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The Mechanism of the Growth-Promoting Action of Growth Hormone

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Acromegaly

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Abstract

The mechanism of the growth-promoting action of growth hormone has been under investigation for many years. Freud et al. in 1939 found that in vivo administration of partially purified growth hormone preparations were able to increase the width of the tibial epiphysis (1). Ellis et al. in 1953 demonstrated that the stimulatory action of growth hormone was associated with an increase in the incorporation of sulfate into glyco-saminoglycans (2). Although unable to elicit a direct stimulatory effect of growth hormone on sulfate incorporation into cartilage in vitro, Salmon and Daughaday in their 1957 pioneering discovery showed that there resided in serum a growth hormone-dependent activity, designated “sulfation factor,” which possessed this property (3). They observed that the serum of hypophysectomized (hypox) rats contained very little sulfation activity, but serum from hypox rats treated with growth hormone contained increased amounts. Although the name sulfation factor was changed in 1972 to somatomedins, these observations were the birth of the somatomedin hypothesis: The growth-promoting effect of growth hormone is mediated by the somatomedins.

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References

  1. Freud J, Levie LH, Kroon DB. Observations on growth (chondrotrophic) hormone and localization of its point of attack. J Endocrinol 1939; 1:56–64.

    Article  CAS  Google Scholar 

  2. Ellis S, Huble J, Simpson ME. Influence of hypophysectomy and growth hormone on cartilage sulfate metabolism. Proc Soc Exp Biol Med 1953; 84:603.

    PubMed  CAS  Google Scholar 

  3. Salmon WD Jr, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 1957; 49:825–36.

    PubMed  CAS  Google Scholar 

  4. Holder AT, Preece MA, Spencer EM. Effect of bovine growth hormone and a partially pure preparation of somatomedin on various growth parameters in hypopituitary dwarf mice. J Endocrinol 1981; 89: 275–82.

    Article  PubMed  CAS  Google Scholar 

  5. Schoenle E, Zapf J, Humbel RE, Froesch ER. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 1982; 206:252–3.

    Article  Google Scholar 

  6. Schoenle E, Zapf J, Froesch ER. Long-term in vivo effects of insulin-like growth factors (IGF) I and II on growth indices: direct evidence in favor of the somatomedin hypothesis. In: Spencer EM, ed. Insulin-like growth factors-somatomedins. New York: Walter De Gruyter, 1983:51.

    Google Scholar 

  7. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 1978; 253:2769–76.

    PubMed  CAS  Google Scholar 

  8. Gospodarowicz D, Bialecki H, Greenburg G. Purification of the fibroblast growth factor activity from bovine brain. J Biol Chem 1978; 253:3736–43.

    PubMed  CAS  Google Scholar 

  9. Furlanetto RW, Underwood LE, Van Wyk JJ, D’Ercole AJ. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest 1977; 60:648–57.

    Article  PubMed  CAS  Google Scholar 

  10. Zapf J, Morell B, Walter H, Laron Z, Froesch ER. Serum levels of the insulin-like growth factor (IGF) and its carrier. Acta Endocrinol (Copenh) 1980; 95:507–17.

    Google Scholar 

  11. Spencer EM, Uthne E, Mims R. Somatomedin A levels measured by radioreceptor assay in acromegaly: relation to growth hormone levels. In: Giordano G, Van Wyk JJ, Minuto F, eds. Somatmedins and growth. London: Academic Press, 1979:335.

    Google Scholar 

  12. Underwood LE, D’Ercole AJ, Van Wyk JJ. Somatomedin-C and the assessment of growth. Pediatr Clin North Am 1980; 27:771.

    PubMed  CAS  Google Scholar 

  13. Copeland KC, Johnson DM, Kuehl TJ, Castracane VD. Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons. J Clin Endocrinol Metab 1984; 58:698–703.

    Article  PubMed  CAS  Google Scholar 

  14. Clemmons DR, Shaw DS. Variables controlling somatomedin production by cultured human fibroblasts. J Cell Physiol 1983; 115:137–43.

    Article  PubMed  CAS  Google Scholar 

  15. Enberg G, Carlquist M, Jornvall H, Hall K. The characterization of somatomedin A isolated by microcomputer controlled chromatography reveals an apparent identity to insulin-like growth factor I. Eur J Biochem 1984; 143:117–24.

    Article  PubMed  CAS  Google Scholar 

  16. Moses AC, Nissley SP, Short PA, et al. Increased levels of multiplication-stimulating activity, and insulin-like growth factor, in fetal rat serum. Proc Natl Acad Sci USA 1980; 77:3649–53.

