Hormonal Feedback Regulation of Brain IGF-I and IGF-II Gene Expression

  • Teresa L. Wood
  • Michael Berelowitz
  • Jeffrey F. McKelvy


Release of anterior pituitary hormones is mediated by peptides produced by secretory neurons in the hypothalamus or preoptic area. The releasing or inhibiting factors are stored in nerve endings that lie in the median eminence and are secreted as the result of electrical activity. The hypothalamic peptides then travel through the portal system to the anterior pituitary where they interact with specific surface receptors to trigger release of pituitary trophic hormones. These, in turn, regulate physiologic processes elsewhere in the body either directly or indirectly through release of target gland hormones.


Growth Hormone Choroid Plexus Messenger Ribonucleic Acid Pituitary Growth Hormone Growth Hormone Release Factor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    W. H. Daughaday, K. Hall, M. S. Raben, W. D. Salmon, Jr., J. L. van der Brande, and J. J. van Wyk, Somatomedin: Proposed designation for sulphation factor, Nature 235:107 (1972).PubMedCrossRefGoogle Scholar
  2. 2.
    E. Schoenle, J. Zapf, R. E. Humbel, and E. R. Froesch, Insulin-like growth factor I stimulates growth in hypophysectomized rats, Nature 296:252 (1982).PubMedCrossRefGoogle Scholar
  3. 3.
    C. D. Scott, J. L. Martin, and R. C. Baxter, Rat hepatocyte insulin-like growth factor-I and binding protein: Effect of growth hormone in vitro and in vivo, Endocrinology 116:1102 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    D. R. Clemmons, J. J. van Wyk, E. C. Ridgway, B. Kliman, R. N. Kjellberg, and L.E. Underwood, Evaluation of acromegaly by radioimmunoassay of somatomedin-C, New Engl. J. Med. 301:1138 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    R. C. Baxter, The somatomedins: Insulin-like growth factors, Adv. Clin. Chem. 25:49 (1986).PubMedCrossRefGoogle Scholar
  6. 6.
    G. Oppizzi, M. M. Petroncini, D. Dallabonzana, R. Cozzi, G. Verde, P. G. Chiodini, and A. Liuzzi, Relationship between somatomedin-C and growth hormone levels in acromegaly: Basal and dynamic evaluation, J. Clin. Endocrin. Metab. 63:1348 (1986).CrossRefGoogle Scholar
  7. 7.
    J. C. Schwander, C. Hauri, J. Zapf, and E. R. Froesch, Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: Dependence on growth hormone status, Endocrinology 113:297 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    L. J. Murphy, G. I. Bell, and H. G. Friesen, Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat, Endocrinology 120:1279 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    L. J. Murphy, G. I. Bell, M. L. Duckworth, and H. G. Friesen, Identification, characterization, and regulation of a rat complementary deoxyribonucleic acid which encodes insulin-like growth factor-I, Endocrinology 121:684 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    C. T. Roberts, Jr., S. R. Lasky, W. L. Lowe, Jr., W. T. Seaman, and D. LeRoith, Molecular cloning of rat insulin-like growth factor I complementary deoxyribonucleic acids: differential messenger ribonucleic acid processing and regulation by growth hormone in extrahepatic tissues, Mol. Endocrinol. 1:243 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    A. J. D’Ercole, A. D. Stiles, and L. E. Underwood, Tissue concentrations of somatomedin C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action, Proc. Natl. Acad. Sci. USA 81:935 (1984).PubMedCrossRefGoogle Scholar
  12. 12.
    C. C. Orlowski and S. D. Chernausek, Discordance of serum and tissue somatomedin levels in growth hormone-stimulated growth in the rat, Endocrinology 123:44 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    M. A. Hynes, J. J. van Wyk, P. J. Brooks, A. J. D’ercole, M. Jansen, and P. K. Lund, Growth hormone dependence of somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II messenger ribonucleic acids, Mol. Endocrinol. 1:233 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    J. Zapf, H. Walters, and E. R. Froesch, Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extra-pancreatic tumor hypoglycemia, J. Clin. Invest. 68:1321 (1981)PubMedCrossRefGoogle Scholar
  15. 15.
