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Growth hormone binding protein and free growth hormone in chronic renal failure

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Abstract

Chronic renal failure in children is associated with growth failure. While the pathogenesis of uremic growth failure is multifactorial, an abnormal growth hormone/insulin-like growth factor (GH-IGF) axis is an important contributory element. Patients with uremia exhibit insensivivity to the action of GH, as exemplified by high plasma GH levels, low IGF-I activity, and poor somatic growth. This insensitivity can be overcome by supraphysiological doses of exogenous GH. Plasma GH binding protein (GHBP, the circulating ectodomain of the GH receptor) levels are decreased in patients with renal failure, as are hepatic GH receptor levels in animal models. Since GHBP levels are thought to reflect GH receptor levels in tissues, it is likely that the uremic GH insensitivity in humans is mediated by a decreased number of GH receptors. Another implication of the low plasma GHBP is a disproportionate elevation of free plasma GH (the biologically active moiety) relative to total GH, lending additional support to the concept of GH insensitivity in uremia. GH kinetics are altered in renal failure because of: (1) inability to excrete GH and (2) changes in the bound fraction of GH in the circulation.

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References

  1. Mehls O, Blum WF, Schaefer F, Tönshoff B, Schärer K (1992) Growth failure in renal disease. Baillieres Clin Endocrinol Metab 6:665–685

    PubMed  Google Scholar 

  2. Tönshoff B, Schaefer F, Mehls O (1990) Disturbance of growth hormone — insulin-like growth factor axis in uraemia. Pediatr Nephrol 4:654–662

    PubMed  Google Scholar 

  3. Fine RN, Kohaut EC, Brown D et al (1994) Growth after recombinant human growth hormone treatment in children with chronic renal failure: report of a multicenter randomized double-blind placebo-controlled study. J Pediatr 124:374–382

    PubMed  Google Scholar 

  4. Blum WF, Ranke M, Kietzmann K, Tönshoff B, Mehls O (1991) Growth hormone resistance and inhibition of IGF activity by excess of IGF-binding proteins in uremia. Pediatr Nephrol 5:539–544

    PubMed  Google Scholar 

  5. Baumann G, Shaw MA, Amburn K (1994) Circulating growth hormone binding proteins. J Endocrinol Invest 17:67–81

    PubMed  Google Scholar 

  6. Baumann G (1994) Growth hormone binding protein: state of the art. J. Endocrinol 141:1–6

    PubMed  Google Scholar 

  7. Leung DW, Spencer SA, Cachianes G, et al (1987) Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature 330:537–543

    PubMed  Google Scholar 

  8. Baumann G, Shaw MA (1990) A second, lower affinity growth hormone-binding protein in human plasma. J Clin Endocrinol Metab 70:680–686

    PubMed  Google Scholar 

  9. Baumann G, Amburn K, Shaw M (1988) The circulating growth hormone-binding protein complex: a major constituent of plasma growth hormone in man. Endocrinology 122:976–984

    PubMed  Google Scholar 

  10. Finidori J, Postel-Vinay MC, Kleinknecht C (1980) Lactogenic and somatotropic binding sites in liver membranes of rats with renal insufficiency. Endocrinology 106:1960–1965

    PubMed  Google Scholar 

  11. Chan W, Valerie KC, Chan JCM (1993) Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake. Kidney Int 43:790–795

    PubMed  Google Scholar 

  12. Tönshoff B, Edén S, Weiser E, et al (1994) Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia. Kidney Int 45:1085–1092

    PubMed  Google Scholar 

  13. Baumann G, Amburn KD, Buchanan TA (1987) The effect of circulating growth hormone-binding protein on metabolic clearance, distribution and degradation of human growth hormone. J Clin Endocrinol Metab 64:657–660

    PubMed  Google Scholar 

  14. Veldhuis J, Johnson ML, Faunt LM, Mercado M, Baumann G (1993) Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. J Clin Invest 91:629–641

    PubMed  Google Scholar 

  15. Johnson V, Maack T (1977) Renal extraction, filtration, absorption, and catabolism of growth hormone. Am J Physiol 233:F185–196

    PubMed  Google Scholar 

  16. Haffner D, Schaefer F, Girard J, Ritz E, Mehls O (1994) Metabolic clearance of recombinant human growth hormone in health and chronic renal failure. J Clin Invest 93:1163–1171

