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Growth Hormone Releasing Peptides

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Growth Hormone Secretagogues

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Abstract

Growth hormone releasing peptides (GHRP) are small peptides, having no sequence homology with growth hormone releasing hormone (GHRH) and characterized by high potency and selectivity in releasing growth hormone (GH). The best known series have been prepared and studied by Momany and Bowers (1). Their pioneering and outstanding research over several years has allowed the clinical development of promising compounds such as GHRP-6, GHRP-1, and GHRP-2 has spurred intense investigations on their mode of action and on analogues, including nonpeptides (Table 6.1).

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References

  1. Bowers CY. GH releasing peptides—structure and kinetics. J Pediar Endocrinol 1993;6:21–31.

    Article  CAS  Google Scholar 

  2. Bowers CY, Chang J, Momany F, Folkers K. Effect of the enkephalins and enkephalin analogues on release of pituitary hormones in vitro. In: Maclntyre and Szelke, editors. Molecular Endocrinology. Elsevier/North Holland Biomedical Press, 1977;287–92.

    Google Scholar 

  3. Bowers CY, Momany F, Reynolds GA, Chang D, Hong A, Chang K. Structure-activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro. Endocrinology 1980;106:663–7.

    Article  PubMed  CAS  Google Scholar 

  4. Momany FA, Bowers CY, Reynolds GA, Chang D, Hong A, Newlander K. Design, synthesis and biological activity of peptides which release growth hormone in vitro. Endocrinology 1981;108:31–9.

    Article  PubMed  CAS  Google Scholar 

  5. Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 1984;114:1537–45.

    Article  PubMed  CAS  Google Scholar 

  6. Ellinger A, Matsuoka. Preparation of [2]-methyltryptophan and its behaviour in the animal organism. Z Physiol Chem 1914;91:45–7.

    CAS  Google Scholar 

  7. Majima S. Ein biologisches Verfahren der d-Tryptophandarstellung. Hoppe Seylers Z Physiol Chem 1936;243:250–3.

    CAS  Google Scholar 

  8. Yabe Y, Miura C, Horikoshi H, Miyagawa H, Baba Y. Synthesis and biological activity of LH-RH analogues substituted by alkyltryptophans at position 3. Chem Pharm Bull 1979;27:1907–11.

    PubMed  CAS  Google Scholar 

  9. Deghenghi R, Boutignon F, Wuthrich P, Lenaerts V. EP23904 (Meterelin)—a novel sustained release LHRH-agonist. Gynecol Endocrinol 1993; 7:29 (abstr).

    Google Scholar 

  10. Deghenghi R, Cananzi MM, Torsello A, Battisti C, Miiller EE, Locatelli V. GH-releasing activity of hexarelin, a new growth hormone releasing peptide, in infant and adult rats. Life Sci 1994;18:1321–8.

    Article  Google Scholar 

  11. Conley LK, Giustina A, Imbimbo BP, Stagg LC, Deghenghi R, Wehrenberg WB. Hexarelin (His-D-2-MethylTrp-Ala-Trp-D-Phe-Lys-NH2): a new GH-releasing peptide, is biologically active in male and female rats. Endocr J 1994;2:691–5.

    CAS  Google Scholar 

  12. Bowman WC, Rand MJ. Textbook of pharmacology, 2nd ed. Oxford: Blackwell Scientific, 1980: 1612.

    Google Scholar 

  13. Walker RF, Codd EE, Yellin T, Fishman B. Growth hormone (GH) releasing activity and binding correlations following structural modification of a GH-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6; SK&F 110679). 71st Annual Meeting, The Endocrine Society, 1989; Abstract 777.

    Google Scholar 

  14. Blake AD, Smith RG. Desensitization studies using perfused rats pituitary cells show that growth hormone-releasing hormone and His-D-Trp-Ala-Trp-D-Phe- Lys-NH2 stimulate growth hormone release through distinct receptor sites. J Endocrinol 1991;129:11–19.

    Article  PubMed  CAS  Google Scholar 

  15. Chick CL, Akman M, Girard M, Ho AK. Growth hormone releasing peptide stimulates GH via a calcium-dependent c-AMP-independent mechanism. 74th Annual Meeting, The Endocrine Society 1992; Abstract 521.

    Google Scholar 

  16. Guillaume V, Magnan E, Catald M, Dutour A, Sauze N, Renard M, Razafindraibe H, Conte-Devolx B, Lenaerts V, Deghenghi R, Oliver C. GHRH secretion is stimulated by a new GHRP hexapeptide in sheep. Endocrinology 1994;135:1073–6.

    Article  PubMed  CAS  Google Scholar 

  17. Dickson SL, Leng G, Robinson ICAF. Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons. Neuroscience 1993;53:303–6.

    Article  PubMed  CAS  Google Scholar 

  18. Goth MI, Lyons CE, Canny BJ, Thorner MO. Pituitary adenyl cyclase activating polypeptide, GH-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. Endocrinology 1992;130:939–44.

