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Adrenocorticoid action in the spinal cord: Some unique molecular properties of glucocorticoid receptors


  1. 1.

    Glucocorticoid hormones affect several functions of the spinal cord, such as synaptic transmission, biogenic amine content, lipid metabolism, and the activity of some enzymes (ornithine decarboxylase, glycerolphosphate dehydrogenase), indicating that this tissue is a target of adrenal hormones.

  2. 2.

    Corticosterone, the main glucocorticoid of the rat, is detected at all regional levels of the spinal cord, and cold stress increases this steroid, predominantly in the cervical regions.

  3. 3.

    Intracellular glucocorticoid receptors have been found in the spinal cord, with higher concentrations in the cervical and lumbar enlargements. Prima facie, these receptors presented biochemical, stereospecifical, and physicochemical properties similar to those of receptors found in other regions of the nervous system. The prevalent form in the spinal cord is the type II receptor, although type I is also present in small amounts.

  4. 4.

    The type II glucocorticoid receptor of the spinal cord shows an affinity lower (K d 3.5 nM) than that of the hippocampal type II site (K d 0.7 nM) when incubated with [3H]dexamethasone. This condition may impair the nuclear translocation of the spinal cord receptor.

  5. 5.

    Another peculiar property of spinal cord type II site is a greater affinity for DNA-cellulose binding than the hippocampal receptor during heat-induced transformation. Also, the spinal cord receptor shows resistance to the action of RNAse A, an enzyme which increases DNA-cellulose binding of the hippocampal receptor, indicating that both receptors may be structurally different.

  6. 6.

    Therefore, it is possible that a different subclass of type II, or “classical glucocorticoid receptor,” is present in the spinal cord. This possibility makes the cord a useful system for studying diversity of glucocorticoid receptors of the nervous system, especially the relationship between receptor structure and function.

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  1. Beato, M., Kalimi, M., Koustan, M., and Feigelson, P. (1973). Interaction of glucocorticoids with rat liver nuclei. II. Studies on the nature of the cytosol transfer factor and the nuclear acceptor site.Biochemistry 123372–3379.

  2. Birmingham, M. K., Sar, M., and Stumpf, W. E. (1984). Localization of aldosterone and corticosterone in the central nervous system, assessed by quantitative autoradiography.Neurochem. Res. 9333–50.

  3. Chong, M. T., and Lippman, M. E. (1982). Effects of RNA and ribonuclease on the binding of estrogen and glucocorticoid receptors from MCF-7 cells to DNA-cellulose.J. Biol. Chem. 2572996–3002.

  4. Clark, C. R., MacLusky, N. J., and Naftolin, F. (1981). Glucocorticoid receptors in the spinal cord.Brain Res. 217412–415.

  5. Coirini, H., Marusic, E. T., De Nicola, A. F., Rainbow, T. C., and McEwen, B. S. (1983). Identification of mineralocorticoid binding sites in rat brain by competition studies and density gradient centrifugation.Neuroendocrinology 37354–360.

  6. Coirini, H., Magariños, A. M., De Nicola, A. F., Rainbow, T. C., and McEwen, B. S. (1985). Further studies of brain aldosterone binding sites employing new mineralocorticoid and glucocorticoid receptor markersin vitro.Brain Res. 361212–216.

  7. Currie, R. A., and Cidlowski, J. A. (1982). Identification of modified forms of human glucocorticoid receptors during the cell cycle. Endocrinology1102192–2194.

  8. De Fiore, C. H., and Turner, B. B. (1983). (3H)-Corticosterone binding in the caudate-putamen.Brain Res. 27893–101.

  9. De Nicola, A. F., Tornello, S., Weisenberg, L., Fridman, O., and Birmingham, M. K. (1981). Uptake and binding of (3H)-aldosterone by the anterior pituitary and brain regions in adrenalectomized rats.Horm. Metab. Res. 13103–106.

  10. De Nicola, A. F., Ortí, E., Moses, D. F., Magariños, A. M., and Coirini, H. (1987). Functions and dysfunctions of receptors for adrenal steroids in the central nervous system.J. Steroid Biochem. 27599–607.

  11. Do, Y. S., Loose, D. S., and Feldman, D. (1979). Heterogeneity of glucocorticoid binders: A unique and a classical dexamethasone binding sites in bovine tissues.Endocrinology 1051055–1063.

  12. Duncan, G. E., and Stumpfs, W. E. (1984). Target neurons for (3H)-corticosterone in the rat spinal cord.Brain Res. 307321–326.

  13. Economidis, I. V., and Rousseau, G. G. (1985). Association of the glucocorticoid hormone receptor with ribonucleic acid.FEBS 18147–82.

