Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Molecular action of aldosterone

Molekulare Mechanismen der Aldosteron-Wirkung

  • 40 Accesses

  • 15 Citations

Summary

Aldosterone stimulates the reabsorption of sodium across epithelial cells of various target tissues. The initial events in the molecular action of the mineralocorticoid are the following: (1) Diffusion of the steroid across the cellular (baso-lateral, serosal) plasma membrane into the cytoplasmic compartment. (2) Binding of the steroid to a receptor protein specific for the class of steroid and activation of this steroid-receptor-complex. (3) Translocation of the activated aldosterone-receptor complex to the nucleus and stimulation of RNA synthesis (including the synthesis of messenger RNA and ribosomal RNA). (4) Translation of the steroid-induced messenger RNAs at the ribosomal level into the aldosterone-induced proteins (AIP) within the cytoplasmic compartment. Whereas these induction steps are uniformly accepted, the mechanisms by which the AIPs increase the activity of a rate-limiting step in the sodium transport process are still object of debate. In this paper we discuss the initial events in the mode of action of aldosterone and the biochemical and physiological approaches to the aldosterone-induced proteins with special reference to the “sodium permease”, the “energy”, and the “sodium pump” theory. Our analysis shows that despite serious efforts by multiple laboratories, the first AIP with an established relationship to the mineralocorticoid actions of aldosterone is yet to be identified.

Zusammenfassung

Aldosteron stimuliert den aktiven Natrium-Transport in verschiedenen epithelialen Zielorganen. Die initialen molekularen Abläufe sind: (1) Passive Diffusion des Mineralokortikoids von der basolateralen (serösen) Zellseite in das Cytoplasma der Zelle. (2) Bindung des Steroids an spezifische cytoplasmatische Rezeptorproteine mit anschließender Aktivierung des Steroid-Rezeptor-Komplexes. (3) Translokation dieses aktivierten Komplexes zum Nucleus der Zelle und Stimulation der RNS-Syntheses (einschließlich der Synthese von ribosomaler und „messenger“ RNS). (4) Synthese der Aldosteron-induzierten Proteine im Cytoplasma der Zelle. Während diese initialen molekularen Abläufe ausreichend empirisch belegt sind und allgemein akzeptiert werden, besteht weiterhin Unklarheit darüber, wie die Aldosteron-induzierten Proteine die Natrium-Resorption in epithelialen Zielorganen steigern können. In dieser Arbeit werden zunächst die initialen molekularen Mechanismen der Aldosteron-Wirkung diskutiert. Es folgt eine kritische Analyse der bisher erarbeiteten Theorien zur Bedeutung der AIP im Rahmen der Natrium-Regulation in epithelialen Organen. Diese Analyse berücksichtigt sowohl die biochemischen als auch die physiologischen Untersuchungsergebnisse und zeigt, daß trotz zahlreicher Fortschritte die Frage, wie die AIP den Natrium Transport stimulieren, weiterhin unklar bleibt.

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

References

  1. 1.

    Anderson NS III, Fanestil DD (1976) Corticoid receptors in rat brain: Evidence for an aldosterone receptors in rat brain: Evidence for an aldosterone receptor. Endocrinology 98:676–684

  2. 2.

    Ballard PL, Baxter JD, Higgins SJ, Rousseau GG, Tomkins GM (1974) General presence of glucocorticoid receptors in mammalian tissues. Endocrinology 94:998–1002

  3. 3.

    Bojar H, Dreyfurst R, Maar K, Staib W (1977) Distribution of estradiol receptor molecules in human kidney. J Clin Chem Clin Biochem 15:319–321

  4. 4.

    Bullock LP, Bardin CW (1974) Androgen receptors in mouse kidney: A study of male, female and androgeninsensitive (tfm) mice. Endocrinology 94:746–756

  5. 5.

    Chandler JS, Pike JW, Haussler MR (1975) 1,25-Dihydroxyvitamin D3 receptors in rat kidney cytosol. Biochem Biophys Res Commun 90:1057–1063

  6. 6.

    Charney AN, Silva P, Besarab A, Epstein FH (1974) Separate effects of aldosterone, DOCA, and methylprednisolone on renal Na-K-ATPase. Am J Physiol 227:345–350

  7. 7.

    Claire M, Oblin ME, Steimer JL, Nakane H, Misumi J, Michaud A, Corvol P (1981) Effect of adrenalectomy and aldosterone on the modulation of mineralocorticoid receptors in rat kidney. J Biol Chem 256:142–147

  8. 8.

    Colston KW, Feldman D (1979) Demonstration of a 1,25-Dihydroxycholecalciferol cytoplasmatic receptorlike binder in mouse kidney. J Clin Endocrinol Metab 49:798–800

  9. 9.

    De Vries JR, Ludens JH, Fanestil DD (1972) Estradiol renal receptor molecules and estradiol-dependent antinatriuresis. Kidney Internat 2:95–100

  10. 10.

    Doucet A, Katz AL (1981) Short-term effect of aldosterone on Na-K-ATPase in single nephron segments. Am J Physiol 241:F273-F278

  11. 11.