    S. O. Adams, S. P. Nissley, M. Kasuga, T. P. Foley, and M. M. Rechler, Receptors for insulin-like growth factors and growth effects of multiplication-stimulating activity (rat IGF-II) in rat embryo fibroblasts, Endocrinology 112:971 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    H. D. Mosier, Jr., E. M. Spencer, L. C. Dearden, and R. A. Jansons, The effect of glucocorticoids on plasma insulin-like growth factor I concentration in the rat fetus, Pediatr. Res. 22:92 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    K. Pavelic, D. Vrbanec, S. Marusic, S. Levanat, and T. Cabrijan, Autocrine tumor growth regulation by somatomedin C: An in vitro model, J. Endocrinol. 109:233(1986).PubMedCrossRefGoogle Scholar
  18. 18.
    M. Adamo, H. Werner, W. Farnsworth, C. T. Roberts, Jr., M. Raizada, and D. LeRoith, Dexamethasone reduces steady state insulin-like growth factor I messenger ribonucleic acid levels in rat neuronal and glial cells in primary culture, Endocrinology 123:2565 (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    H. Katakami, T. R. Downs, and L. A. Frohman, Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism, J. Clin. Invest. 77:1704 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    R. Valcavi, C. Dieguez, M. Preece, A. Taylor, I. Portioli, and M. F. Scanlon, Effect of thyroxine replacement therapy on plasma insulin-like growth factor 1 levels and growth hormone responses to growth hormone releasing factor in hypothyroid patients, Clin. Endocrinol. 27:85 (1987).CrossRefGoogle Scholar
  21. 21.
    M. Binoux, A. Faivre-Bauman, C. Lassarre, A. Barret, and A. Tixier-Vidal, Triiodothyronine stimulates the production of insulin-like growth factor (IGF) by fetal hypothalamus cells cultured in serum-free medium, Dev. Brain Res. 21:319 (1985).CrossRefGoogle Scholar
  22. 22.
    C.-J. Hsu and J. M. Hammond, Gonadotropins and estradiol stimulate immunoreactive insulin-like growth factor-I production by porcine granulosa cells in vitro, Endocrinology 120:198 (1987).PubMedCrossRefGoogle Scholar
  23. 23.
    V. K. M. Han, J. M. Lauder, and A. J. D’Ercole, Characterization of somatomedin/insulin-like growth factor receptors and correlation with biologic action in cultured neonatal rat astroglial cells, J. Neurosci. 7:501 (1987).PubMedGoogle Scholar
  24. 24.
    N. J. Bohannon, E. S. Corp, B. J. Wilcox, D. P. Figlewicz, D. M. Dorsa, and D. G. Baskin, Localization of binding sites for insulin-like growth factor-I (IGF-I) in the rat brain by quantitative autoradiography, Brain Res. 444:205 (1988).PubMedCrossRefGoogle Scholar
  25. 25.
    M. Smith, J. Clemens, G. A. Kerchner, and L. G. Mendelsohn, The insulin-like growth factor-II (IGF-II) receptor of rat brain: regional distribution visualized by autoradiography, Brain Res. 445:241 (1988).PubMedCrossRefGoogle Scholar
  26. 26.
    H. Abe, M. E. Molitch, J. J. van Wyk, and L. E. Underwood, Human growth hormone and somatomedin C suppress the spontaneous release of growth hormone in unanesthetized rats, Endocrinology 113:1319 (1983).PubMedCrossRefGoogle Scholar
  27. 27.
    G. S. Tannenbaum, H. J. Guyda, and B. I. Posner, Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain, Science 220:77 (1983).PubMedCrossRefGoogle Scholar
  28. 28.
