Advertisement

Direct Action of GH

  • O. G. P. Isaksson
  • J. Isgaard
  • A. Nilsson
  • A. Lindahl
Part of the Serono Symposia, USA book series (SERONOSYMP)

Abstract

Growth hormone (GH) has long been known to have a pivotal role in the regulation of somatic growth. Thus, GH deficiency results in proportionate dwarfism that is responsive to replacement therapy with GH. The physiological mechanism(s) by which GH exerts its stimulatory effect on somatic growth has not yet been elucidated. It has been demonstrated convincingly that administration of GH stimulates the growth of cartilage and other tissues by increasing the number of cells, showing that the effect of GH in vivo ultimately results in a stimulation of DNA synthesis and cell proliferation (1-3). However, efforts to demonstrate stimulatory effects of GH in vitro in explants of cartilage and other skeletal tissues have been unsuccessful in most cases.

Keywords

Growth Hormone Growth Plate Cloning Efficiency Proximal Zone Epiphyseal Growth Plate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Daughaday WH, Reeder C. Synchronous activation of DNA synthesis in hypophysectomized rat cartilage by growth hormone. J Lab Clin Med 1966; 68: 357–68.PubMedGoogle Scholar
  2. 2.
    Cheek DB. The effect of growth hormone on cell multiplication and cell size. In: Blizzard RM, ed. Human pituitary growth hormone: the 54th Ross conference on pediatric research. Columbus, Ohio: Ross Laboratories, 1966: 58–63.Google Scholar
  3. 3.
    Beach RK, Kostyo JL. Effect of growth hormone on the DNA content of muscles of young hypophysectomized rats. Endocrinology 1968; 92: 882–4.CrossRefGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    Daughaday WH, Hall K, Raben MS, Salmon WD Jr, Van Den Brande JL, Van Wyk JJ. Somatomedin: proposed designation for sulphation factor. Nature 1972; 235: 107.PubMedCrossRefGoogle Scholar
  6. 6.
    Hall K, Sara VR. Somatomedin levels in childhood, adolescence and adult life. Clin Endocrinol Metab 1984; 13: 91–112.PubMedCrossRefGoogle Scholar
  7. 7.
    Schoenle E, Zapf J, Humbel RE, Froesch ER. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 1982; 296: 252–3.PubMedCrossRefGoogle Scholar
  8. 8.
    Isaksson O, Jansson J-O, Gause IAM. Growth hormone stimulates longitudinal bone growth directly. Science 1982; 216: 1237–9.Google Scholar
  9. 9.
    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: 2563–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Isgaard J, Nilsson A, Lindahl A, Jansson J-O, Isaksson OGP. Effects of local administration of GH and IGF-I on longitudinal bone growth in rats. Am J Physiol 1986; 250 (Endocrinol Metab 13): E367–72.PubMedGoogle Scholar
  11. 11.
    Nilsson A, Isgaard J, Lindahl A, Dahlstrom A, Skottner A, Isaksson O. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science 1986; 233: 571–4PubMedCrossRefGoogle Scholar
  12. 12.
    Wroblewski J, Engstrom M, Skottner A, Madsen K, Friberg U. Subcel-lular location of IGF-I in chondrocytes from rat’ rib growth plate. Acta Endocrinol (Copenh) 1987; 115: 37–43.Google Scholar
  13. 13.
    D’Ercole AJ, Stiles AD, Underwood LE. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 1984; 81: 935–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Lund PK, Moats-Staats BM, Hynes MA, et al. Somatomedin-C/insulin- like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem 1986; 261: 14539–44.PubMedGoogle Scholar
  15. 15.
    Roberts CT Jr, Laky SR, Lowe WL, Seaman WT, LeRoith D. Molecular cloning of rat IGF-I cDNSs: differential mRNA processing and regulation by growth hormone in extrahepatic tissues. Mol Cell Endocrinol 1987 (in press).Google Scholar
  16. 16.
    Isgaard J, Nilsson A, Isaksson O, Moller C, Norsted G. Regulation of IGF-I mRNA in rat growth plate by growth hormone [Abstract]. Endocrine Society, 1987.Google Scholar
  17. 17.
    Morikawa M, Nixon T, Green H. Growth hormone and the adipose conver-sion of 3T3 cells. Cell 1982; 29: 783–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Green H, Morikawa M, Nixon T. A dual effector theory of growth hor-mone action. Differentiation 1985; 29: 195–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Zezulak KM, Green H. The generation of insulin-like growth factor-I sensitive cells by growth hormone action. Science 1986; 233: 551–3.PubMedCrossRefGoogle Scholar
  20. 20.
    Kember NF, Sissons HA. A quantitative histology of the human growth plate. J Bone Joint Surg 1976; 58B: 426–35.Google Scholar
  21. 21.
    Kember NF. Cell kinetics and the control of growth in long bones. Cell Tissue Kinet 1978; 11: 477–85.PubMedGoogle Scholar
  22. 22.
    Benya PD, Shaffer JD. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 1982; 30: 215–24.PubMedCrossRefGoogle Scholar
  23. 23.
    Lindahl A, Isgaard J, Nilsson A, Isaksson OGP. Growth hormone potentiates colony formation of epiphyseal chondrocytes in suspension culture. Endocrinology 1986; 118: 1843–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Lindahl A, Isgaard J, Carlsson L, Isaksson OGP. Differential effects of growth hormone and insulin like growth factor I (IGF-I) on colony formation of epiphyseal chondrocytes in suspension culture in rats of different ages. Endocrinology 1987 (in press).Google Scholar
  25. 25.
    D’Ercole AJ, Applewhite GT, Underwood LE. Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol 1980; 75: 315–28.PubMedCrossRefGoogle Scholar
  26. 26.
    Clemmons DR, Van Wyk JJ. Evidence for a functional role of endogenously produced somatomedin like peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells. J Clin Invest 1985; 75: 1914–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Schlechter NL, Russell SM, Spencer EM, Nicoll CS. Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin. Proc Natl Acad Sci USA 1986; 83: 7932–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Skottner A, Clark RG, Robinson ICAF, Fryklund L. Recombinant human insulin-like growth factor: testing the somatomedin hypothesis in hypophysectomized rats. J Endocrinol 1987; 112: 123–33.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • O. G. P. Isaksson
    • 1
  • J. Isgaard
    • 1
  • A. Nilsson
    • 1
  • A. Lindahl
    • 1
  1. 1.Department of PhysiologyUniversity of GoteborgGoteborgSweden

Personalised recommendations