Advertisement

Insulin-Like Growth Factor Receptors in the Brain

  • Denis G. Baskin
  • Nancy J. Bohannon
  • Dianne P. Figlewicz

Abstract

A growing body of evidence now indicates that the central nervous system (CNS) is a target of peptides from the gut and pancreas. Insulin from the pancreatic islets, for example, enters the brain from the periphery and influences the physiology of the CNS (review by Baskin et al., 1987). The recent appreciation that insulin-like growth factors (IGF’s), peptides with insulin-like structure and biological activity, are also present in the CNS has stimulated a great deal of current interest in brain IGF’s and their possible functions in the CNS. The present article reviews the status of the IGF’s as regulatory peptides in the CNS, and emphasizes recent developments concerning the anatomical location of receptors for IGF’s in the brain.

Keywords

Choroid Plexus Growth Hormone Secretion Median Eminence Quantitative Autoradiography Autoradiographic Image 
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. Abe, H., Molitch, M., Van Wyk, J., and Underwood, L., 1983, Human growth hormone and somatomedin-C suppress the spontaneous release of growth hormone in unanesthetized rats, Endocrinology, 113: 1319.PubMedCrossRefGoogle Scholar
  2. Bâckstrom, M., Hall, K., and Sara, V., 1984, Somatomedin levels in cerebrospinal fluid from adults with pituitary disorders, Acta. Endocrinol., 107: 171.Google Scholar
  3. Baskin, D., Brewitt, B., Davidson, D., Corp, E., Paquette, T., Figlewicz, D., Graham, M., Woods, S., and Dorsa, D., 1986a, Quantitative autoradiographic evidence for insulin receptors in the choroid plexus of the rat brain, Diabetes, 35: 246–249.PubMedCrossRefGoogle Scholar
  4. Baskin, D., Davidson, D., Corp, E., Lewellen, T., and Graham, M., 1986b, An inexpensive microcomputer digital imaging system for densitometry: quantitative autoradiography of insulin receptors with 125I and LKB Ultrofilm, J. Neurosci. Meth., 16: 119.Google Scholar
  5. Baskin, D., and Dorsa, D., 1986, Quantitative autoradiography and in vitro radioligand binding, in: “Functional Mapping in Biology and Medicine: Computer Assisted Autoradiography, Experimental Biology and Medicine, Vol. II”, D. McEachron, ed, Karger, NY, pp. 204–234.Google Scholar
  6. Baskin, D., Figlewicz, D., Woods, S., Porte, D., Jr., and Dorsa, D., 1987, Insulin in the brain, Ann. Rev. Physiol., 49: 335.CrossRefGoogle Scholar
  7. Baskin, D., and Bohannon, N., 1987, Localization of binding sites for insulin-like growth factor II (IGF-II) in rat brain by in vitro quantitative autoradiography, Endocrinology (Suppl.), 120 (in press).Google Scholar
  8. Beaton, G., Sagel, J., and Distiller, L., 1975, Somatomedin activity in cerebrospinal fluid, J. Clin. Endocrinol. Metab., 40: 736–737.Google Scholar
  9. Binoux, M., Faivre-Bauman, A., Lassarre, C., Barret, A., and Tixier-Vidal, A., 1985, Triiodothyronine stimulates production of insulin-like growth factor (IGF) by fetal hypothalamus cells cultured in serum-free medium, Dev. Br. Res., 21: 319.Google Scholar
  10. Binoux, M., Hossenlopp, P., Lassarre, C., and Hardouin, N., 1981, Production of insulin-like growth factors and their carrier by rat pituitary gland and brain explants in culture, FEBS Lett., 124: 178.Google Scholar
  11. Berelowicz, M., Firestone, S., and Frohman, L., 1981a, Effects of growth hormone excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution, Endocrinology, 109: 714.CrossRefGoogle Scholar
  12. Berelowicz, M., Szabo, M., Frohman, L., Firestone, S., Chu, L., and Hintz, R., 1981b, Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and pituitary, Science, 212: 1279.CrossRefGoogle Scholar
  13. Bohannon, N., Corp, E., Wilcox, B., Figlewicz, D., Dorsa, D., and Baskin, D., 1987, Insulin-like growth factor-I (IGF-I) binding in the median eminence of the rat is increased by food restriction, Endocrinology (Suppl.), 120 (in press).Google Scholar
