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Neural Control of Growth Hormone Secretion in Aged Humans

  • E. Ghigo
  • E. Arvat
  • S. Goffi
  • J. Bellone
  • M. Nicolosi
  • M. Procopio
  • M. Maccario
  • F. Camanni

Abstract

It is widely accepted that growth hormone (GH) secretion undergoes an age-related decrease in both animals and humans (Dieguez et al. 1988 Müller and Nisticò 1989). Twenty-four-hour integrated GH concentrations have been shown to be lower in older versus younger subjects (Zadik et al. 1985). More recently, the study of the 24-h GH profile with frequent sampling techniques demonstrated that both day-time and night-time mean pulse amplitude and duration but not pulse frequency are reduced in aged humans (Vermeulen 1987; Van Coervorden et al. 1991). On the contrary, other authors (Iranmanesh et al. 1991) found significant reductions in GH secretory burst frequency and half-life but not in GH secretory burst half duration, amplitude or mass. Interestingly, though both slow wave sleep and nocturnal GH secretion are drastically reduced in the elderly, the small GH rises during sleep are nevertheless temporally related to slow wave stages (Van Coervorden et al. 1991).

Keywords

Growth Hormone Exogenous Growth Hormone Normal Elderly Subject Growth Hormone Rise Spontaneous Growth Hormone Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Alba-Roth J, Muller OA, Schopohl J, Von Werder K (1988) Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab 67:1186–1189.PubMedCrossRefGoogle Scholar
  2. Bando H, Zhang C, Takada y, yamasaki R, Saito S (1991) Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men. Acta Endocrinol (Copenh) 124:31–36.Google Scholar
  3. Barthus RT, Dean RL, Beer B (1982) The cholinergic hypothesis of geriatric memory disfunction. Science 217:408–417.CrossRefGoogle Scholar
  4. Bowers CY, Alster DK, Frentz JM (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.PubMedCrossRefGoogle Scholar
  5. Casanueva FF, Villanueva L, Dieguez C (1986) Atropine blockade of growth hormone (GH)-releasing hormone-induced GH secretion in man is not exerted at pituitary level. J Clin Endocrinol Metab 62:186–189.PubMedCrossRefGoogle Scholar
  6. Ceda GP, Valenti G, Butturini U, Hoffman AR (1986) Diminished pituitary responsiveness to growth hormone-releasing factor in aging male rats. Endocrinology 118:2109–2114.PubMedCrossRefGoogle Scholar
  7. Clemmons DR, Van Wyk JJ (1984) Factors controlling blood concentration of somatomedin C. J Clin Endocrinol Metab 13:113–120.CrossRefGoogle Scholar
  8. Corpas E, Harman SM, Piñeyro M, Roberson R, Blackman MR (1992) Growth hormone (GH)-releasing hormone twice daily reverses the decreased GH and IGF-I levels in old man. J Clin Endocrinol Metab 75:530–535.PubMedCrossRefGoogle Scholar
  9. Coyle JT, Singer H, MacKinney M, Price D (1984) Neurotransmitter specific alteration in dementing disorders: Insight from animal models. J Psychiatr Res 18:501–512.PubMedCrossRefGoogle Scholar
  10. De Gennaro Colonna V, Zoli M, Cocchi D (1989) Reduced growth hormone releasing factor (GHRH)-like immunoreactivity and GHRH gene expression in hypothalamus of aged rats. Peptides 10:705–709.CrossRefGoogle Scholar
  11. Dieguez C, Page MD, Scanlon MF (1988) Growth hormone neuroregulation and its alterations in disease states. Clin Endocrinol (Oxf) 28:109–121.Google Scholar
  12. Dudl RJ, Ensinck JW, Palmer HE, Williams RH (1973) Effect of age on growth hormone secretion in man. J Clin Endocrinol Metab 37:11–16.PubMedCrossRefGoogle Scholar
  13. Ge F, Tsagarakis S, Rees LH, Besser GM, Grossman A (1989) Relationship between growth hormone-releasing hormone and somatostatin in the rat: effects of age and sex on content and in-vitro release from hypothalamic explants. J Endocrinol 123:53–58.PubMedCrossRefGoogle Scholar
  14. Ghigo E, Goffi S, Arvat E, Nicolosi M, Procopio M, Bellone J, Imperiale E, Mazza E, Baracchi G, Camanni F (1990a) Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging. Acta Endocrinol (Copenh) 123:169–174.Google Scholar
  15. Ghigo E, Goffi S, Nicolosi M, Arvat E, Bellone J, Procopio M, Valente F, Mazza E, Ghigo MC, Camanni F (1990b) Growth hormone (GH) responsiveness to combined administration of arginine and GH-releasing hormone does not vary with age in man. J Clin Endocrinol Metab 71:1481–1485.PubMedCrossRefGoogle Scholar
