Abstract
To clarify the influence of nutrition on the GH-IGF axis in protein-energy malnutrition (PEM), we determined the serum levels of GH, GH-binding proteins(BP) (GHBPs), IGF-I, and IGFBPs in nine children with kwashiorkor and 13 with marasmus, before and after nutritional rehabilitation. In a basal condition, the GH level was significantly higher in the two malnourished groups than in controls (p < 0.01); in contrast, the second fraction of GHBP was lower and seemed to be related to the high GH and to a reduction in GH receptors. After refeeding, the GH level increased and the second fraction of GHBP decreased. The IGF-I basal level was higher in kwashiorkor than in marasmus subjects (p < 0.05), but in both groups it was significantly lower than in controls (p < 0.01); after refeeding it increased. IGFBP-3, measured by RIA and Western blotting techniques, was in the control range in the kwashiorkor group but in the marasmic group it was significantly lower than in controls; after refeeding it decreased in kwashiorkor (p < 0.01 versus basal values) and increased in marasmus (p < 0.05 versus prerefeeding level). When sera of malnourished patients were mixed with adult control sera, incubated for 5 h at 37°C, and assessed by ligand blotting, a low IGFBP-3 level in marasmus was found to be due to increased adaptive proteolysis of IGFBP-3; in contrast, in kwashiorkor the IGFBP-3 proteolytic activity was very low, probably because of inhibition by aflatoxins. These findings confirm that malnutrition affects the GH-IGF axis.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BP:
-
binding protein
- PEM:
-
protein-energy malnutrition
- AU:
-
absorption unit
References
Thissen JP, Ketelslegers JM, Underwood LE 1994 Nutritional regulation of the insulin-like growth factors. Endocr Rev 15: 80–101.
Grant DB, Hambley JB, Becker D, Pimstone BL 1975 Reduced sulphation factor in undernourished children. Arch Dis Child 48: 596–600.
Hintz RL, Suskind R, Amatayakul K, Thanangkul O, Olson R 1978 Plasma somatomedin and growth hormone values in children with protein-calorie malnutrition. J Pediatr 92: 153–156.
Baumann G 1994 Growth hormone-binding proteins: state of the art. Endocrinology 141: 1–6.
Jones JI, Clemmons DR 1995 Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16: 34
Wellcome Trust Working Party 1970 Classification of infantile malnutrition. Lancet 2: 302–303.
Tar A, Hocquette J-F, Souberbielle J-C, Clot J-P, Brauner R, Postel- Vinay M-C 1990 Evaluation of the growth hormone-binding proteins in human plasma using high pressure liquid chromatography gel filtration. J Clin Endocrinol Metab 71: 1202–1207.
Hardouin S, Hossenlopp P, Segovia B, Seurin D, Portolan G, Lassarre C, Binoux M 1987 Heterogeneity of insulin-like growth factor binding proteins and relationships between structure and affinity. I. Circulating forms in man. Eur J Biochem 170: 121–132.
Davenport ML, Isley WL, Pucilowska JB, Pemberton LB, Lyman B, Underwood LE, Clemmons DR 1992 Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery. J Clin Endocrinol Metab 75: 590–595.
Sempé M, Pédron G, Roy-Pernot M-P 1979 Auxologie, méthode et séquences. Laboratoire Thérapic, Paris
Soliman AT, Hassan AEHI, Aref MK, Hintz RL, Rosenfeld RG, Rogol AD 1986 Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. Pediatr Res 20: 1122–1130.
Smith IF, Latham MC, Azubuike JA, Butler WR, Phillips LS, Pond WG, Enwonwu CO 1981 Blood plasma levels of cortisol, insulin, growth hormone and somatomedin in children with marasmus, kwashiorkor, and intermediate forms of protein energy malnutrition. Proc Soc Exp Biol Med 167: 607–611.
Hochberg Z, Hertz P, Colin V, Ish-Shalom S, Yeshurun D, Youdim MBH, Amit T 1992 The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. Metabolism 41: 106–112.
Murata A, Yasuda T, Niimi H 1992 Growth hormone-binding protein in patients with anorexia nervosa determined in two assay systems. Horm Metab Res 24: 297–299.
Ross R, Miell J, Freeman E, Jones J, Matthews D, Preece M, Buchanan C 1991 Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. Clin Endocrinol 35: 47–54.
Underwood LE, Clemmons DR, Maes M, D'Ercole J, Ketelslegers J-M 1986 Regulations of somatomedin-C/insulin-like growth factor I by nutrients. Horm Res 24: 166–176.
Dauncey MJ, Shakespear RA, Rudd BT, Ingram DL 1990 Variations in somatomedin-C/insulin-like growth factor-I associated with environmental temperature and nutrition. Horm Metab Res 22: 261–264.
Baumann G, Shaw MA, Amburn K 1989 Regulation of plasma growth hormone-binding proteins in health and disease. Metabolism 38: 683–689.
Daughaday WH, Trivedi B 1991 Clinical aspects of GH binding proteins. Acta Endocrinol 124 ( suppl 2): 27–32.
Underwood LE, Thissen J-P, Lemozy S, Ketelslegers J-M, Clemmons DR 1994 Hormonal and nutritional regulation of IGF-I, its binding proteins. Horm Res 42: 145–151.
Gargosky SE, Pham HM, Wilson KF, Liu F, Giudice LC, Rosenfeld RG 1992 Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting. Endocrinology 131: 3051–3060.
Muller HL, Oh Y, Gargosky SE, Wilson KF, Lehrnbecher T, Rosenfeld RG 1994 Insulin-like growth factor binding protein-3 concentrations and insulin-like growth factor binding protein-3 protease activity in sera of patients with malignant solid tumors or leukemia. Pediatr Res 35: 720–724.
Lassarre C, Lalou C, Perin L, Binoux M 1994 Protease-induced alteration of insulin-like growth factor binding protein-3 as detected by radioimmunoassay. Agreement with ligand blotting data. Growth Regul 4: 48–55.
Dauncey MJ, Rudd BT, White DA, Shakespear RA 1993 Regulation of insulin-like growth factor binding proteins in young growing animals by alteration of energy status. Growth Regul 3: 198–207.
Pucilowska JB, Davenport ML, Kabir I, Clemmons DR, Thissen J-P, Butler T, Underwood LE 1993 The effect of dietary protein supplementation on insulin-like growth factors (IGFs) and IGF-binding proteins in children with shigellosis. J Clin Endocrinol Metab 77: 1516–1521.
Blat C, Villaudy J, Binoux M 1994 In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells. J Clin Invest 93: 2286–2290.
Hendrickse RG 1991 Kwashiorkor: the hypothesis that incriminates aflatoxins. Pediatrics 88: 376–379.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zamboni, G., Dufillot, D., Antoniazzi, F. et al. Growth Hormone-Binding Proteins and Insulin-Like Growth Factor-Binding Proteins in Protein-Energy Malnutrition, before and after Nutritional Rehabilitation. Pediatr Res 39, 410–414 (1996). https://doi.org/10.1203/00006450-199603000-00006
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199603000-00006
This article is cited by
-
Exogenous recombinant human growth hormone effects during suboptimal energy and zinc intake
Nutrition & Metabolism (2005)