  14. Bohannon, N., Corp, E., Wilcox, B., Porte, Jr. D., Figlewicz, D., and Baskin, D., 1986a, Identification of specific binding sites for insulin-like growth factor-I (IGF-I) in the rat brain by in vitro quantitative autoradiography, Appetite, 7: 243.Google Scholar
  15. Bohannon, N., Figlewicz, D., Corp, E., Wilcox, B., Porte, Jr. D., and Baskin, D., 1986b, Identification of binding sites for an insulin-like growth factor (IGF-I) in the median eminence of the rat brain by quantitative autoradiography, Endocrinology, 119: 943.PubMedCrossRefGoogle Scholar
  16. Brazeau, P., Guillemin, R., Ling, N., Van Wyk, J., and Humbel, R., 1982, Inhibition, by somatomedins of growth hormone secretion stimulated by hypothalamic growth hormone releasing factor (somatocrinin, GRF), or the synthetic peptide hGRP, C. R. Acad. Sci. (D) (Paris), 295–651.Google Scholar
  17. Ceda, G., Hoffman, A., Silverberg, G., Wilson, D., and Rosenfeld, R., 1985, Regulation of growth hormone release from cultured human pituitary adenomas by somatomedins and insulin, J. Clin. Endocrinol. Metab., 60: 1204.Google Scholar
  18. Clemmons, D., and Van Wyk, J., 1984, Factors controlling blood concentrations of somatomedin C Clinics, in: “Endocrinology and Metabolism, Vol. 13, No. 1., Tissue Growth Factors,” W.H. Daughaday, ed., Saunders, NY, pp. 113–144.Google Scholar
  19. Corp, E., Woods, S., Porte, Jr., D., Figlewicz, D., and Baskin, D., 1986, Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography, Neurosci. Lett., 70: 17.Google Scholar
  20. D’Ercole, A., Applewhite, G., and Underwood, L., 1980, Evidence that somatomedin is synthesized by multiple tissues in the fetus, Develop. Biol, 75: 315.Google Scholar
  21. Dorsa, D., and Baskin, D., 1987, Identification of neuropeptide receptors, in: “Advances in Neuromethods,” A. Boulton, ed., Humana Press, Clifton, N.J. (in press).Google Scholar
  22. Ewton, D., Falen, S., and Florini, J., 1987, The type II insulin-like growth-factor (IGF) receptor has low affinity for IGF-I analogs: Pleiotropic actions of IGFs on myoblasts are apparently mediated by the type I receptor. Endocrinology, 120: 115.PubMedCrossRefGoogle Scholar
  23. Figlewicz, D., Baskin, D., Woods, S., and Porte, Jr., D., 1985, Insulin and insulin-like growth factor-I (IGF-I) binding is decreased in the olfactory bulb (OB) but not the cerebral cortex (C) of the obese Zucker (fa/fa) rat. Intl. J. Obesity, 9: 233.Google Scholar
  24. Frank, H., Pardridge, W., Morris, W., Rosenfeld, R., and Choi, T., 1986, Binding and internalization of insulin-like growth factors by isolated brain microvessels, Diabetes, 35: 654.PubMedCrossRefGoogle Scholar
  25. Froesch, E., and Zapf, J., 1985, Insulin-like growth factors and insulin: comparative aspects, Diabetologia, 28: 485.PubMedCrossRefGoogle Scholar
  26. Gammeltoft, S., Hasselbacher, G., Humbel, R. Fehlmann, M., and Van Obberghen, E., 1985, Two types of receptor for insulin-like growth factors in mammalian brain, EMBO J., 4: 3407.Google Scholar
  27. Goodyer, C., de Stephano, L., Lai, W., Guyda, H., and Posner, B., 1984, Characterization of insulin-like growth factor receptors in rat anterior pituitary, hypothalamus, and brain, Endocrinology, 114: 1187.PubMedCrossRefGoogle Scholar
  28. Hasselbacher, G., and Humbel, R., 1982, Evidence for two species of insulin-like growth factor II (IGF-II and “big” IGF-I1) in human spinal fluid, Endocrinology, 110: 1822.CrossRefGoogle Scholar
  29. Hasselbacher, G., Schwab, M., Pasi, A., and Humbel, R., 1985, 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. U.S.A., 82: 2153.Google Scholar
  30. Heidenreich, K., Freidenberg, G., Figlewicz, D., and Gilmore, P., 1986, Evidence for a subtype of insulin-like growth factor I receptor in brain, Reg. Peptides, 15: 301–310.Google Scholar
  31. Lenoir, D., and Honegger, P., 1983, Insulin-like growth factor I (IGF) stimulates DNA synthesis in fetal rat brain cell cultures. Devel Br. Res., 7: 205.Google Scholar