  16. Ghigo E, Arvat E, Goffi S, Bellone J, Valente F, Procopio M, Ghigo MC, Camanni F (1991a) Repetitive GHRH and arginine administration to explore the maximal secretory capacity of somatotroph cells during lifespan. Exp Clin Endocrinol (Life Sci Adv) 10:191–198.Google Scholar
  17. Ghigo E, Arvat E, Valente F, Nicolosi M, Boffano GM, Procopio M, Bellone J, Maccario M, Mazza F, Camanni F (1991b) Arginine reinstates the somatotrope responsiveness to intermittent Growth Hormone-Releasing Hormone administration in normal adults. Neuroendocrinology 54:291–295.PubMedCrossRefGoogle Scholar
  18. Ghigo E, Goffi S, Arvat E, Imperiale I, Boffano GM, Valetto MR, Mazza E, Santi I, Magliona A, Boghen MF, Boccuzzi G, Camanni F (1992) A neuroendocrinological approach to evidence an impairment of central cholinergic function in aging. J Endocrinol Invest 15: 665–670.PubMedGoogle Scholar
  19. Gibson GE, Peterson C, Jender DJ (1981) Brain acetylcholine synthesis declines with senescence. Science 213:675–678.CrossRefGoogle Scholar
  20. Gil-Ad I, Gurewitz R, Marcovici O, Rosenfeld J, Laron Z (1984) Effects of aging on human plasma growth hormone response to clonidine. Mech Ageing Dev 27:97–100.PubMedCrossRefGoogle Scholar
  21. Giusti M, Giovale M, Grossman A, Marini G, Drago T, Uggias B, Pompei A, Sessarego P, Delitala G (1992) Opioid analogue met-enkephalin does not potentiate GH release after GHRH in elderly men. J Endocrinol Invest 15[Suppl 4]:119.Google Scholar
  22. Hartman ML, Farello G, Pezzoli SS, Thorner MO (1992) Oral administration of growth hormone (GH)-releasing peptide stimulates GH secretion in normal men. J Clin Endocrinol Metab 74:1378–1384.PubMedCrossRefGoogle Scholar
  23. Iovino M, Monteleone P, Steardo L (1989) Repetitive growth hormone-releasing hormone administration restores the attenuated growth hormone (GH) response to GH-releasing hormone testing in normal aging. J Clin Endocrinol Metab 69:910–913.PubMedCrossRefGoogle Scholar
  24. Iranmanesh A, Lizarralde G, Veldhuis JD (1991) Age and relative adiposity are specific negative determinants of the frequency and amplitude of GH secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 73:1081–1088.PubMedCrossRefGoogle Scholar
  25. Kalk W, Vinik AI, Pimstone BL (1973) Growth hormone response to insulin hypoglycemia in the elderly. J Gerontol 28:431–433.PubMedGoogle Scholar
  26. Kelijman M, Frohman LA (1991) The role of the cholinergic pathway in growth hormone feedback. J Clin Endocrinol Metab 72:1081–1087.PubMedCrossRefGoogle Scholar
  27. Locatelli V, Torsello A, Redaelli M, Ghigo E, Massara F, Müller EE (1987) Cholinergic agonists and antagonists drugs modulate the growth hormone response to growth hormone releasing hormone in the rat: evidence for mediation by somatostatin. J Endocrinol 111:271–278.CrossRefGoogle Scholar
  28. Locatelli V, Cella SG, Cermenati P, Panzeri G, Sellan R, Muller EE (1989) Defective growth hormone (GH) secretion in aging mammals: contribution of central and peripheral inhibitory influences and of GH-releasing hormone. In: Valenti G (ed) Psychoneuroendocrinology of aging: basic and clinical aspects. Liviana, Padova, pp 61–71 (Fidia research series, vol 16)Google Scholar
  29. Massara F, Ghigo E, Demislis K, Tangolo D, Mazza E, Locatelli V, Müller EE, Molinatti GM, Camanni F (1986) Cholinergic involvement in the growth hormone releasing hormone-induced growth hormone release: studies in normal and acromegalic subjects. Neuro-endocrinology 43:670–675.Google Scholar
  30. Morimoto N, Kawakami F, Makino S, Chihara K, Hasegawa M, Shibata Y (1988) Age-related changes in growth hormone releasing factor and somatostatin and the rat hypothalamus. Neuroendocrinology 47:459–464.PubMedCrossRefGoogle Scholar
  31. Muggeo M, Fedele D, Tiengo A, Molinari M, Crepaldi G (1975) Human growth hormone and cortisol responses to insulin stimulation in aging. J Gerontol 30:546–550.PubMedGoogle Scholar
  32. Müller EE, Nisticò G (1989) Neurotransmitter regulation of the anterior pituitary. In: Müller EE, Nisticò G (eds) Brain messengers and the pituitary. Academic, San Diego, pp 404–537.Google Scholar
  33. Müller EE, Locatelli V, Ghigo E, Cella S, Loche S, Pintor G, Camanni F (1991) Involvement of brain catecholamines and acetylcholine in growth hormone deficiency states. Drugs 41:161–177.PubMedCrossRefGoogle Scholar
  34. Panzeri G, Torsello A, Cella SG, Muller EE, Locatelli V (1990) Age-related modulatory activity by a cholinergic agonist on the GH response to GHRH in the rat. PSEMB 193:301.Google Scholar
