Skip to main content
Log in

Localization of aldosterone and corticosterone in the central nervous system, assessed by quantitative autoradiography

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Nuclear localization of tritiated aldosterone in the CNS was studied in rats by numerical evaluation of silver grains, deposited over neuronal cell nuclei in thawmounted autoradiograms, and compared with the localization obtained after prior administration of a 100-fold excess of radioinert aldosterone, corticosterone or 18-hydroxy-11-deoxycorticosterone (18-OH-DOC). Corticosterone and 18-OH_DOC completely prevented nuclear localization in most regions examined. However, in contrast to pretreatment with aldosterone, pretreatment with corticosterone and 18-OH-DOC did not completely prevent the concentration of radio-activity in the cell nuclei of the indusium griseum. Traces of radioactivity were, furthermore, retained in areas CA1 and CA2 and the dentate gyrus in rats exposed to corticosterone, but not to 18-OH-DOC, prior to [3H]aldosterone. A similar profile of silver grain distribution to that noted with aldosterone was found for corticosterone except that with tritiated corticosterone the most intense concentration of radioactivity occurred in hippocampal areas CA1 and CA2 and not in the indusium griseum. Prior administration of excess deoxycorticosterone acetate abolished nuclear accumulation of tritiated corticosterone. Dihydrotestosterone, on the other hand, failed to compete with tritiated corticosterone at a dose 200-fold in excess of the tritiated steroid.

We conclude that (1) a receptor readily shared by aldosterone, corticosterone, 18-OH-DOC and DOC, but not by dihydrotestosterone, is widely distributed throughout the CNS, (2) a receptor shared by aldosterone and 18-OH-DOC, but not by corticosterone may be present in hippocampal areas CA1 and CA2, (3) that both these as well as the receptor accepting dihydrotestosterone can be located within the same cell.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. McEwen, B. S., Weiss, J. M., andSchwartz, L. S. 1969. Uptake of corticosterone by rat brain and its concentration by certain limbic structures. Brain Res. 16:227–241.

    Google Scholar 

  2. Waremburg, M. 1975. Radioautographic study of the rat brain after injection of 1,2-3H-corticosterone. Brain Res. 89:61–70.

    Google Scholar 

  3. Stumpf, W. E., andSar, M. 1975. Anatomical distribution of corticosterone-concentrating neurons in rat brain. Pages 254–261in Stumpf, W. E., andGrant, L. D. (eds.), Anatomical Neuroendocrinology, S. Karger AG, Basel.

    Google Scholar 

  4. Ermisch, A., andRÜhle, M. J. 1978. Autoradiographic demonstration of aldosterone-concentrating neuron populations in rat brain. Brain Res. 147: 154–158.

    Google Scholar 

  5. Birmingham, M. K., Stumpf, W. E., andSar, M. 1979. Nuclear localization of aldosterone in rat brain cells assessed by radioautography. Experientia 35:1240–1241.

    Google Scholar 

  6. Anderson, N. S., andFanestil, D. D. 1976. Corticoid receptors in rat brain: evidence for an aldosterone receptor. Endocrinology 98:678–684.

    Google Scholar 

  7. Moguilewsky, M., andRaynaud, J. P. 1980. Evidence for a specific mineralocorticoid receptor in rat pituitary and brain. J. Steroid Biochem. 12:309–314.

    Google Scholar 

  8. De Nicola, A. F., Fridman, O., Weisenberg, L., andBirmingham, M. K. 1981. Uptake and binding of3H-aldosterone by the anterior pituitary and brain regions in adrenalectomized rats. Horm. and Metabol. 13:103–106.

    Google Scholar 

  9. Veldhuis, H. D., Van Koppen, C., Van Ittersum, M. B., andDe Kloet, E. R. 1982. Specificity of the adrenal steroid receptor system in rat hippocampus. Endocrinology 110:2044–2051.

    Google Scholar 

  10. Bartova, A. 1979. Endogenous levels of 18-OH-DOC and related steroids in the brain., Pages 213–220in Jones, M. T., Gillham, B., Dallman, M. F., Chattopadhyay, S. (eds.), Interaction within the Brain-Pituitary-Adrenocortical System, Academic Press.

  11. Birmingham, M. K., andWard, P. J. 1961. The identification of the Porter-Silber chromogen secreted by the rat adrenal. J. Biol. Chem. 236:1661–1667.

