Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 May 15;212(2):305–312. doi: 10.1042/bj2120305

No correlation between binding of glucocorticosteroids to specific cytoplasmic proteins in vivo and enzyme induction in the rat liver.

H Grote, J Voigt, C E Sekeris
PMCID: PMC1152048  PMID: 6136271

Abstract

Time- and dose-dependence of the formation of the different cytoplasmic hormone-protein complexes were studied in the rat liver after administration in vivo of [3H]cortisol or [3H]dexamethasone and compared with the stimulation of RNA polymerase B and induction of tyrosine aminotransferase and tryptophan oxygenase. No correlation could be found between formation in vivo of any of the five cytoplasmic hormone-protein complexes found and stimulation of RNA polymerase B activity or enzyme induction. After administration of [3H]cortisol, different metabolites of cortisol could be demonstrated in the isolated hormone-protein complexes. No time- or dose-dependence of the metabolite patterns could be observed after application of hormone doses that were in the range of the biologically active doses. After administration of [3H]dexamethasone, the same hormone-protein complexes were observed, which contained, however, the injected steroid instead of metabolites. These results seem to indicate that the cytoplasmic binding components present in the rat liver are enzymes involved in the metabolism of the glucocorticosteroids and that dexamethasone binds to these enzymes as a substrate analogue.