    M. Berelowitz, S. L. Firestone, and L. A. Frohman, Effects of growth hormone excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution, Endocrinology 109:714 (1981).PubMedCrossRefGoogle Scholar
  29. 29.
    S. Yamashita and S. Melmed, Insulin-like growth factor I action on rat anterior pituitary cells: Suppression of growth hormone secretion and messenger ribonucleic acid levels, Endocrinology 118:176 (1986).PubMedCrossRefGoogle Scholar
  30. 30.
    G. P. Ceda, R. G. Davis, R. G. Rosenfeld, and A. R. Hoffman, The growth hormone (GH)-releasing hormone (GHRH)-GH-somatomedin axis: Evidence for rapid inhibition of GHRH-elicited GH release by insulin-like growth factors I and II, Endocrinology 120:1658 (1987).PubMedCrossRefGoogle Scholar
  31. 31.
    T. Noguchi, L. M. Kurata, and T. Sugisaki, Presence of a somatomedin-C-immunoreactive substance in the central nervous system: Immunohistochemical mapping studies, Neuroendocrinology 46:277 (1987).PubMedCrossRefGoogle Scholar
  32. 32.
    G. K. Haselbacher, M. E. Schwab, A. Pasi, and R. E. Humbel, Insulin-like growth factor II (IGF II) in human brain: Regional distribution of IGF II and of higher molecular mass forms, Proc. Natl. Acad. Sci. USA 82:2153 (1985).PubMedCrossRefGoogle Scholar
  33. 33.
    P. Rotwein, S. K. Bergess, J. D. Milbrandt, and J. E. Krause, Differential expression of insulin-like growth factor genes in rat central nervous system, Proc. Natl. Acad. Sci. USA 85:265 (1988).PubMedCrossRefGoogle Scholar
  34. 34.
    F. Stylianopoulou, J. Herbert, M. B. Soares, and A. Efstratiadis, Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system, Proc. Natl. Acad. Sci. USA 85:141 (1988).PubMedCrossRefGoogle Scholar
  35. 35.
    M. A. Hynes, P. J. Brooks, J. J. van Wyk, and P. K. Lund, Insulin-like growth factor II messenger ribonucleic acids are synthesized in the choroid plexus of the rat brain, Mol. Endocrinol. 2:47 (1988).PubMedCrossRefGoogle Scholar
  36. 36.
    R. Ballotti, F. C. Nielson, N. Pringfe, A. Kowalski, W. D. Richardson, E. van Obberghen, and S. Gammeltoft, IGF-I in cultured rat astrocytes, expression of the gene and receptor tyrosine kinase, EMBO J. 6:3633 (1987).PubMedGoogle Scholar
  37. 37.
    L. S. Mathews, G. Norstedt, and R. D. Palmiter, Regulation of insulin-like growth factor I gene expression by growth hormone, Proc. Natl. Acad. Sci. USA 83:9343 (1986).PubMedCrossRefGoogle Scholar
  38. 38.
    M. Blum, Regulation of neuroendocrine peptide gene expression, Meth. Enzymol. 168:3 (1988).Google Scholar
  39. 39.
    W. L. Lowe, Jr., C. T. Roberts, Jr., S. R. Lasky, and D. LeRoith, Differential expression of alternative 5′ untranslated regions in mRNAs encoding rat insulin-like growth factor I, Proc. Natl. Acad. Sci. USA 84:8946 (1987).PubMedCrossRefGoogle Scholar
  40. 40.
    W. L. Lowe, Jr., S. R. Lasky, D. LeRoith, and C. T. Roberts, Jr., Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E-peptides: Evidence for differential processing and regulation in liver, Mol. Endocrinol. 2: 528 (1988).PubMedCrossRefGoogle Scholar
  41. 41.
    E. C. Hoyt, J. J. van Wyk, and P. K. Lund, Tissue and development specific regulation of a complex family of rat insulin-like growth factor I messenger ribonucleic acids, Mol. Endocrinol. 2:1077 (1988).PubMedCrossRefGoogle Scholar
  42. 42.