  14. Etgen, A. M., Martin, M., Gilbert, R., and Lynch, G. (1980). Characterization of corticosterone-induced protein synthesis in hippocampal slices.J. Neurochem. 35598–602.

  15. Fuxe, K., Wikstrom, A. C., Okret, S., Agnati, L. F., Harfstrand, A., Yu, Z.-Y., Granholm, I., Zoli, M., Vale, W., and Gustafsson, J.-A. (1985). Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor.Endocrinology 1171803–1812.

  16. Ball, E. D. (1982). Glucocorticoid effects on central nervous excitability and synaptic transmission.Int. Rev. Neurobiol. 23165–195.

  17. Ball, E. D., and Braughler, T. (1981). Acute effects of intravenous glucocorticoid pretreatment on thein vitro peroxidation of cat spinal cord tissue.Exp. Neurol. 73321–324.

  18. Hall, E. D., and McGinley, P. A. (1982). Effects of a single intravenous glucocorticoid dose on biogenic amine levels in cat lumbar spinal cord.J. Neurochem. 391787–1790.

  19. Heller, C. L., Coirini, H., and De Nicola, A. F. (1984). Influence of phosphatase inhibitors and nucleotides on (3H)-dexamethasone binding in cytosol of human placenta.J. Steroid Biochem. 21381–386.

  20. Hutchens, T. W., Markland, F. S., and Hawkins, E. F. (1981). Physicochemical analysis of reversible molybdate effects on different molecular forms of glucocorticoid receptor.Biochem. Biophys. Res. Comm. 10360–67.

  21. Hutchens, T. W., Markland, F. S., and Hawkins, E. F. (1982). RNA induced reversal of glucocorticoid receptor activation.Biochem. Biophys. Res. Comm. 19520–27.

  22. Kaufmann, S. H., and Shaper, J. H. (1984). Binding of dexamethasone to rat liver nucleiin vivo andin vitro: Evidence for two distinct binding sites.J. Steroid Biochem. 20699–708.

  23. Keefer, D. A., Stumpf, W. E., and Sar, M. (1973). Topographical localization of estrogen concentrating cells in the rat spinal cord following3H-estradíol localization.Proc. Soc. Exp. Biol. Med. 143414–417.

  24. Kovacic-Milivojevic, B., La Pointe, M. C., Reker, C. E., and Vedeckis, W. V. (1985). Ribonucleic acid is a component of the oligomeric, transformed mouse AtT-20 cell glucocorticoid receptor.Biochemistry 247357–7366.

  25. Luttge, W. G., and Emadian, S. M. (1988). Further chemical differentiation of type I and type II adrenocorticosteroid receptors in mouse brain cytosol: Evidence for a new class of glucocorticoid receptor.Brain Res. 43541–50.

  26. MacLusky, N. J., Clark, C. R., Shanabrough, M., and Naftolin, F. (1987). Metabolism and binding of androgens in the spinal cord of the rat.Brain Res. 42283–91.

  27. Magariños, A. M., Somoza, G., and De Nicola, A. F. (1987). Glucocorticoid negative feedback and glucocorticoid receptors after hippocampectomy in rats.Horm. Metab. Res. 19105–109.

  28. Magariños, A. M., Estivariz, F., Morano, M. I., and De Nicola, A. F. (1988). Regulation of the central nervous system-pituitary adrenal axis in rats after neonatal treatment with monosodium glutamate.Neuroendocrinology 48105–111.

  29. Marver, D. (1980). Aldosterone action in target epithelia.Vitam. Horm. 3857–117.

  30. McEwen, B. S. (1988). Steroid hormones in brain: Linking “nature” and “nurture.”Neurochem. Res. (in press).

  31. McEwen, B. S., Lambdin, L. T., Rainbow, T. C., and De Nicola, A. F. (1986a). Aldosterone effects on salt appetite in adrenalectomized rats.Neuroendocrinology 4338–43.

  32. McEwen, B. S., De Kloet, E. R., and rostene, W. (1986b). Adrenal steroid receptors and actions in the nervous system.Physiol. Rev. 661121–1188.

  33. Meaney, M. J., and Aitken, D. H. (1985). (3H)-Dexamethasone binding in rat frontal cortex.Brain Res. 328176–182.

  34. Meyer, J. S., Leveille, P. J., De Vellis, J., Gewrlach, J. L., and McEwen, B. S. (1982). Evidence for glucocorticoid target cells in the rat optic nerve: Hormone binding and glycerolphosphate dehydrogenase induction.J. Neurochem. 39423–434.

  35. Morrel, J. I., Wolinsky, T. D., Krieger, M. S., and Pfaff, D. W. (1982). Autoradiographic identification of estradiol-concentrating cells in the spinal cord of the female rat.Exp. Brain Res. 45144–150.