    Google Scholar 

  12. Péron, F. G. 1960. Isolation of 18-hydroxydeoxycorticosterone from rat adrenals. Endocrinology 69:39–45.

    Google Scholar 

  13. Tuck, M. T., Chandler, D. W., andMayes, D. M. 1977. The influence of ACTH, dietary sodium upright posture and angiotensin II on plasma 18-hydroxy-11-deoxycorticosterone levels in normal subjects. J. Clin. Endocrinol. Metab. 45:893–902.

    Google Scholar 

  14. Campen, T. J., andFanestil, D. D. 1981. Urinary Na+:K+ ratio is inaccurate index of mineralocorticoid activity. Clinical Research 29:458A.

    Google Scholar 

  15. Brecher, P. I., Pyun, H. Y., andChobanian, A. V. 1974. Studies on the Angiotensin II receptor in the zona glomerulosa of the adrenal gland. Endocrinology 95:1026–1033.

    Google Scholar 

  16. Lucis, R., Carballeira, A., andVenning, E. H. 1965. Biotransformation of Progesterone-414C and 11-deoxycorticosterone-414C by rat adrenal glands in vitro. Steroids 6:737–756.

    Google Scholar 

  17. De Nicola, A. F., andDahl, V. 1971. Acute effects of SU-4885 and its reduced derivative (SU-5236) on the adrenocortical secretion of the rat. Endocrinology 89:1236–1241.

    Google Scholar 

  18. Davis, J. O. 1975. Regulation of aldosterone secretion. Pages 77–106in R. O. Greep andE. B. Astwood, (Section eds.),H. Blaschko, G. Sayers, A. D. Smith, (Volume eds.),S. R. Geiger, (Executive ed.), Handbook of Physiology. Section 7: Endocrinology Vol. VI. Adrenal Gland. American Physiological Society, Washington, D.C.

    Google Scholar 

  19. Hepp, R., Grillet, C., Peytremann, A. andVallotton, M. B. 1977. Stimulation of corticosteroid biosynthesis by angiotensin I, (Des-Asp')-angiotensin I, angiotensin II and (Des-Asp')-angiotensin II in bovine adrenal fasciculata cells. Endocrinology 101:717–725.

    Google Scholar 

  20. Pappius, H. M. andMcCann, W. P. 1969. Effects of steroids on cerebral edema in rats. Arch. Neurol. 20:207–216.

    Google Scholar 

  21. Schmieder, P., Baethmann, A., Schneider, E., Oettinger, W., Enzenbach, R., Marguth, F., andBrendel, W. 1972. The effect of aldosterone and an alsosterone-antagonist on the metabolism and perifocal brain edema in man. Pages 203–210in H. J. Reulen, andK. Schürmann (eds.). Steroids and brain edema, Springer-Verlag, New York, Heidelberg, Berlin.

    Google Scholar 

  22. Birmingham, M. K., Kraulis, I., andTraikov, H. 1974. Steroid-mediated alterations in pituitary-adrenal function. Pages 315–339in M. J. Fregly, andM. S. Fregly (eds.), Oral contraceptives and high blood pressure. Dolphin Press, Gainesville.

    Google Scholar 

  23. Kraulis, I., Traikov, H., Li, M. P., andBirmingham, M. K. 1973. The effects of corticosterone, 18-OH-DOC, DOC and 11β-hydroxyprogesterone on the adrenal pituitary axis of the stressed rat. J. Steroid Biochem. 4:129–137.

    Google Scholar 

  24. Stumpf, W. E. 1976. Techniques for the autoradiography of diffusible compounds. Pages 171–193in D. M. Prescott (ed.), Methods in cell biology XIII, Academic Press, New York.

    Google Scholar 

  25. Koenig, J. F. R., andKlippel, R. A. 1974. The rat brain: A stereotaxic atlas of the forebrain and lower parts of the brain stem. Robert E. Krieger Publishing Co. Inc., Huntington, New York 11743.

    Google Scholar 

  26. Stumpf, W. E., andSar, M. 1979. Glucocorticosteroid and mineralocorticosteroid hormone target sites in the brain: Autoradiographic studies with corticosterone, aldosterone and dexamethasone. Pages 137–147,in M. T. Jones, M. F. Dallman, B. Gillham andS. Chattopadhyay (eds.), Interactions within the brain-pituitary-adrenocortical system, Academic Press, New York.