    Article  PubMed  CAS  Google Scholar 

  19. Chihara K, Kaji H, Hayashi S, Yagi H, Takeshima Y, Mitami M, Ohashi S, Abe H. Growth hormone releasing hexapeptide: basic research and clinical application. In: Bercu BB, Walker RF, eds. Growth hormone II, basic and clinical aspects. New York: Springer-Verlag, 1994:223–30.

    Google Scholar 

  20. Bowers CY, Sartor AO, Reynolds GA, Badger TM. On the actions of growth hormone-releasing hexapeptide, GHRP. Endocrinology 1991;128:2027–35.

    Article  PubMed  CAS  Google Scholar 

  21. Sethumadhavan K, Veeraragavan K, Bowers CY. Demonstration and characterization of the specific binding of growth hormone-releasing peptide to rat anterior pituitary and hypothalamic membranes. Biochem Biophys Res Commun 1991;178:31–7.

    Article  PubMed  CAS  Google Scholar 

  22. Veeraragavan K, Sethumadhavan K, Bowers CY. Growth hormone releasing peptide (GHRP) binding to porcine anterior pituitary and hypothalamic membranes. Life Sci 1992;50:1149–55.

    Article  PubMed  CAS  Google Scholar 

  23. Codd EE, Shu AYL, Walker RF. Binding of a growth hormone releasing hexapeptide to specific hypothalamic and pituitary binding sites. Neuropharmacology 1989;28:1139–44.

    Article  PubMed  CAS  Google Scholar 

  24. Tannenbaum GS, Bowers CY. Growth hormone-releasing hexapeptide GHRP stimulates GH release via central GH-releasing factor (GRF) pathways. Society of Neuroscience Annual Meeting 1991; Abstract.

    Google Scholar 

  25. Locatelli V, Torsello A, Grilli R, Ghigo MC, Cella SG, Deghenghi R, Wehrenberg WB, Miiller EE. GHRP-6 stimulates GH secretion and synthesis independently from endogenous GHRH and SRIF in the infant rat. J Endocrinol Invest 1993;16:OP27(abstr).

    Google Scholar 

  26. Conley LK, Teik JA, Deghenghi R, Imbimbo BP, Giustina A, Locatelli V, Wehrenberg WB. The mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat. Neuroendocrinology 1995;61:44–50.

    Article  PubMed  CAS  Google Scholar 

  27. Clark RG, Carlsson LMS, Trojnar J, Robinson ICAF. The effects of a growth hormone-releasing peptide and GH-releasing factor in conscious and anaesthetized rats. J Endocrinol 1989;1:249–55.

    CAS  Google Scholar 

  28. Papageorgiou C, Haltiner R, Bruns C, Petcher TJ. Design, synthesis and binding affinity of a nonpeptide mimic of somatostatin. Biorg Med Chem Lett 1992;2:135–40.

    Article  CAS  Google Scholar 

  29. Sawyer TK, Staples DJ, De Lauro Castrucci AM, Hadley ME. Discovery and structure-activity relationships of novel a-melanocyte-stimulating hormone inhibitors. Peptide Res 1989;2:140–6.

    CAS  Google Scholar 

  30. Cheng K, Wei L, Chaung LY, Chan WWS, Butler B, Pong SS, Smith RG. Substance P antagonist inhibits L-692,429 and GHRP-6 stimulated rat growth hormone release both in vitro and in vivo. 76th Annual Meeting, The Endocrine Society 1994; Abstract 662.

    Google Scholar 

  31. Schoen WR, Ok D, DeVita RJ, Pisano JM, Hodges P, Cheng K, Chan WWS, Butler BS, Smith RG, Wyvratt MJ, Fischer MH. Structure-activity relationships in the amino acid sidechain of L-692,429. Bioorg Med Chem Lett 1994;9:1117–22.

    Article  Google Scholar 

  32. Schoen WR, Pisano JM, Prendergast K, Wyvratt MJ, Fischer MH, Cheng K, Chan WWS, Butler B, Smith RG, Ball RG. A novel 3-substituted benzazepinone growth hormone secretagogue (L-692,429). J Med Chem 1994;37:897–906.

    Article  PubMed  CAS  Google Scholar 

  33. Conley LK, Stagg LC, Giustina A, Imbimbo BP, Deghenghi R, Wehrenberg WB. Plasma GH responses are maintained following repeated doses and continuous infusions of hexarelin. 76th Annual Meeting, The Endocrine Society 1994; Abstract 659.

    Google Scholar 

  34. Chen K, Chan WWS, Barreto A, Convey EM, Smith RG. The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on GHRF-stimulated GH release and intracellular adenosine 3’,5’-monophosphate accumulation in rat primary pituitary cell culture. Endocrinology 1989;124:2791–8.