Full text

PDF
305

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baxter J. D., Tomkins G. M. Specific cytoplasmic glucocorticoid hormone receptors in hepatoma tissue culture cells. Proc Natl Acad Sci U S A. 1971 May;68(5):932–937. doi: 10.1073/pnas.68.5.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beato M., Biesewig D., Braendle W., Sekeris C. E. On the mechanism of hormone action. XV. Subcellular distribution and binding of (1,2-3H)cortisol in rat liver. Biochim Biophys Acta. 1969 Dec 30;192(3):494–507. doi: 10.1016/0304-4165(69)90399-7. [DOI] [PubMed] [Google Scholar]
  4. Beato M., Feigelson P. Glucocorticoid-binding proteins of rat liver cytosol. I. Separation and identification of the binding proteins. J Biol Chem. 1972 Dec 25;247(24):7890–7896. [PubMed] [Google Scholar]
  5. Beato M., Kalimi M., Feigelson P. Correlation between glucocorticoid binding to specific liver cytosol receptors and enzyme induction in vivo. Biochem Biophys Res Commun. 1972 Jun 28;47(6):1464–1472. doi: 10.1016/0006-291x(72)90237-9. [DOI] [PubMed] [Google Scholar]
  6. Beato M., Schmid W., Braendle W., Sekeris C. E. Partial purification of a cortisol binding protein from rat liver cytosol. Steroids. 1970 Aug;16(2):207–216. doi: 10.1016/s0039-128x(70)80106-4. [DOI] [PubMed] [Google Scholar]
  7. Beato M., Schmid W., Sekeris C. E. Two cortisol binding proteins from rat liver cytosol. Biochim Biophys Acta. 1972 May 18;263(3):764–774. doi: 10.1016/0005-2795(72)90060-8. [DOI] [PubMed] [Google Scholar]
  8. Bulanyi G. S., Oliver I. T. Cytosol protein aggregation and dexamethasone binding to isolated rat liver nuclei. FEBS Lett. 1976 Nov;70(1):33–36. doi: 10.1016/0014-5793(76)80720-x. [DOI] [PubMed] [Google Scholar]
  9. CHAMBERLIN M., BERG P. Deoxyribo ucleic acid-directed synthesis of ribonucleic acid by an enzyme from Escherichia coli. Proc Natl Acad Sci U S A. 1962 Jan 15;48:81–94. doi: 10.1073/pnas.48.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CLELAND W. W. The kinetics of enzyme-catalyzed reactions with two or more substrates or products. II. Inhibition: nomenclature and theory. Biochim Biophys Acta. 1963 Feb 12;67:173–187. doi: 10.1016/0006-3002(63)91815-8. [DOI] [PubMed] [Google Scholar]
  11. Carlstedt-Duke J., Gustafsson J. A., Gustafsson S. A. Sexual differences in hepatic metabolism and intracellular distribution of corticosterone studied by pulse labeling with (1,2,6,7-3H)corticosterone. Biochemistry. 1975 Feb 11;14(3):639–648. doi: 10.1021/bi00674a028. [DOI] [PubMed] [Google Scholar]
  12. Carlstedt-Duke J., Gustafsson J. A., Gustafsson S. A., Wrange O. Interactions of corticosterone, 5alpha-dihydrocorticosterone and dexamethasone with proteins in rat-liver cytosol. Eur J Biochem. 1977 Feb 15;73(1):231–238. doi: 10.1111/j.1432-1033.1977.tb11311.x. [DOI] [PubMed] [Google Scholar]
  13. GARREN L. D., HOWELL R. R., TOMKINS G. M., CROCCO R. M. A PARADOXICAL EFFECT OF ACTINOMYCIN D: THE MECHANISM OF REGULATION OF ENZYME SYNTHESIS BY HYDROCORTISONE. Proc Natl Acad Sci U S A. 1964 Oct;52:1121–1129. doi: 10.1073/pnas.52.4.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GREENGARD O., SMITH M. A., ACS G. Relation of cortisone and synthesis of ribonucleic acid to induced and developmental enzyme formation. J Biol Chem. 1963 Apr;238:1548–1551. [PubMed] [Google Scholar]
  15. Gehring U., Tomkins G. M. A new mechanism for steroid unresponsiveness: loss of nuclear binding activity of a steroid hormone receptor. Cell. 1974 Nov;3(3):301–306. doi: 10.1016/0092-8674(74)90145-7. [DOI] [PubMed] [Google Scholar]
  16. Govindan M. V. Immunofluorescence microscopy of the intracellular translocation of glucocorticoid-receptor complexes in rat hepatoma (HTC) cells. Exp Cell Res. 1980 Jun;127(2):293–297. doi: 10.1016/0014-4827(80)90435-8. [DOI] [PubMed] [Google Scholar]
  17. Govindan M. V., Sekeris C. E. Purification of two dexamethasone-binding proteins from rat-liver cytosol. Eur J Biochem. 1978 Aug 15;89(1):95–104. doi: 10.1111/j.1432-1033.1978.tb20900.x. [DOI] [PubMed] [Google Scholar]
  18. Grote H., Schmid W., Sekeris C. E. Binding of [3H] dexamethasone to rat liver cytosol proteins during postnatal development. FEBS Lett. 1977 Oct 15;82(2):329–332. doi: 10.1016/0014-5793(77)80613-3. [DOI] [PubMed] [Google Scholar]
  19. Kalimi M., Colman P., Feigelson P. The "activated" hepatic glucocorticoid-receptor complex. Its generation and properties. J Biol Chem. 1975 Feb 10;250(3):1080–1086. [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  21. Litwack G., Filler R., Rosenfield S. A., Lichtash N., Wishman C. A., Singer S. Liver cytosol corticosteroid binder II, a hormone receptor. J Biol Chem. 1973 Nov 10;248(21):7481–7486. [PubMed] [Google Scholar]
  22. Litwack G., Ketterer B., Arias I. M. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature. 1971 Dec 24;234(5330):466–467. doi: 10.1038/234466a0. [DOI] [PubMed] [Google Scholar]
  23. Marković R. D., Litwack G. Activation of liver and kidney glucocorticoid-receptor complexes occurs in vivo. Arch Biochem Biophys. 1980 Jul;202(2):374–379. doi: 10.1016/0003-9861(80)90440-3. [DOI] [PubMed] [Google Scholar]