    M. B. Soares, A. Turken, D. Ishii, L. Mills, L. V. Episkopou, S. Cotter, S. Zeitlin and A. Efstratiadis, Rat insulin-like growth factor II gene, J. Moi. Biol. 192, 737 (1986).CrossRefGoogle Scholar
  43. 43.
    A. Gray, A. W. Tarn, T. J. Dull, J. Hayflick, J. Pintar, W. K. Cavenee, A. Koufos, and A. Ullrich, Tissue-specific and developmentally regulated transcription of the insulin-like growth factor 2 gene, DNA 6:283 (1987).PubMedCrossRefGoogle Scholar
  44. 44.
    J.-C. Irminger, K. M. Rosen, R. E. Humbel, and L. Villa-Komaroff, Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5’ untranslated regions, Proc. Natl. Acad. Sci. USA 84:6330 (1987).PubMedCrossRefGoogle Scholar
  45. 45.
    P. N. Schofield and V. E. Tate, Regulation of human IGF-II transcription in fetal and adult tissues, Development 101:793 (1987).PubMedGoogle Scholar
  46. 46.
    L. Chiariotti, A. L. Brown, R. Frunzio, D. R. Clemmons, M. M. Rechler, and C. B. Bruni, Structure of the rat insulin-like growth factor II transcriptional unit: Heterogeneous transcripts are generated from two promoters by use of multiple polyadenylation sites and differential ribonucleic acid splicing, Mol. Endocrinol. 2:1115 (1988).PubMedCrossRefGoogle Scholar
  47. 47.
    F. A. McMorris, T. M. Smith, S. DeSalvo, and R. W. Furlanetto, Insulin-like growth factor I/somatomedin C: A potent inducer of oligodendrocyte development, Proc. Natl. Acad. Sci. USA 83:822 (1986).PubMedCrossRefGoogle Scholar
  48. 48.
    R. H. M. van der Pal, J. W. Koper, L. M. G. van Golde, and M. Lopes-Cardozo, Effects of insulin and insulin-like growth factor (IGF-I) on oligodendrocyte-enriched glial cultures, J. Neurosci. Res. 19:483 (1988).PubMedCrossRefGoogle Scholar
  49. 49.
    Z. G. Xue, N. M. Le Douarin , and J. Smith, Insulin and insulin-like growth factor-I can trigger the differentiation of catecholaminergic precursors in cultures of dorsal root ganglia, Cell Diff. Dev. 25:1 (1988).Google Scholar
  50. 50.
    D. Lenoir and P. Honegger, Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures, Dev. Brain Res. 7:205 (1983).CrossRefGoogle Scholar
  51. 51.
    E. DiCicco-Bloom and I. B. Black, Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts, Proc. Natl. Acad. Sci. USA 85:4066 (1988).PubMedCrossRefGoogle Scholar
  52. 52.
    E. Recio-Pinto and D. Ishi, Effects of insulin, insulin-like growth factor-II and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells, Brain Res. 302:323 (1984).PubMedCrossRefGoogle Scholar
  53. 53.
    I. K. Andersson, D. Edwall, G. Norstedt, B. Rozell, A. Slottner and H.- A. Hansson, Differing expression of insulin-like growth factor I in the developing and in the adult rat cerebellum, Acta Physiol Scand 132: 167 (1988).PubMedCrossRefGoogle Scholar
  54. 54.
    D. O. Morgan, J. C. Edman, D. N. Standring, V. A. Fried, M. C. Smith, R. A. Roth, and W. J. Rutter, Insulin-like growth factor II receptor as a multifunctional binding protein, Nature 329:301 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Teresa L. Wood
    • 1
  • Michael Berelowitz
    • 1
  • Jeffrey F. McKelvy
    • 2
  1. 1.Department of Neurobiology and BehaviorSUNY at Stony BrookStony BrookUSA
  2. 2.Abbott LaboratoriesAbbott ParkUSA

Personalised recommendations