  35. Pavlov EP, Harman SM, Merriam GR, Gelato MC, Blackman MR (1986) Responses of growth hormone (GH) and somatomedin-C to GH-releasing hormone in healthy aging men. J Clin Endocrinol Metab 62:595–600.PubMedCrossRefGoogle Scholar
  36. Poehlman ET, Copeland KC (1990) Influence of physical activity on insulin-like growth factor-I in healthy younger and older men. J Clin Endocrinol Metab 71:1468–1473.PubMedCrossRefGoogle Scholar
  37. Raskind MA, Peskind ER, Verth RC, Wilkinson CW, Federighi D, Dorsa DM (1990) Differential effects of aging on neuroendocrine responses to physostigmine in normal men. J Clin Endocrinol Metab 70:1420–1427.PubMedCrossRefGoogle Scholar
  38. Richardson SB, Hollander CS, D’Eletto R (1980) Acetylcholine inhibits the release of somatostatin from rat hypothalamus in vitro. Endocrinology 107:1837–1842.CrossRefGoogle Scholar
  39. Robberecht P, Gillard M, Waelbroeck M, Camus JC, De Neef P, Christophe J (1986) Decreased stimulation of adenylate cyclase by growth hormone releasing factor in the anterior pituitary of old rats. Neuroendocrinology 44:429–432.PubMedCrossRefGoogle Scholar
  40. Ross RJM, Tsagarakis S, Grossman, A, Nhagafoong L, Touzel RJ, Rees LH, Besser GM (1987) GH feedback occurs through modulation of hypothalamic somatostatin under cholinergic control: studies with pyridostigmine and GHRH. Clin Endocrinol 27:727–733.CrossRefGoogle Scholar
  41. Rossor MN (1982) Dementia. Lancet II:1200–1204.CrossRefGoogle Scholar
  42. Rudman D (1985) Growth hormone, body composition and aging. J Am Geriatr Soc 33:800–807.PubMedGoogle Scholar
  43. Rudman D, Kutner MH, Rogers M, Lubin MF, Fleming GA, Bain RP (1981) Impaired growth hormone secretion in the adult population. J Clin Invest 67:1361–1369.PubMedCrossRefGoogle Scholar
  44. Rudman D, Feller AG, Nagraj HS (1990) Effects of human growth hormone in men over 60 years old. N Engl J Med 323:1–4.PubMedCrossRefGoogle Scholar
  45. Shibasaki T, Shizume K, Nakahara M, Masuda A, Jibiki K, Demura H, Wakabayashi I, Ling N (1984) Age-related changes in plasma growth hormone response to growth hormone-releasing factor in man. J Clin Endocrinol Metab 58:212–214.PubMedCrossRefGoogle Scholar
  46. Sonntag WE, Forman LJ, Miki N, Steger RW, Ramos Teresa, Arimura Akira, Meites J (1981) Effects of CNS active drugs and somatostatin antiserum on growth hormone release in young and old male rats. Neuroendocrinology 33:73–78.PubMedCrossRefGoogle Scholar
  47. Sonntag WE, Hylka VW, Meites J (1983) Impaired ability of old male rats to secrete growth hormone in vivo but not in vitro in response to hpGRF(1–44). Endocrinology 113:2305–2307.PubMedCrossRefGoogle Scholar
  48. Sonntag WE, Gottschall PE, Meites J (1986) Increased secretion of somatostatin-28 from hypothalamic neurons of aged rats in vitro. Brain Res 380:229–332.PubMedCrossRefGoogle Scholar
  49. Torsello A, Panzeri G, Cermenati P, Caroleo MC, Ghigo E, Camanni F, Müller EE, Locatelli V (1988) Involvement of the somatostatin and cholinergic systems in the mechanism of growth hormone autofeedback regulation in the rat. J Endocrinol 117:273–281.PubMedCrossRefGoogle Scholar
  50. Van Coevorden A, Mockel J, Laurent E (1991) Neuroendocrine rhythms and sleep in aging men. Am J Physiol 260:251–261.Google Scholar
  51. Vermeulen A (1987) Nyctohemeral growth hormone profiles in young and aged men: correlation with somatomedin-C levels. J Clin Endocrinol Metab 64:884–888.PubMedCrossRefGoogle Scholar
  52. Wehrenberg WB, Ling N (1983) The absence of an age-related change in the pituitary response to growth hormone-releasing factor in rats. Neuroendocrinology 37:463–466.PubMedCrossRefGoogle Scholar
  53. White P, Hiley CR, Goodhardt MJ (1977) Neocortical cholinergic neurons in elderly people. Lancet I:668–671.CrossRefGoogle Scholar
  54. Yu-Kai Sun YP, Fenoglio CM, Pushparaj N (1984) The effect of age on the number of pituitary cells immunoreactive to growth hormone and prolactin. Hum Pathol 15:169–180.CrossRefGoogle Scholar
  55. Zadik Z, Chalew SA, McCarter RJ, Meistas M, Kowarski AA (1985) The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 60:513–516.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • E. Ghigo
  • E. Arvat
  • S. Goffi
  • J. Bellone
  • M. Nicolosi
  • M. Procopio
  • M. Maccario
  • F. Camanni

There are no affiliations available

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