    Article  PubMed  CAS  Google Scholar 

  17. Adams SO, Nissley SP, Greenstein LA, Yang YW-H, Rechler M. Synthesis of multiplication-stimulating activity (rat insulin-like growth factor II) by rat embryo fibroblasts. Endocrinology 1983; 112: 979–87.

    Article  PubMed  CAS  Google Scholar 

  18. Gavin JR III, Trivedi B. IGF-II receptor expression in developing tissues: models in vivo and in vitro. In: Spencer EM, ed. Insulin-like growth factors-somatomedins. New York: Walter De Gruyter, 1983:531.

    Google Scholar 

  19. Jansen M, van Schaik FMA, Ricker AT, et al. Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature 1983; 306.

    Google Scholar 

  20. Dull TJ, Gray A, Hayflick JS, Ullrich A. Insulin like growth factor II precursor gene organization in relation to insulin gene family. Nature 1984; 310.

    Google Scholar 

  21. Bell GI, Merryweather JP, Sanchez-Pescador R, et al. Sequence of a cDNA clone encoding human preproinsulin-like growth factor II. Nature 1984; 310.

    Google Scholar 

  22. Rotwein P. Two insulin-like growth factor I messenger RNAs are expressed in human liver. Proc Natl Acad Sci USA 1986; 83:77–81.

    Article  PubMed  CAS  Google Scholar 

  23. Tricoli JV, Rail LB, Scott J, Bell GI, Shows TB. Location of insulin-like growth factor genes to human chromosomes 11 and 12. Nature 1984; 310:784.

    Article  PubMed  CAS  Google Scholar 

  24. Hoppener JWM, Pagter-Holthuizen P, van Kessel AHMG, et al. The human gene encoding insulin-like growth factor I is located on chromosome 12. Hum Genet 1985; 69:157–60.

    Article  PubMed  CAS  Google Scholar 

  25. Pagter-Holthuizen P, Hoppener JWM, Jansen M, van Kessel AHMG, van Ommen GJB, Sussenbach JS. Chromosomal localization and preliminary characterization of the human gene encoding insulin-like growth factor II. Hum Genet 1985; 69:170–3.

    Article  PubMed  Google Scholar 

  26. Blundell TL, et al. Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding. Proc Natl Acad Sci USA 1978; 75:180.

    Article  PubMed  CAS  Google Scholar 

  27. Nissley SP, Short PA, Rechler MM, Podskalny JM, Coon HG. Proliferation of buffalo rat liver cells in serum-free medium does not depend upon multiplication stimulating activity (MSA). Cell 1977; 11:441.

    Article  PubMed  CAS  Google Scholar 

  28. Valliant SW, Peters M, Finley S, Fagin K. Insulin-like growth factors I(THR59): hypoglycemic potency and pharmacokinetics in conscious rats [Abstract]. The Endocrine Society 68th Annual Meeting 1986:392.

    Google Scholar 

  29. Guler HP, Zenobi P, Zapf J, et al. IGF I and II and recombinant human (RH) IGF I are hypoglycemic in the rat, mini-pig and men. The Endocrine Society 68th Annual Meeting 1986:394.

    Google Scholar 

  30. Kasuga M, Van Obberghen E, Nissley SP, Rechler MM. Demonstration of two subtypes of insulin-like growth factor receptors by affinity cross-linking. J Biol Chem 1981; 256:5305–8.

    PubMed  CAS  Google Scholar 

  31. Massague J, Czech MP. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem 1982; 257:5038–45.

    PubMed  CAS  Google Scholar 

  32. Stiles CD, Capone GT, Scher CD, Antoniades HN, Van Wyk JJ, Pledger WJ. Dual control of cell growth by somatomedins and platelet derived growth factor. Proc Natl Acad Sci USA 1979; 76:1279–83.

    Article  PubMed  CAS  Google Scholar 

  33. Clemmons DR, Van Wyk JJ, Pledger WJ. Sequential addition of platelet factor and plasma to BALB/c 3T3 fibroblast cultures stimulates somatomedin-C binding early in cell cycle. Proc Natl Acad Sci USA 1980; 77:6644.

    Article  PubMed  CAS  Google Scholar 

  34. Hintz RL, Liu F. Demonstration of specific plasma protein binding sites for somatomedin. J Clin Endocrinol Metab 1977; 45:988.

    Article  PubMed  CAS  Google Scholar 

  35. Zapf J, Waldvogel M, Froesch ER. Binding of nonsuppressible insulin-like activity to human serum: evidence for a carrier protein. Arch Biochem Biophys 1975; 168:638.