    PubMed  Google Scholar 

  17. Bullier-Picard F, Postel-Vinay MC, Kayser C (1988) In-vivo uptake of human growth hormone in the male rat liver. J Endocrinol 121:19–25

    Google Scholar 

  18. Baumann G, Lowman HB, Mercado M, Wells JA (1994) The stoichiometry of growth hormone-binding protein complexes in human plasma: comparison with cell surface receptors. J Clin Endocrinol Metab 78:1113–1118

    PubMed  Google Scholar 

  19. Mannor DA, Winer LM, Shaw MA, Baumann G (1991) Plasma growth hormone binding proteins: effect on growth hormone binding to receptors and on growth hormone action. J Clin Endocrinol Metab 73:30–34

    PubMed  Google Scholar 

  20. Clark RG, Cunningham B, Moore JA, et al (1991) Growth hormone binding protein enhances the growth promoting activity of GH in the rat. Abstracts of the 73rd Meeting of the Endocrine Society, p. 433, The Endocrine Society, Bethesda, MD

    Google Scholar 

  21. Jan T, Shaw MA, Baumann G (1991) Effects of growth hormone-binding proteins on serum growth hormone measurements. J Clin Endocrinol Metab 72:387–391

    PubMed  Google Scholar 

  22. Veldhuis JD, Iranmesh A, Wilkowski MJ, Samojlik E (1994) Neuroendocrine alterations in the somatotropic and lactotropic axes in uremic men. Eur J Endocrinol 131:489–498

    PubMed  Google Scholar 

  23. Tönshoff B, Veldhuis JD, Heinrich U, Mehls O (1995) Deconvolution analysis of spontaneous growth hormone secretion in prepubertal children with preterminal chronic renal failure and with end-stage renal disease. Pediatr Res 37:86–93

    PubMed  Google Scholar 

  24. Schaefer F, Veldhuis JD, Stanhope R, Jones J, Schärer K, et al (1994) Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. J Clin Endocrinol Metab 78:1298–1306

    PubMed  Google Scholar 

  25. Baumann G, Shaw MA, Amburn K (1989) Regulation of plasma growth hormone-binding proteins in health and disease. Metabolism 38:683–689

    PubMed  Google Scholar 

  26. Postel-Vinay MC, Tar A, Crosnier H, Broyer M, Rappaport R, Tönshoff B, Mehls O (1991) Plasma growth hormone-binding activity is low in uraemic children. Pediatr Nephrol 5:545–547

    PubMed  Google Scholar 

  27. Maheshwari HG, Rifkin I, Butler J, Norman M (1992) Growth hormone binding protein in patients with renal failure. Acta Endocrinol (Copenh) 127:485–488

    Google Scholar 

  28. Kratzsch J, Blum WF, Seliusko T, Keller E (1993) Radioimmunologic determination of GHBP in sera of children with short stature. Pediatr Res 33 [Suppl]:S48

    PubMed  Google Scholar 

  29. Schaefer F, Baumann G, Haffner D, et al (1996) Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady-state concentrations of GH in plasma. J Clin Endocrinol Metab 81:22–31

    PubMed  Google Scholar 

  30. Haldosen LA, Gustafsson JA (1990) Detection of glycoslated growth hormone-binding proteins in rat serum. Mol cell Endocrinol 68:187–194

    PubMed  Google Scholar 

  31. Smith WC, Talamantes F (1988) Gestational profile and affinity cross-linking of the mouse serum growth hormone-binding protein. Endocrinology 123:1489–1494

    PubMed  Google Scholar 

  32. Baumann G (1989) Circulating binding proteins for human growth hormone. In: Müller EE, Cocchi D, Locatelli V (eds) Advances in growth hormone and growth factor research. Springer, Berlin Heidelberg New York, pp 69–83

    Google Scholar 

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  1. Center for Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Medical School, 303 East Chicago Avenue, 60611, Chicago, IL, USA

    Gerhard Baumann

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  1. Gerhard Baumann
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Baumann, G. Growth hormone binding protein and free growth hormone in chronic renal failure. Pediatr Nephrol 10, 328–330 (1996). https://doi.org/10.1007/BF00866772

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  • DOI: https://doi.org/10.1007/BF00866772

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