    Article  Google Scholar 

  35. Akman MS, Girard M, O’Brien LF, Ho AK, Chik CL. Mechanisms of action of a second generation growth hormone-releasing peptide (Ala-His-D-3Nal-Ala-Trp-D-Phe-Lys-NH2) in rat pituitary cells. Endocrinology 1993;132:1286–91.

    Article  PubMed  CAS  Google Scholar 

  36. Wu D, Chen C, Katoh K, Zhang J, Clarke IJ. 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 Endocrinol 1994;140:R9–R13.

    Article  PubMed  CAS  Google Scholar 

  37. Imbimbo BP, Mant T, Edwards M, Amin D, Dalton N, Boutignon F, Lenaerts V, Wiithrich P, Deghenghi R. Growth hormone-releasing activity of hexarelin in humans. Eur J Clin Pharmacol 1994;46:421–5.

    Article  PubMed  CAS  Google Scholar 

  38. Ghigo E, Arvat E, Giannotti L, Imbimbo BP, Lenaerts V, Deghenghi R, Camanni F. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal and oral administration in man. J Clin Endocrinol etab 1994;78:693–8.

    Article  CAS  Google Scholar 

  39. Tolis G, Mesimeris T, Deghenghi R, Boutignon F, Wiithrich P, Lenaerts V. Growth hormone release in thalassemic patients by a new GH-releasing peptide administered intravenous or orally. 75th Annual Meeting, The Endocrine Society 1993; Abstract 331.

    Google Scholar 

  40. Tolis G, Markusis V, Krassas G, Skaltsas T, Ponticidis J, Moschoyannis H, Boutignon F, Lenaerts V, Deghenghi R. Enhancement of hexarelin induced GH release by an inhibitor of lipolysis in women with polycystic ovarian syndrome. 76th Annual Meeting, The Endocrine Society, 1994; Abstract.

    Google Scholar 

  41. Loche S, Cambiaso P, Carta D, Setzu S, Casini MR, Imbimbo BP, Borrelli P, Pintor C, Cappa M. GH-releasing effect of hexarelin a new synthetic peptide, in short normal, GH-deficient and obese children. 76th Annual Meeting, The Endocrine Society 1994; Abstract.

    Google Scholar 

  42. Ghigo E, Arvat E, Gianotti L, DiVito L, Imbimbo B, Lenaerts V, Deghenghi R, Camanni F. Effects of hexarelin, a synthetic hexapeptide, alone and combined with GHRH or arginine on GH secretion in normal elderly subjects. 76th Annual Meeting, The Endocrine Society 1994; Abstract.

    Google Scholar 

  43. Arvat E, Ghigo E, Gianotti L, Maccario M, Procopio M, Grottoli S, Imbimbo BP, Lenaerts V, Deghenghi R, Camanni F. Neuroendocrinological and meta¬bolic modulation of the growth hormone-releasing activity of hexarelin in man. 76th Annual Meeting, The Endocrine Society 1994; Abstract.

    Google Scholar 

  44. Bellone J, Ghigo E, Aimaretti G, Benso L, Bartolotta E, Imbimbo BP, Deghenghi R, Camanni F. GH-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous administration in normal children. J Endocrinol Invest 1993;16(suppl 1–8).

    Google Scholar 

  45. Giustina A, Bussi AR, Deghenghi R, Imbimbo B, Licini H, Poiesi C, et al. Comparison of the effects of growth hormone-releasing hormone and hexarelin, a novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in humans with or without glucocorticoid excess. J Endocrinol 1995;146:227–32.

    Article  PubMed  CAS  Google Scholar 

  46. Casati G, Palmieri E, Biella O, Guglielmino L, Arosio M, Faglia G. Effects of hexarelin (EP23905-MF6003) on circulating GH, PRL, TSH gonadotropins and a-submit of glycoprotein hormone levels in acromegalic patients. 3rd European Congress of Endocrinology, Amsterdam 1994; Abstract.

    Google Scholar 

  47. Palmieri E, Casati G, Guglielmino L, Biella O, Gambino G, Arosio M, Faglia G. Effects of hexarelin on circulating PRL levels in normal subjects and in acromegalic patients. 3rd European Congress of Endocrinology, Amsterdam 1994; Abstract.

    Google Scholar 

  48. Giusti M, Porcella E, Imbimbo BP, Cuttica MC, Falivene MR, Sessarego P, Giordano G. PRL response to hexarelin in hyperprolactinaemic women: dopaminergic and opioid control on hexapeptide induced PRL release. 3rd International Congress of Neuroendocrinology. Budapest, 1994; Abstract.

    Google Scholar 

  49. Gould SJ. In the mind of the beholder. Natural History 1994;2:14–23.

    Google Scholar 

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Deghenghi, R. (1996). Growth Hormone Releasing Peptides. In: Bercu, B.B., Walker, R.F. (eds) Growth Hormone Secretagogues. Serono Symposia USA Norwell, Massachusetts. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2396-2_6

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  • DOI: https://doi.org/10.1007/978-1-4612-2396-2_6

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7526-8

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