    Article  PubMed  CAS  Google Scholar 

  36. Meuli C, Zapf J, Froesch ER. NSILA-carrier protein abolishes the action of nonsuppressible insulin-like activity (NSILA-S) on perfused rat heart. Diabetologia 1978; 14:255.

    Article  PubMed  CAS  Google Scholar 

  37. Zapf J, Schoenle E, Jagars G, Sand I, Grunwald J, Froesch ER. Inhibition of the action of nonsuppressible insulin-like activity on isolated rat fat cells by binding to its carrier protein. J Clin Invest 1979; 63:1077.

    Article  PubMed  CAS  Google Scholar 

  38. Knauer DJ, Smith GL. Inhibition of biological activity of multiplication-stimulating activity by binding to its carrier protein. Proc Natl Acad Sci USA 1980; 77:7252–6.

    Article  PubMed  CAS  Google Scholar 

  39. Copeland KC, Johnson DM, Kuehl TJ, Castracane VD. Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons. J Clin Endocrinol Metab 1984; 58:698–703.

    Article  PubMed  CAS  Google Scholar 

  40. Furlanetto RW. The somatomedin-C binding protein: evidence for a heterologous subunit structure. J Clin Endocrinol Metab 1980; 51:12.

    Article  PubMed  CAS  Google Scholar 

  41. Hintz RL, Liu F, Rosenfeld RG, Kemp SF. Plasma somatomedin-binding proteins in hypopituitarism: changes during growth hormone therapy. J Clin Endocrinol Metab 1981; 53:100.

    Article  PubMed  CAS  Google Scholar 

  42. White RM, Nissley SP, Moses AC, Rechler MM, Johnsonbaugh RE. The growth hormone dependence of somatomedin-binding protein in human serum. J Clin Endocrinol Metab 1981; 53:49.

    Article  PubMed  CAS  Google Scholar 

  43. D’Ercole AJ, Willson DF, Underwood LE. Changes in the circulating form of serum somatomedin-C during fetal life. J Clin Endocrinol Metab 1980; 51:674.

    Article  PubMed  Google Scholar 

  44. Wilkins JR, D’Ercole AJ. Affinity-labeled plasma somatomedin-C/- insulin-like growth factor I binding proteins. J Clin Invest 1985; 75:1350–8.

    Article  PubMed  CAS  Google Scholar 

  45. Cochinov RH, Mariz IK, Hajek AS, Daughaday WH. Characterization of a protein in mid-term human amniotic fluid which reacts in the somato-medin-C radioreceptor assay. J Clin Endocrinol Metab 1977; 44:902.

    Article  Google Scholar 

  46. Drop SLS, Kortleve DJ, Guyda HJ. Isolation of a somatomedin-binding protein from preterm amniotic fluid. Development of a radioimmuno-assay. J Clin Endocrinol Metab 1984; 59:899.

    Article  PubMed  CAS  Google Scholar 

  47. Drop SLS, Kortleve DJ, Guyda HJ, Posner BI. Immunoassay of a somato-medin-binding protein from human amniotic fluid levels in fetal, neonatal, and adult sera. J Clin Endocrinol Metab 1984; 59:908.

    Article  PubMed  CAS  Google Scholar 

  48. Povoa G, Enberg G, Jornvall H, Kerstin H. Isolation and characterization of a somatomedin-binding protein from mid-term human amniotic fluid. Eur J Biochem 1984; 144:199–204.

    Article  PubMed  CAS  Google Scholar 

  49. Romanus JA, Terrell JE, Yang YW-H, Nissley SP, Rechler MM. Insulin-like growth factor carrier proteins in neonatal and adult rat serum are immunologically different: demonstration using a new radioim-munoassay for the carrier protein from BRL-3A rat liver cells. Endocrinology 1986; 118:1743–58.

    Article  PubMed  CAS  Google Scholar 

  50. Martin JL, Baxter RC. Antibody against acid-stable insulin-like growth factor binding protein detects 150,000 mol wt growth hormone-dependent complex in human plasma. J Clin Endocrinol Metab 1985; 61:799.

    Article  PubMed  CAS  Google Scholar 

  51. Spencer EM, The use of cultured rat hepatocytes to study the synthesis of somatomedin and its binding proteins. FEBS Lett 1979; 99:157.