    Google Scholar 

  27. Heritage, A. S., Grant, L. D., andStumpf, W. E. 1977. [3H]Estradiol in catecholamine neurones of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence. J. Comp. Neurol. 176:607–630.

    Google Scholar 

  28. Sar, M., andStumpf, W. E. 1977. Distribution of androgen target cells in rat forebrain and pituitary after [3H]dihydrotestosterone administration. J. Steroid Biochem. 8:1131–1135.

    Google Scholar 

  29. Stumpf, W. E. andSar, M. 1973. Hormonal inputs to releasing factor cells feedback sites. Pages 53–71in W. H. Gispen, E. Zimmerman, B. H. Marks, andD. de Wied (eds.), Progress in brain research, Vol. 39, Elsevier Publ. Co., Amsterdam.

    Google Scholar 

  30. McEwen, B. S., andWallach, G. 1973. Corticosterone binding to hippocampus: nuclear and cytosol binding in vitro. Brain Res. 57:373–386.

    Google Scholar 

  31. Porter, G. A., andKimsey, J. 1971. Assessment of the mineralocorticoid activity of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in the isolated toad bladder. Endocrinology 89:353–357.

    Google Scholar 

  32. Beauwens, R., Birmingham, M., andCrabbé, J. 1983. Stimulation of sodium transport by toad skin incubated with natural derivatives of corticosterone and deoxycorticosterone. J. Endocrinol. 99:293–300.

    Google Scholar 

  33. Funder, J. W., Feldman, D., andEdelman, I. S. 1973. The roles of plasma binding and receptor specificity in the mineralocorticoid action of aldosterone. Endocrinology 92:994–1004.

    Google Scholar 

  34. Fuller, P. J., andFunder, J. W. 1976. Tritiated 18-hydroxydeoxycorticosterone binding in renal, cardiac and hepatic cytoplasma and in plasma from adrenalectomized rats. J. Steroid Biochem. 7:673–676.

    Google Scholar 

  35. Pardridge, W. M., Sakiyama, R., andJudd, H. L. 1983. Protein-bound corticosteroid in human serum is selectively transported into rat brain and liver in vivo. J. Clin. Endocrinol. Metab. 57:160–165.

    Google Scholar 

  36. Rees, H. D., Stumpf, W. E. andSar, M. 1975. Autoradiographic studies with [3H]dexamethasone in the rat brain and pituitary. Pages 262–269in W. E. Stumpf, andL. D. Grant (eds.), Anatomical Neuroendocrinology, S. Karger, Basel.

    Google Scholar 

  37. Holzbauer, M. 1972. The association of steroids with blood cells in vivo. J. Steroid Biochem. 3:579–592.

    Google Scholar 

  38. Pasqualini, J. R., andSumida, C. 1977. Mineralocorticoid receptors in target tissues. Pages 399–511in J. R. Pasqualini (ed.), Receptors and mechanism of action of steroid hormone, Marcel Dekker, New York.

    Google Scholar 

  39. Kraulis, I., Foldes, G., Traikov, H., Dubrovsky, B., andBirmingham, M. K. 1975. The distribution, metabolism and biological activity of deoxycorticosterone in the central nervous system. Brain Res. 188:1–14.

    Google Scholar 

  40. McEwen, B. S., De Kloet, E. R., andWallach, G. 1976. Interactions in vivo and in vitro of corticoids and progesterone with cell nuclei and soluble macromolecules from rat brain regions and pituitary. Brain Res. 105:129–136.

    Google Scholar 

  41. Jones, M. T., andTiptaft, E. M. 1977. Structure-activity relationship of various corticosteroids on the feedback control of corticotrophin secretion. Br. J. Pharmacology 59:35–41.

    Google Scholar 

  42. Birmingham, M. K., Oliver, J. T., Bartova, A., Frei, P. andLevy, S. 1979. Secretory patterns of 18-OH-DOC and related steroids and their possible role in hypertension. Pages 197–211in M. T. Jones, B. Gillham, M. F. Dallman, andS. Chattopadhyay (eds.), Interaction within the brain-pituitary-adrenocortical System, Academic Press, London.

    Google Scholar 

  43. Lassman, M. N., andMulrow, P. J. 1973. Deficiency of deoxycorticosterone binding protein in the hypothalamus of rats resistant to deoxycorticosterone-induced hypertension. Endocrinology 94:1541–1546.

