Journal of Clinical Endocrinology & Metabolism, Vol 81, 2111-2116, Copyright © 1996 by Endocrine Society

ARTICLES

Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone alkaline phosphatase isoenzyme

T Ono, S Kanzaki, Y Seino, DJ Baylink and S Mohan
Department of Pediatrics, Okayama University Medical School, Japan.

To investigate the contribution of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) to the regulation of bone growth in 10 GH-deficient Japanese children receiving recombinant GH therapy, we determined the percent increase from pretreatment levels of serum IGF-I, IGF-II, IGFBP-3, IGFBP-5, and bone-specific alkaline phosphatase isoenzyme (B-ALP). For 10 children between 6-13 yr of age, serum IGF-I and IGF-II were increased after 1 month of treatment by 53% and 7%, respectively; after 12 months of therapy, IGF levels remained elevated at 51% and 17%, respectively. Serum IGFBP-3 and IGFBP-5 were also increased after 1 month of GH therapy by 17% and 13% respectively; after 12 months of therapy, they remained elevated at 22% and 15%, respectively. After 12 months of treatment, the bone formation marker B- ALP was also elevated to 23% greater than pretreatment levels. The elevation of IGF-I induced by GH was significantly correlated with the increases in IGFBP-3 (r = 0.735; P < 0.0001) and IGFBP-5 (r = 0.795; P < 0.0001), and the elevation of B-ALP was also significantly positively correlated with the increases in IGF-I, IGF-II, IGFBP-3, and IGFBP-5 (r = 0.544, P < 0.0001; r = 0.268, P = 0.0399; r = 0.414, P = 0.0010; and r = 0.500, P < 0.0001, respectively). Our data are consistent with the anabolic effect on bone growth of GH treatment being mediated by IGF- II, IGFBP-3, and IGFBP-5 as well as by IGF-I. This is the first evidence that GH treatment increases IGF-II in GH-deficient children. This finding was probably the result of application of a valid assay that measures IGF-II without interference of IGFBPs.

This article has been cited by other articles:

				M. Malerba, S. Bossoni, A. Radaeli, E. Mori, S. Bonadonna, A. Giustina, and C. Tantucci Growth Hormone Response to Growth Hormone-Releasing Hormone Is Reduced in Adult Asthmatic Patients Receiving Long-term Inhaled Corticosteroid Treatment Chest, February 1, 2005; 127(2): 515 - 521. [Abstract] [Full Text] [PDF]

				S. Mohan, G. Masinde, X. Li, and D. J. Baylink Mapping Quantitative Trait Loci That Influence Serum Insulin-Like Growth Factor Binding Protein-5 Levels in F2 Mice (MRL/MpJ X SJL/J) Endocrinology, August 1, 2003; 144(8): 3491 - 3496. [Abstract] [Full Text] [PDF]

				T. Ueland, J. Bollerslev, A. Flyvbjerg, T. B. Hansen, N. Vahl, and L. Mosekilde Effects of 12 Months of GH Treatment on Cortical and Trabecular Bone Content of IGFs and OPG in Adults with Acquired GH Deficiency: A Double-Blind, Randomized, Placebo-Controlled Study J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2760 - 2763. [Abstract] [Full Text] [PDF]

				M. H. Aguiar-Oliveira, M. S. Gill, E. S. de, A. Barretto, M. R. S. Alcântara, F. Miraki-Moud, C. A. Menezes, A. H. O. Souza, C. E. Martinelli, F. A. Pereira, et al. Effect of Severe Growth Hormone (GH) Deficiency due to a Mutation in the GH-Releasing Hormone Receptor on Insulin-Like Growth Factors (IGFs), IGF-Binding Proteins, and Ternary Complex Formation Throughout Life J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4118 - 4126. [Abstract] [Full Text]

				H. Olivecrona, A. Hilding, C. Ekström, H. Barle, B. Nyberg, C. Möller, P. J. Delhanty, R. C. Baxter, B. Angelin, T. J. Ekström, et al. Acute and Short-Term Effects of Growth Hormone on Insulin-Like Growth Factors and Their Binding Proteins: Serum Levels and Hepatic Messenger Ribonucleic Acid Responses in Humans J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 553 - 560. [Abstract] [Full Text]

				D. R. Powell, S. K. Durham, E. D. Brewer, J. W. Frane, S. L. Watkins, R. J. Hogg, and S. Mohan Effects of Chronic Renal Failure and Growth Hormone on Serum Levels of Insulin-Like Growth Factor-Binding Protein-4 (IGFBP-4) and IGFBP-5 in Children: A Report of the Southwest Pediatric Nephrology Study Group J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 596 - 601. [Abstract] [Full Text]

				N. Kawai, S. Kanzaki, S. Takano-Watou, C. Tada, Y. Yamanaka, T. Miyata, M. Oka, and Y. Seino Serum Free Insulin-Like Growth Factor I (IGF-I), Total IGF-I, and IGF-Binding Protein-3 Concentrations in Normal Children and Children with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 82 - 89. [Abstract] [Full Text]

				T. Ueland, J. Bollerslev, T. B. Hansen, E. N. Ebbesen, L. Mosekilde, K. Brixen, A. Flyvbjerg, and O. Djøseland Increased Cortical Bone Content of Insulin-Like Growth Factors in Acromegalic Patients J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 123 - 127. [Abstract] [Full Text]

				N. S. Glaser, A. C. Shirali, D. M. Styne, and K. L. Jones Acid-base Homeostasis in Children With Growth Hormone Deficiency Pediatrics, December 1, 1998; 102(6): 1407 - 1414. [Abstract] [Full Text] [PDF]

				S. M. Twigg and R. C. Baxter Insulin-like Growth Factor (IGF)-binding Protein 5 Forms an Alternative Ternary Complex with IGFs and the Acid-labile Subunit J. Biol. Chem., March 13, 1998; 273(11): 6074 - 6079. [Abstract] [Full Text] [PDF]

				C. Ohlsson, B.-A. Bengtsson, O. G. P. Isaksson, T. T. Andreassen, and M. C. Slootweg Growth Hormone and Bone Endocr. Rev., February 1, 1998; 19(1): 55 - 79. [Abstract] [Full Text]

				G. L. Klein, S. E. Wolf, C. B. Langman, C. J. Rosen, S. Mohan, B. S. Keenan, S. Matin, C. Steffen, M. Nicolai, D. E. Sailer, et al. Effect of Therapy with Recombinant Human Growth Hormone on Insulin-Like Growth Factor System Components and Serum Levels of Biochemical Markers of Bone Formation in Children After Severe Burn Injury J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 21 - 24. [Abstract] [Full Text]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]