    Edmonds CJ (1972) Effect of aldosterone on mammalian intestine. J Steroid Biochem 3:143–149

  12. 12.

    Fanestil DD (1980) The interaction of hormones with biological membranes. In: Andreoli TE, Hoffman JF, Fanestil DD (Hrsg) Membrane physiology. Plenum Press, New York, p 399

  13. 13.

    Fanestil DD, Edelman IS (1966) Characteristics of the renal nuclear receptors for aldosterone. Proc Natl Acad Sci USA 56:872–879

  14. 14.

    Fanestil DD, Park CS (1981) Steroid hormones and the kidney. Ann Rev Physiol 43:637–649

  15. 15.

    Fazekas AG, Sandor T (1976) The influence of corticosteroids on flavin nucleotide bioxynthesis in rat liver and kidney. J Steroid Biochem 7:29–32

  16. 16.

    Feldman D, Funder J, Loose D (1978) Is the glucocorticoid receptor identical in various target organs. J Steroid Biochem 9:141–145

  17. 17.

    Funder JW, Duval D, Meyer PH, Dahl LK (1974) Mineralocorticoid receptors in salt-susceptible and salt-resistant rats. Endocrinology 94:1739–1743

  18. 18.

    Funder JW, Feldman D, Edelman IS (1972) Specific aldosterone binding in rat kidney and parotid. J Steroid Biochem 3:209–218

  19. 19.

    Funder JW, Feldman D, Edelman IS (1973) The roles of plasma binding and receptor specificity in the mineralocorticoid action of aldosterone. Endocrinology 92:994–1004

  20. 20.

    Funder JW, Feldman D, Edelman IS (1973) Glucocorticoid receptors in rat kidney: The binding of tritiated-dexamethsone. Endocrinology 92:1005–1013

  21. 21.

    Geering K, Rossier BC (1981) Thyroid hormonealdosterone antagonism on Na+ transport in toad bladder. J Biol Chem 256:5504–5510

  22. 22.

    Geheb M, Hercker E, Singer I, Cox M (1981) Subcellular localization of aldosterone induced proteins in toad urinary bladder. Biochim Biophys Acta 641:422–426

  23. 23.

    Gerkin RJ, Sider RS (1981) Aldosterone receptor measurements during changes in dietary sodium. Endocrinol 108:105–112

  24. 24.

    Hendler ED, Torretti J, Kupor L, Epstein FH (1972) Effects of adrenalectomy and hormone replacement on Na-K-ATPase in renal tissue. Am J Physiol 222:754–760

  25. 25.

    Herman TS, Fimognari GM, Edelman IS (1968) Studies on renal aldosterone binding proteins. J Biol Chem 243:3849–3856

  26. 26.

    Katz A, Doucet A (1981) Aldosterone binding along the rabbit nephron. Kidney Internat 19:246

  27. 27.

    Kinne R, Kirsten R (1968) Der Einfluß von Aldosteron auf die Aktivität mitochondrialer und cytoplasmatischer Enzyme in der Rattenniere. Pflügers Arch 300:244–254

  28. 28.

    Kirsten R, Kirsten E (1972) Redox state of pyridine nucleotides in renal response to aldosterone. Am J Physiol 223:229–235

  29. 29.

    Kirsten R, Nelson K, Rüschendorf U, Seger W, Scholz TH, Kirsten E (1977) Effects of aldosterone on lipid metabolism and renal oxygen consumption in the rat. Pflügers Arch 368:189–194

  30. 30.

    Knox WH, Sen AK (1974) Mechanism of action of aldosterone with particular reference to (Na+K)-ATPase. Ann NY Acad Sci 242:471–488

  31. 31.

    Krozowski Z, Funder JW (1981) Mineralocorticoid receptors in the lung. Endocrinology 109:1304–1308

  32. 32.

    Krozowski Z, Funder JW (1981) Mineralocorticoid receptors in rat anterior pituitary: Toward a redifinition of “Mineralocorticoid Hormone”. Endocrinology 109:1221–1224

  33. 33.

    Kusch M, Farman N, Edelman IS (1978) Binding of aldosterone to cytoplasmatic and nuclear receptors of the urinary bladder epithelium of Bufo marinus. Am J Physiol 235:C82-C89

  34. 34.

    Law PY, Edelman IS (1978) Induction of citrate synthase by aldosterone in the rat kidney. J Membr Biol 41:41–64

  35. 35.

    Law PY, Edelman IS (1978) Effect of aldosterone on incorporation of amino acids into renal medullary proteins. J Membr Biol 41:15–40

  36. 36.

    Lin A Y-C, Greengard P (1974) Aldosterone-induced increase in protein phosphatase activity of toad bladder. Proc Natl Acad Sci USA 71:3869–3873

  37. 37.

    Marusic ET, Hayslett JP, Binder HJ (1981) Corticosteroid-binding studies in cytosol of colonic mucosa of the rat. Am J Physiol 240:G417-G423

  38. 38.

    Marver D (1981) Aldosterone receptors in rabbit renal cortex and red medulla Endocrinology 106:611–618

  39. 39.