    Article  PubMed  CAS  Google Scholar 

  52. D’Ercole AJ, Applewhite GT, Underwood LE. Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol 1980; 75:315.

    Article  PubMed  Google Scholar 

  53. Bennington J, Spencer EM, Reber K. Immunoperoxidase localization of insulin-like growth factor-I containing tissues. In: Spencer EM, ed. Insulin-like growth factors-somatomedins. New York: Walter De Gruyter, 1983:563–70.

    Google Scholar 

  54. Lund PK, Hynes MA, Moats-Staats B, D’Ercole AJ, Jansen M, Van Wyk JJ. Somatomedin/insulin-like growth factor mRNAs in rat fetal, neonatal and adult tissues. The Endocrine Society 68th Annual Meeting 1986;251.

    Google Scholar 

  55. Perkins SN, Zangger I, Eberwine JH, et al. Tissue distribution of insulin-like growth factor I and insulin-like growth factor II messenger RNA. The Endocrine Society 68th Annual Meeting 1986;252.

    Google Scholar 

  56. Van Wyk JJ, Moats-Staats BM, Jansen M, Lund PK. Rat brain IFG-II mRNAs after hypophysectomy and growth hormone replacement. The Endocrine Society 68th Annual Meeting 1986;253.

    Google Scholar 

  57. Clemmons DR, Elgin RG, Han VKM, Casella SJ, D’Ercole AJ, Van Wyk JJ. Cultured fibroblast monolayers secrete a protein that alters the cellular binding of somatomedin-C/insulin-like growth factor I. J Clin Invest 1986; 77:1548–56.

    Article  PubMed  CAS  Google Scholar 

  58. Isaksson OGP, Jansson J-0, Gause IAM. Growth hormone stimulates longitudinal growth directly. Science 1982; 216:1237–9.

    Article  PubMed  CAS  Google Scholar 

  59. Russell SM, Spencer EM. Local injections of human or rat growth hormone or of purified human somatomedin-C stimulate unilateral tibial epiphyseal growth in hypophysectomized rats. Endocrinology 1985; 116:2583–7.

    Article  Google Scholar 

  60. Schlechter NL, Russell SM, Greenberg S, Spencer EM, Nicoll CS. A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion. Am J Physiol 1986; 250:231–5.

    Google Scholar 

  61. Schlechter NL, Russell SM, Spencer EM, Nicoll CS. Evidence that the direct growth-promoting effects of growth hormone on cartilage in vivo are mediated by local production of somatomedin. Proc Natl Acad Sci USA 1986; 83(20):7932–4.

    Article  PubMed  CAS  Google Scholar 

  62. Spencer EM, Ross M, Smith B. The identity of human insulin-like growth factors I and II with somatomedins C and A: homology with rat IGF I and II. In: Spencer EM, ed. Insulin-like growth factors-somatomedins. New York: Walter De Gruyter, 1983:563–70.

    Google Scholar 

  63. Jansen M, van Schaik FMA, van Tol H, van den Brande JL, Sussenbach JS. Nucleotide sequences of cDNAs encoding precursors of human insulin-like growth factor II (IGF-II) and an IGF-II variant. FEBS Lett 1985; 179:243–6.

    Article  PubMed  CAS  Google Scholar 

  64. Zapf J, Walter H, Froesch ER. Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest 1981; 68:1321–30.

    Article  PubMed  CAS  Google Scholar 

  65. Whitefield HJ, Bruni CB, Frunzio R, Terrell JE, Nissley SP, Recher MM. Isolation of a cDNA clone encoding rat insulin-like growth factor-II precursor. Nature 1984; 312:277.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Children’s Hospital and University of California, San Francisco, CA, USA

    E. Martin Spencer

  2. Department of Physiology/Anatomy, University of California, Berkeley, CA, USA

    Nicole Schlechter, Sharon Russell & Charles Nicoll

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  1. E. Martin Spencer
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  2. Nicole Schlechter
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Editors and Affiliations

  1. Yale University, New Haven, Connecticut, USA

    Richard J. Robbins M.D. (Co-Chairman) (Co-Chairman)

  2. Cedars Sinai Medical Center, UCLA School of Medical Science, Los Angeles, California, USA

    Shlomo Melmed M.D. (Co-Chairman) (Co-Chairman)

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© 1987 Plenum Press, New York

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Spencer, E.M., Schlechter, N., Russell, S., Nicoll, C. (1987). The Mechanism of the Growth-Promoting Action of Growth Hormone. In: Robbins, R.J., Melmed, S. (eds) Acromegaly. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1913-9_8

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  • DOI: https://doi.org/10.1007/978-1-4613-1913-9_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9064-3

  • Online ISBN: 978-1-4613-1913-9

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