  36. Moses, D. F., Ortí, E., and De Nicola, A. F. (1987). A comparison of the glucocorticoid receptor system in the spinal cord and hippocampus.Brain Res. 408118–124.

  37. Moses, D. F., Gonzalez, S., Ortí, E., and De Nicola, A. F. (1989). Heterogeneity and properties of transformation of corticosteroid receptors in spinal cord and hippocampus.Brain Res. 481317–324.

  38. Ortí, E., Tornello, S., and De Nicola, A. F. (1985a). Dynamic aspects of glucocorticoid receptors in the spinal cord of the rat.J. Neurochem. 451699–1707.

  39. Ortí, E., Coirini, H., and De Nicola, A. F. (1985b). Properties and distribution of glucocorticoid binding sites in cytosol of the spinal cord.Neuroendocrinology 40225–231.

  40. Ortí, E., Magariños, A. M., and De Nicola, A. F. (1986). Evidence of high affinity, stereoselective binding sites for (3H)-aldosterone in the spinal cord.Neuroendocrinology 43404–409.

  41. Ortí, E., Moses, D. F., Grillo, C., and De Nicola, A. F. (1987). Glucocorticoid regulation of glycerolphosphate dehydrogenase and ornithine decarboxylase activities in the spinal cord of the rat.J. Neurochem. 48425–431.

  42. Palkovits, M. (1973). Isolated removal of hypothalamic or other brain nuclei of the rat.Brain Res. 59449–450.

  43. Reid, F. A., Gasc, J.-M., Stumpf, W. E., and Sar, M. (1981). Androgen target cells in spinal cord, spinal ganglion and glycogen body of chick embryos.Exp. Brain Res. 44243–248.

  44. Reul, J. M. H. M., and De Kloet, E. P. (1985). Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation.Endocrinology 1172502–2511.

  45. Reul, J. M. H. M., van der Bosch, F. R., and De Kloet, E. R. (1987). Relative occupation of type I and type II corticosteroid receptors in rat brain following stress and dexamethasone treatment: Functional implications.J. Endocrinol. 115459–467.

  46. Rossini, G. P. (1985). RNAse effects on sedimentation and DNA-binding properties of dexamethasone-receptor complexes from HeLa-cell cytosol.J. Steroid Biochem. 2247–56.

  47. Sar, M., and Stumpf, W. E. (1977). Androgen concentration in motor neurons of cranial nerves and spinal cord.Science 19777–79.

  48. Schmidt, T. J., and Litwack, G. (1982). Activation of the glucocorticoid-receptor complex.Physiol. Rev. 621131–1192.

  49. Simons, S. S., Martinez, H. M., Garcea, R. L., Baxter, J. D., and Tomkins, G. M. (1976). Interactions of glucocorticoid-receptor complexes with acceptor sites.J. Biol. Chem. 251334–343.

  50. Stumpf, W. E., and Sar, M. (1979). Glucocorticosteroid and mineralocorticosteroid hormone target sites in the brain: Autoradiographic studies with corticosterone, aldosterone and dexamethasone. In Jones, M. T., Gillham, B., Dallman, M. F., and Chattopadhyay, S. (eds.),Interaction Within the Brain-Pituitary-Adrenocortical System, Academic Press, London, pp. 137–147.

  51. Towle, A. C., and Sze, P. Y. (1982). (3H)-Corticosterone binding in rat superior cervical ganglion.Brain Res. 253221–229.

  52. Tymoczko, J. L., and Phillips, M. H. (1983). The effects of ribonuclease on rat liver dexamethasone receptor: Increased affinity for deoxyribonucleic acid and alternated sedimentation profile.Endocrinology 112142–149.

  53. Warembourg, M. (1985). Steroid receptors in the brain: Topography and some functional implications.Neurochem. Int. 7941–952.

  54. Weil, C. (1986). Characterization of glucocorticoid receptors in whole and cellular subfractions of embryonic chick spinal cord.Dev. Brain Res. 27167–173.

  55. Wrange, O., and Yu, Z.-Y. (1983). Mineralocorticoid receptors in rat kidney and hippocampus: Characterization and quantitation by isoelectric focusing.Endocrinology 113243–250.

  56. Yamamoto, K. R. (1985). Steroid receptor regulated transcription of specific genes and gene networks.Annu. Rev. Genet. 19209–252.

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De Nicola, A.F., Moses, D.F., González, S. et al. Adrenocorticoid action in the spinal cord: Some unique molecular properties of glucocorticoid receptors. Cell Mol Neurobiol 9, 179–192 (1989).

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Key words

  • corticosterone
  • dexamethasone
  • central nervous system
  • rat
  • stress
  • hippocampus