The Role of the Somatotropic System in Cognition and Other Cerebral Functions

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) receptors can be found in several areas of the brain. GH receptors are mainly found in the choroid plexus, thalamus, hypothalamus, pituitary, putamen, and hippocampus, whereas IGF-1 receptors are mainly concentrated in the hippocampus and parahippocampal areas. In early life, GH and IGF-1 have an important role in the development and differentiation of the central nervous system. In the more developed central nervous system, GH and IGF-1 are thought to have a variety of functions such as a neuroprotective function, an appetite increasing function, various cognitive functions, and perhaps a blood flow-regulating function. In GH-deficient children and adults, improvement of cognitive functions was observed after the administration of GH. Furthermore, specific cognitive functions in healthy older subjects may improve after increasing GH or IGF-1 levels.

Growth hormone - insulin-like growth factor 1 - brain - cognitive functions

REFERENCES

• 1 Nyberg F, Burman P. Growth hormone and its receptors in the central nervous system-location and functional significance.  Horm Res. 1996;  45 18-22
• 2 Adem A, Jossan S S, d’Argy R. Insulin-like growth factor 1 (IGF-1) receptors in the human brain: quantitative autoradiographic localization.  Brain Res. 1989;  503 299-303
• 3 Coculescu M. Blood-brain barrier for human growth hormone and insulin-like growth factor-1.  J Pediatr Endocrinol Metab. 1999;  12 113-124
• 4 Han V K. Is the central nervous system a target for growth hormone and insulin-like growth factors?.  Acta Paediatr Suppl. 1995;  411 3-8
• 5 van Dam P S, Aleman A, de Vries W R et al.. Growth hormone, insulin-like growth factor I and cognitive function in adults.  Growth Horm IGF Res. 2000;  10 Suppl B S69-73
• 6 Johansson J O, Larsson G, Elmgren A et al.. Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and effects neurotransmitters.  Neuroendocrinology. 1995;  61 57-66
• 7 Hanci N, Kuday C, Oguzoglu S A. The effects of synthetic growth hormone on spinal cord injury.  J Neurosurg Sci. 1994;  38 43-49
• 8 Gorio A, Vergani L, Lesma E, Di Giulio A M. Neuroprotection, neurodegeneration, and interaction with insulin-like growth factor-1: novel non-anticoagulant action of glucosaminoglycans.  J Neurosci Res. 1998;  51 559-562
• 9 Winkler T, Sharma H S, Stalberg E, Badgaiyan R D, Westman J, Nyberg F. Growth hormone attenuates alterations in spinal cord evoked potentials and cell injury following trauma to the rat spinal cord. An experimental study using topical application of rat growth hormone.  Amino Acids. 2000;  19 363-371
• 10 Gustafson K, Hagberg H, Bengtsson B A, Brantsing C, Isgaard J. Possible protective role of growth hormone in hypoxia-ischaemia in neonatal rats.  Pediatr Res. 1999;  45 318-323
• 11 Schneider-Rivas S, Rivas-Arancibia S, Vazquez-Pereyra F, Vazquez-Sandoval R, Borgonio-Perez G. Modulation of long-term memory and extinction responses induced by growth hormone (GH) and growth hormone releasing hormone (GHRH) in rats.  Life Sci. 1995;  56 433-441
• 12 Nyberg F. Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance.  Front Neuroendocrinol. 2000;  21 330-348
• 13 Deijen J B, de Boer H, Blok G J, van der Veen E A. Cognitive impairments and mood disturbances in growth hormone deficient men.  Psychoneuroendocrinology. 1996;  21 313-322
• 14 Deijen J B, de Boer H, Blok G J, van der Veen E A. Cognitive changes during growth hormone replacement in adult men.  Psychoneuroendocrinology. 1998;  23 45-55