    Google Scholar 

  44. Dubrovsky, B., Williams, D., andKraulis, I. 1982. Effects of deoxycorticosterone and its Ring A-reduced derivatives on the nervous system. Exp. Neurology 78:728–739.

    Google Scholar 

  45. Barbas, H., Kraulis, I., andDubrovsky, B. 1976. Effects of corticosteroid and 5α-dihydrocorticosterone on brain stem sciatic evoked potentials. Soc. Neurosci. Abst. 2, 664.

    Google Scholar 

  46. Dubrovsky, B., Illes, J., andBirmingham, M. K. 1982. Effect of 18-hydroxydeoxycorticosterone on CNS excitability. The Endocrine Society, 64th Annual Meeting, San Francisco, Abst. 1169, p. 372.

    Google Scholar 

  47. Selye, H. 1941. Anaesthetic effects of steroid hormones. Proc. Soc. Exp. Biol. (N.Y.) 46:116–121.

    Google Scholar 

  48. P'An, S. Y., andLaubach, G. D. 1964. Steroid central depressants. Pages 415–475in Dorfman (ed.), Methods in hormone research, Vol. III, Academic Press, New York.

    Google Scholar 

  49. Jones, M. T., Gillham, B., Mahmoud, S., andHolmes, M. C. 1979. The characteristics and mechanism of action and corticosteroid negative feedback at the hypothalamus and anterior pituitary. Pages 163–180in M. T. Jones, B. Gillham, M. F. Dallman, andS. Chattopadhyay (eds.), Interaction within the brain-pituitary-adrenocortical system, Academic Press, London.

    Google Scholar 

  50. Dallman, M. F. 1979. Adrenal feedback on stress-induced corticoliberin (CRF) and corticotropin (ACTH) secretion. Pages 149–162in M. T. Jones, B. Gillham, M. F. Dallman, andS. Chattopadhyay (eds.), Interaction within the brain-pituitary-adrenocortical system, Academic Press, London.

    Google Scholar 

  51. Pappius, H. M. 1980. Mapping of cerebral functional activity with radioactive deoxyglucose. Application in studies on traumatized brain. Pages 271–279in J. Cervos-Navarro andR. Ferszt (eds.), Advances in neurology, Raven Press, New York.

    Google Scholar 

  52. Bartova, A., Tibagong, M., andBirmingham, M. K. 1971. Steroid-mediated stimulation of aerobic glycolysis by intact mouse adrenal glands in vitro. Endocrinology 89:1142–1151.

    Google Scholar 

  53. Bartova, A., andBirmingham, M. K. 1971. The stimulation in vitro of lactic acid production by rodent adrenal glands. Effects of glucose, ACTH, 3′5′-cyclic AMP, ouabain, potassium, anaerobiosis and corticosterone. Endocrinology 88:845–856.

    Google Scholar 

  54. McIlwain, H., andTresize, M. A. 1956. The glucose, glycogen and aerobic glycolysis of isolated cerebral tissues. Biochem. J. 63:250–257.

    Google Scholar 

  55. Dickens, F., andGreville, G. D. 1935. The metabolism of normal and tumour tissue. XIII. Neutral salt effects. Biochem. J. 29:1468–1483.

    Google Scholar 

  56. Elliott, K. A. C., andBilodeau, F. 1962. The influence of potassium on respiration and glycolysis by brain slices. Biochem. J. 84:421–428.

    Google Scholar 

  57. Spray, D. C., Harris, A. L., andBennett, M. V. C. 1981. Gap junctional conductance is a simple and sensitive function of intracellular pH. Science 211:712–714.

    Google Scholar 

  58. Elliott, K. A. C., andBirmingham, M. K. 1949. The effect of pH on the respiration of brain tissue; the pH of tissue slices. J. Biol. Chem. 177:51–58.

    Google Scholar 

  59. Birmingham, M. K., andElliott, K. A. C. 1951. Effects of pH, bicarbonate and cofactors on the metabolism of brain suspensions. J. Biol. Chem. 189:73–86.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dedicated to K. A. C. Elliott on his 80th birthday.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Birmingham, M.K., Sar, M. & Stumpf, W.E. Localization of aldosterone and corticosterone in the central nervous system, assessed by quantitative autoradiography. Neurochem Res 9, 333–350 (1984). https://doi.org/10.1007/BF00963982

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00963982

Keywords

Navigation