  32. Lauterio, T., Marson, L., Daughaday, W., and Balle, C., 1986, Intracerebroventricular injections of insulin-like growth factor II, but not insulin-like growth factor I, decrease food intake and body weight in rats. Soc. Neurosci. Abstr., 12: 795.Google Scholar
  33. McMorris, F., Smith, T., DeSalvo, S., and Furlanetto, R., 1986, Insulin-growth factor I/Somatomedin C: a potent inducer of oligodendrocyte development, Proc. Natl. Acad. Sci. U.S.A., 83: 822.Google Scholar
  34. Pardridge, W., 1986, Receptor-mediated peptide transport through the blood-brain barrier, Endocrine Rev., 7: 314.Google Scholar
  35. Perkins, S., Eberwine, J., Jansen, M., Hintz, R., Rosenfeld, R., Barchas, J., and Hoffman, A., 1986, Distribution of insulin-like growth factor II messenger RNA in human and rat tissues, Clin. Res., 34:63A.Google Scholar
  36. Rall, L., Falloon, L., Styne D., and Bell, G., 1986, Insulin-like growth factor I and II mRNA are present in numerous tissues of the primate, Clin Res. 34: 135A.Google Scholar
  37. Rosenfeld, R., Ceda, G., Cutler, C., and Hoffman, A., 1985, Insulin and insulin-like growth factor (somatomedin) receptors on cloned rat pituitary tumor cells, Endocrinology, 117: 2008.Google Scholar
  38. Rosenfeld, R., Ceda, G., Wilson, D., Dollar, L., and Hoffman, A., 1985, Characterization of high affinity receptors for insulin and insulin-like growth factors I and II on rat anterior pituitary cells, Endocrinology, 114: 1571.CrossRefGoogle Scholar
  39. Sara, V., Hall, K., von Holz, H., Humbel, R., Sjogren, B., and Wetterberg, L., 1982a, Evidence for the presence of specific receptors for insulin-like growth factors I (IGF-I) and 2 (IGF-2) and insulin throughout the adult human brain, Neurosci. Lett. 34: 39.Google Scholar
  40. Sara, V., Uvnas-Moberg, K., Minas, B., Hall, K., Wetterberg, L., Posloncec, B., and Goiny, M., 1982b, The distribution of somatomedins in the nervous system of the cat and their release following neural stimulation, Acta. Physiol. Scand., 115: 467.Google Scholar
  41. Sara, V., Hall, K., Misaki, M., Fryklund, L., Christensen, N., and Wetterberg, L., 1983, Ontogenesis of somatomedin and insulin receptors in the human fetus, J. Clin. Invest., 71: 1084.Google Scholar
  42. Tannenbaum, G., Guyda, H., and Posner, B., 1983, Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain, Science, 220: 77.PubMedCrossRefGoogle Scholar
  43. Underwood, L., and D’Ercole, A., 1984, Insulin and insulin-like growth factors/somatomedins in fetal and neonatal development, in: “Clinics in Endocrinology and Metabolism Vol. 13, No. 1. Tissue Growth Factors,” W.H. Daughaday, ed., Saunders, NY, pp. 69–89.Google Scholar
  44. Wehrenberg, W., 1986, The role of growth hormone-releasing factor and somatostatin on somatic growth in rats, Endocrinology, 118: 489.PubMedCrossRefGoogle Scholar
  45. Widmer, U., Zapf, J., and Froesch, E., 1984, Insulin-like growth factors and their carrier proteins in cerebrospinal fluid of normals and acromegalics, Abstr. 7th. Int. Congr. Endocrinol., Amsterdam, (Excerpta Med.), p. 1413a.Google Scholar
  46. Woods, S., and Porte, D., Jr., 1983, The role of insulin as a satiety factor in the central nervous system, in: “CNS Regulation of Carbohydrate Metabolism,” A. Szabo, ed., Academic Press, New York, pp. 457–468.Google Scholar
  47. Zapf, J., Schmid, Ch., and Froesch, E., 1984, Biological and immunological properties of insulin-like growth factors (IGF) I and II, in: “Clinics in Endocrinology and Metabolism, Vol. 13, No. 1, Tissue Growth Factors,” W.H. Daughaday, ed., Saunders, NY, pp. 3–30.Google Scholar
  48. Zangger, L, Eberwine, J., Barchas, J., Jansen, J., Rosenfeld, R., Hoffman, A., and Hintz, R., 1986, Tissue distribution of IGF-I mRNA, Clin. Res. 34: 68A.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Denis G. Baskin
    • 1
    • 2
  • Nancy J. Bohannon
    • 1
    • 2
  • Dianne P. Figlewicz
    • 1
    • 2
  1. 1.Veterans Administration Medical CenterSeattleUSA
  2. 2.Departments of Medicine, Biological Structure, and PsychologyUniversity of WashingtonSeattleUSA

Personalised recommendations