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.

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.

[1]  S. Mohan,et al.  Evidence that human bone cells in culture secrete insulin‐like growth factor (IGF)‐II and IGF binding protein‐3 but not acid‐labile subunit both under basal and regulated conditions , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  R. Marcus,et al.  The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. , 1995, The Journal of clinical endocrinology and metabolism.

[3]  A. Sommer,et al.  Systemic administration of rhIGF-I or rhIGF-I/IGFBP-3 increases cortical bone and lean body mass in ovariectomized rats. , 1995, Bone.

[4]  R L Hintz,et al.  Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. , 1994, The Journal of clinical endocrinology and metabolism.

[5]  R. Marcus,et al.  Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. , 1994, The Journal of clinical endocrinology and metabolism.

[6]  E. Canalis,et al.  Complex pattern of insulin‐like growth factor binding protein expression in primary rat osteoblast enriched cultures: Regulation by prostaglandin E2, growth hormone, and the insulin‐like growth factors , 1994, Journal of cellular physiology.

[7]  J. Baker,et al.  Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r) , 1993, Cell.

[8]  C. Conover,et al.  Regulation and biological effect of endogenous insulin-like growth factor binding protein-5 in human osteoblastic cells. , 1993, The Journal of clinical endocrinology and metabolism.

[9]  D. Andress,et al.  Human osteoblast-derived insulin-like growth factor (IGF) binding protein-5 stimulates osteoblast mitogenesis and potentiates IGF action. , 1992, The Journal of biological chemistry.

[10]  B. Riggs,et al.  Basal and regulated secretion of insulin-like growth factor binding proteins in osteoblast-like cells is cell line specific. , 1992, The Journal of clinical endocrinology and metabolism.

[11]  S. Mohan,et al.  Isolation of a novel insulin-like growth factor (IGF) binding protein from human bone: a potential candidate for fixing IGF-II in human bone. , 1991, Biochemical and biophysical research communications.

[12]  M. Ranke,et al.  Short-term changes in serum insulin-like growth factors (IGF) and IGF binding protein 3 after different modes of intravenous growth hormone (GH) exposure in GH-deficient patients. , 1991, The Journal of clinical endocrinology and metabolism.

[13]  S. Mohan,et al.  Bone growth factors. , 1991, Clinical orthopaedics and related research.

[14]  H. Zeisel,et al.  A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. , 1990, The Journal of clinical endocrinology and metabolism.

[15]  S. Mohan,et al.  Primary structure of human skeletal growth factor: homology with human insulin-like growth factor-II. , 1988, Biochimica et biophysica acta.

[16]  E. Froesch,et al.  Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. , 1981, The Journal of clinical investigation.

[17]  C. Hanna,et al.  Changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3, growth hormone (GH)-binding protein, erythrocyte IGF-I receptors, and growth rate during GH treatment. , 1995, The Journal of clinical endocrinology and metabolism.

[18]  S. Mohan,et al.  Evidence that human bone cells in culture produce insulin-like growth factor-binding protein-4 and -5 proteases. , 1994, Endocrinology.

[19]  S. Mohan,et al.  Growth hormone stimulates cortical bone formation in immature hypophysectomized rats. , 1992, Endocrine research.

[20]  J. Clemens,et al.  Recombinant DNA-derived human insulin-like growth factor II (hIGF-II) stimulates growth in hypophysectomized rats. , 1989, Endocrine research.