof lactation affect responses of insulin, insulin like growth factors 1 and 2, and insulin-like growth factor-binding protein 2 to somatotropin administration in dairy cows. J. Nutr. 121:1656-1664.
  92. Walker, R. F., E. E. Cold, F. C. Barone, A. H. Nelson, T. Goodwin and S. A. Campbell. 1990. Oral activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-$NH_2$ in rats, dogs and monkeys. Life Sci. 47:29-36. https://doi.org/10.1016/0024-3205(90)90563-7
  93. Willoughby, J. O., M. F. Menadue and H. Liebelts. 1987. Activation of serotonin receptors in the medial basal hypothalamus stimulates growth hormone secretion in the unanesthetized rat. Brain Res. 404:319-322. https://doi.org/10.1016/0006-8993(87)91386-2
  94. Wu, D., C. Chen, K. Katoh, J. Zhang and I. J. Clarke. 1994a. The effect of GH-releasing peptide-2 (GHRP-2 or KP102) on GH secretion from primary cultured ovine pituitary cells can be abolished by a specific GH-releasing factor (GRF) receptor antagonist. J. Endocrinology 140:R9-13. https://doi.org/10.1677/joe.0.140R009
  95. Wu, D., C. Chen, K. Katoh, J. Zhang and I. J. Clarke. 1994b. Effects in vitro of growth hormone-releasing factor (GRF) and growth hormone releasing peptide (GHRPs) on growth hormone secretion from ovine pituitary cells in primary culture. J. Neuroendocrinology 6:185-190. https://doi.org/10.1111/j.1365-2826.1994.tb00571.x
  96. Wu, D., C. Chen, J. Zhang, C. Y. Bowers and I. J. Clarke. 1996. The effects of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on intracellular adenosine 3',5'-monophosphate (cAMP) levels and GH secretion in ovine and rat somatotrophs. J. Endocrinology 148:197-205. https://doi.org/10.1677/joe.0.1480197