• 15 Lijffijt M, Van Dam P S, Kenemans J L et al.. Somatotropic-axis deficiency affects brain substrates of selective attention in childhood-onset growth hormone deficient patients.  Neurosci Lett. 2003;  353 123-126
• 16 Soares C N, Musolino N R, Cunha Neto M et al.. Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial.  Arq Neuropsiquiatr. 1999;  57 182-189
• 17 Baum H B, Katznelson L, Sherman J C. Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency.  J Clin Endocrinol Metab. 1998;  83 3184-3189
• 18 Obermayr R P, Mayerhofer L, Knechtelsdorfer M, Tragl K H, Geyer G. The reduced release of GH by GHRH in 8 subjects aged 65-69 years is augmented considerably by rivastigmine, a drug for Alzheimer's disease.  Gerontology. 2003;  49 191-195
• 19 Aleman A, Verhaar H J, de Haan E HF. Insulin-like growth factor I and cognitive functions in healthy older men.  J Clin Endocrinol Metab. 1999;  84 471-475
• 20 Vitiello M V, Merriam G R, Moe K E. IGF-I correlates with cognitive function in healthy older men and estrogenized women.  Gerontologist. 1999;  39 6
• 21 Vitiello M V, Baker L D, Mazzoni G. Growth hormone releasing hormone treatment improves cognitive function in healthy older men and women.  Gerontologist. 2003;  43 51-54
• 22 Murialdo G, Barreca A, Nobili F et al.. Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia.  J Endocrinol Invest. 2001;  24 139-146
• 23 Johansson P, Ray A, Lai Z, Zhai Q Z, Roos P, Nyberg F. Effects of intracerebroventricular injections of growth hormone on opioid peptides in the male rat.  Analgesia. 1995;  1 481-485
• 24 Bengtsson B Å, Edén S, Lönn L et al.. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.  J Clin Endocrinol Metab. 1993;  76 309-317
• 25 Burman P, Broman J E, Hetta J et al.. Quality of life in adults with growth hormone (GH) deficiency: response to treatment with recombinant human GH in a placebo-controlled 21 months trial.  J Clin Endocrinol Metab. 1995;  80 3585-3590
• 26 Gibney J, Wallace J D, Spinks T et al.. The effect of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients.  J Clin Endocrinol Metab. 1999;  84 2596-2602
• 27 Rosén T, Wirén L, Wilhelmsen L, Wiklund I, Bengtsson BÅ. Decreased psychological well-being in adult patients with growth hormone deficiency.  Clin Endocrinol (Oxf). 1994;  40 111-116
• 28 McGauley G A, Cuneo R C, Salomon F, Sonken P. Psychological well-being before and after growth hormone treatment in adults with growth hormone deficiency.  Horm Res. 1990;  33 52-54
• 29 Stabler B, Siegel P T, Clopper R R, Stoppani C E, Compton P G, Underwood L E. Behaviour change after growth hormone treatment of childeren with short stature.  J Pediatr. 1998;  133 366-373
• 30 Schneider H J, Pagotto U, Stalla G K. Central effects of the somatotropic system.  Eur J Endocrinol. 2003;  149 377-392
• 31 Stoving R K, Hangaard J, Hansen-Nord M, Hagen C. A review of endocrine changes in anorexia nervosa.  J Psychiatr Res. 1999;  33 139-152
• 32 Edén S, Engström B, Burman P, Holdstock C, Anders Karlsson F. Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients.  J Clin Endocrinol Metab. 2003;  88 5193-5198
• 33 Tassone F, Broglio F, Destefanis S et al.. Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity.  J Clin Endocrinol Metab. 2003;  88 5478-5483
• 34 Kalra S P, Kalra P S. Neuropeptide Y: a physiological orexigen modulated by the feedback action of ghrelin and leptin.  Endocrine. 2003;  22 49-56
• 35 Shaw T G, Mortel K F, Meyer J S, Rogers R L, Hardenberg J, Cutaia M M. Cerebral blood flow changes in benign aging and cerebrovascular disease.  Neurology. 1984;  34 855-862
• 36 Sonntag W E, Lynch C D, Cooney P T, Hutchins P M. Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1.  Endocrinology. 1997;  138 3515-3520