    Marver D (1980) Aldosterone action in target epithelia. (1980) In: Munson PL, Diczfalusy, Glover J, Olson E (Hrsg) Vitamins and hormones. Academic Press, New York London (Vol. 38, p 557)

  40. 40.

    Marver D, Goodman D, Edelman IS (1972) Relationship between renal cytoplasmatic and nuclear receptors. Kidney Internat 1:210–223

  41. 41.

    Marver D, Stewart J, Funder JW, Feldman D, Edelman IS (1974) Renal aldosterone receptors: Studies with3H-aldosterone and the anti-mineralocorticoid3H-spirolactone (SC-26304). Proc Natl Acad Sci USA 71:1431–1435

  42. 42.

    Matulich DT, Spindler BJ, Schambelan M, Baxter JD (1976) Mineralocorticoid receptors in human kidney. J Clin Endocrinol Metab 43:1170–1174

  43. 43.

    Moguilewsky M, Raynaud JP (1980) Evidence for a specific mineralocorticoid receptor in rat pituitary and brain. J Steroid Biochem 12:309–314

  44. 44.

    Palmer LG, Edelman IS, Lindemann B (1980) Current voltage analysis of apical sodium transport in toad urinary bladder: Effects of inhibitors of transport and metabolism. J Membr Biol 57:59–71

  45. 45.

    Pasqualini JR (1977) Receptors and mechanism of action of steroid hormones. Marcel Decker, New York

  46. 46.

    Reich IM, Skipski IA, Scott WN (1981) Mechanisms of hormonal modulation of ion transport in the toad's urinary bladder. Subcellular localization of aldosterone-induced proteins. Biochim Biophys Acta 776:379–385

  47. 47.

    Rossier BC (1978) Role of RNA in the action of aldosterone on Na+ transport. J Membr Biol 40:187–197

  48. 48.

    Saito T, Essig A, Caplan SR (1973) The effect of aldosterone on the energetics of sodium transport in the frog skin. Biochim Biophys Acta 318:371–382

  49. 49.

    Scott WN, Reich IM, Goodman DBP (1979) Inhibition of fatty acid synthesis prevents the incorporation of aldosterone-induced proteins into membranes. J Biol Chem 254:4957–4959

  50. 50.

    Sheridan PJ, Buchanan JM, Anselmo VC, Martin MM (1979) Equilibrium: The intracellular distribution of steroid receptors. Nature 282:579–582

  51. 51.

    Stoff JS, Handler JS, Preston AS, Orloff J (1973) The effect of aldosterone on cyclic nucleotide phosphodiesterase activity in toad urinary bladder. Life Sci 13:545–552

  52. 52.

    Suzuki S, Ogawa E (1971) Experimental studies on the carbonic anhydrase activity. XV Biochem Pharmacol 20:2191–2204

  53. 53.

    Suzuki S, Ogawa E (1969) Experimental studies on the carbonic anhydrase activity. XII Biochem Pharmacol 18:993–1003

  54. 54.

    Suzuki S, Ogawa E, Inoue Y (1976) Effects of aldosterone, actinomycin D, puromycin and cyclothetimide on RNA synthesis, carbonic anhydrase and ATPase activities of the kidney and on urinary excretion of sodium in adrenalectomized mice. J Steroid Biochem 7:429–438

  55. 55.

    Swaneck GE, Highland E, Edelman IS (1969) Stereospecific nuclear and cytosol aldosterone-binding proteins of various tissues. Nephron 6:297–316

  56. 56.

    Tan EL, Trachewsky D (1974) Effect of aldosterone on flavin coenzyme biosynthesis in the kidney. J Steroid Biochem 6:1471–1475

  57. 57.

    Trachewsky D (1978) Aldosterone stimulation of riboflavin incorporation into rat renal flavin coenzymes and the effect of inhibition by riboflavin analogues on sodium reabsorption. J Clin Invest 62:1325–1333

  58. 58.

    Van de Walle A, Farman N, Beneseth P, Bouvalet JP (1981) Aldosterone binding along the rabbit nephron an autoradiographic study on isolated tubules. Am J Physiol 240:F172-F179

  59. 59.

    Walters MR, Hunziker W, Norman AW (1981) Apparent nuclear localization of unoccupied receptors for 1,25-Dihydroxyvitamin D3. Biochem Biophys Res Comm 98:990–996

  60. 60.

    Wambach G, Higgins JR (1978) Antimineralocorticoid action of progresterone in the rat: Interaction with renal mineralocorticoid receptors. Endocrinology 102:1686–1693

  61. 61.

    Wilce PA, Rossier BC, Edelman IS (1976) Actions of aldosterone on rRNA and Na+ transport in the toad bladder. Biochemistry 15:4286–4292

Download references

Author information

Correspondence to D. D. Fanestil MD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fanestil, D.D., Kipnowski, J. Molecular action of aldosterone. Klin Wochenschr 60, 1180–1185 (1982). https://doi.org/10.1007/BF01716720

Download citation

Key words

  • Aldosterone
  • Molecular action
  • Sodium transport

Schlüsselwörter

  • Aldosteron
  • Molekulare Mechanismen
  • Natrium-Transport