  24. Morey K. S., Litwack G. Isolation and properties of cortisol metabolite binding proteins of rat liver cytosol. Biochemistry. 1969 Dec;8(12):4813–4821. doi: 10.1021/bi00840a024. [DOI] [PubMed] [Google Scholar]
  25. Munck A., Foley R. Activation of steroid hormone-receptor complexes in intact target cells in physiological conditions. Nature. 1979 Apr 19;278(5706):752–754. doi: 10.1038/278752a0. [DOI] [PubMed] [Google Scholar]
  26. Nickol J. M., Lee K. L., Hollinger T. G., Kenney F. T. Translation of messenger RNA specific for tyrosine aminotransferase in oocytes of Xenopus laevis. Biochem Biophys Res Commun. 1976 Sep 20;72(2):687–693. doi: 10.1016/s0006-291x(76)80094-0. [DOI] [PubMed] [Google Scholar]
  27. Roewekamp W. G., Hofer E., Sekeris C. E. Translation of mRNA from rat-liver polysomes into tyrosine aminotransferase and tryptophan oxygenase in a protein-synthesizing system from wheat germ. Effects of cortisol on the translatable levels of mRNA for these two enzymes. Eur J Biochem. 1976 Nov 1;70(1):259–268. doi: 10.1111/j.1432-1033.1976.tb10977.x. [DOI] [PubMed] [Google Scholar]
  28. Rousseau G. G., Baxter J. D., Higgins S. J., Tomkins G. M. Steroid-induced nuclear binding of glucocorticoid receptors in intact hepatoma cells. J Mol Biol. 1973 Sep 25;79(3):539–554. doi: 10.1016/0022-2836(73)90405-1. [DOI] [PubMed] [Google Scholar]
  29. Rousseau G. G. Interaction of steroids with hepatoma cells: molecular mechanisms of glucocorticoid hormone action. J Steroid Biochem. 1975 Jan;6(1):75–89. doi: 10.1016/0022-4731(75)90032-1. [DOI] [PubMed] [Google Scholar]
  30. Schmid H., Grote H., Sekeris C. E. Stabilization and characterization of the dexamethasone-binding proteins in rat liver cytosol. Mol Cell Endocrinol. 1976 Aug-Sep;5(3-4):223–241. doi: 10.1016/0303-7207(76)90086-1. [DOI] [PubMed] [Google Scholar]
  31. Schutz G., Beato M., Feigelson P. Messenger RNA for hepatic tryptophan oxygenase: its partial purification, its translation in a heterologous cell-free system, and its control by glucocorticoid hormones. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1218–1221. doi: 10.1073/pnas.70.4.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schutz G., Feigelson P. Expression of total enzyme activity by means of thermal activation of hepatic tryptophan oxygenase. Anal Biochem. 1972 Mar;46(1):149–155. doi: 10.1016/0003-2697(72)90406-x. [DOI] [PubMed] [Google Scholar]
  33. Schutz G., Killewich L., Chen G., Feigelson P. Control of the mRNA for hepatic tryptophan oxygenase during hormonal and substrate induction. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1017–1020. doi: 10.1073/pnas.72.3.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sekeris C. E., Niessing J., Seifart K. H. Inhibition by alpha-amanitin of induction of tyrosine transaminase in rat liver by cortisol. FEBS Lett. 1970 Jul 29;9(2):103–104. doi: 10.1016/0014-5793(70)80324-6. [DOI] [PubMed] [Google Scholar]
  35. Steeger J. R., Litwack G. Isolation and characterization of binder IIIA, a new protein which binds corticosteroid anions. Eur J Biochem. 1981;114(1):145–152. doi: 10.1111/j.1432-1033.1981.tb06185.x. [DOI] [PubMed] [Google Scholar]
  36. Voigt J., Grote H., Sekeris C. E. Absence of hydrocortisone from cytoplasmic hormone-protein complexes formed in vivo after administration of biologically active doses of [3H]hydrocortisone. Biochim Biophys Acta. 1981 May 18;674(3):306–318. doi: 10.1016/0304-4165(81)90361-5. [DOI] [PubMed] [Google Scholar]
  37. Voigt J., Köster H. Induction of plasma proangiotensin by steroid hormones in nephrectomized rats. Eur J Biochem. 1980 Sep;110(1):57–65. doi: 10.1111/j.1432-1033.1980.tb04840.x. [DOI] [PubMed] [Google Scholar]
  38. Voigt J., Sekeris C. E. Differences in inducibility by glucocorticoids of rat liver TO and TAT. Am J Physiol. 1978 Oct;235(4):E374–E380. doi: 10.1152/ajpendo.1978.235.4.E374. [DOI] [PubMed] [Google Scholar]
  39. Voigt J., Sekeris C. E. Induction of tryptophan oxygenase and tyrosine aminotransferase by metabolites of hydrocortisone. Biochim Biophys Acta. 1980 Dec 15;633(3):422–435. doi: 10.1016/0304-4165(80)90200-7. [DOI] [PubMed] [Google Scholar]
  40. Voigt J., Sekeris C. E. Influence of the adrenal gland on uptake, retention, metabolism and binding to cytoplasmic proteins of [3H] cortisol by the rat liver. Hoppe Seylers Z Physiol Chem. 1982 Feb;363(2):159–168. doi: 10.1515/bchm2.1982.363.1.159. [DOI] [PubMed] [Google Scholar]
  41. Voigt J., Wieland T., Sekeris C. E. Initial steps in the induction by glucocorticosteroids of rat liver tryptophan oxygenase and tyrosin aminotransferase. Arch Biochem Biophys. 1978 Nov;191(1):101–109. doi: 10.1016/0003-9861(78)90071-1. [DOI] [PubMed] [Google Scholar]
  42. Yamamoto K. R., Stampfer M. R., Tomkins G. M. Receptors from glucocorticoid-sensitive lymphoma cells and two clases of insensitive clones: physical and DNA-binding properties. Proc Natl Acad Sci U S A. 1974 Oct;71(10):3901–3905. doi: 10.1073/pnas.71.10.3901. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES