Studies on the Glucocorticoid Receptor and the Hormonal Modulation of the mRNA for Tryptophan Oxygenase

  • Leelavati Ramanarayanan-Murthy
  • Paul D. Colman
  • Philip Feigelson
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


The important role played by steroid hormones in development and physiological regulation in animals has led investigators over the past few decades to attempt to unravel and understand the molecular mechanisms involved in the function of steroid hormones. Several studies have shown that the steroid hormones, including the glucocorticoid hormone, bind with high affinity to specific receptor proteins in the target cell cytoplasm. The glucocorticoid-receptor complex has been shown to undergo an alteration to an “activated” state which has high affinity for chromosomal sites within the cell nucleus. This glucocorticoid-receptor interaction with the genome accompanies, and is presumed to be responsible for, the cellular responses characteristic of the hormone and its target tissues. The receptor proteins promise to be useful probes in understanding genetic control mechanisms and also the organization and structure of the eukaryotic chromosomes.


Glucocorticoid Receptor Triamcinolone Acetonide Glucocorticoid Hormone Host Liver Morris Hepatoma 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abelev, G.I. (1971) Alpha-fetoprotein in ontogenesis and its asso-ciation with malignant tumors. Adv. in Cancer Res., 14: 295–358.Google Scholar
  2. Anderson, K.M. and Liao, S. (1968) Selective retention of dihydro-testosterone by prostatic nuclei. Nature, 219: 277–279.PubMedCrossRefGoogle Scholar
  3. Baxter, J.D. and Tomkins, G.M. (1970) The relationship between glu-cocorticoid binding and tyrosine aminotransferase induction in hepatoma tissue culture cells. Proc. Nat’l. Acad. Sci. USA, 65: 709–715.Google Scholar
  4. Baxter, J.D., Rousseau, G.G., Benson, M.C., Garcea, R.L., Ito, J. and Tomkins, G.M. (1972) Role of DNA and specific cytoplasmic receptors in glucocorticoid action. Proc. Nat’l. Acad. Sci. USA, 69: 1892–1896.Google Scholar
  5. Beato, M. and Feigelson, P. (1972) Glucocorticoid-binding proteins of rat liver cytosol. 1. Separation and identification of the binding proteins. J. Biot. Chem., 247: 7890–7896.Google Scholar
  6. Beato, M., Kalimi, M., and Feigelson, P. (1972) Correlation be- tween glucocorticoid binding to specific liver cytosol receptors and enzyme induction in vivo. Biochern. Biophys. Res. Commun., 47: 1464–1472.Google Scholar
  7. Beato, M., Kalimi, M., Beato, W., and Feigelson, P. (1974) Inter-action of glucocorticoids with rat liver nuclei: Effect of adrenalectomy and cortisol administration. Endocrinology, 94: 377–387.Google Scholar
  8. Chan, L., Means, A.R., and O’Malley, B.W. (1973) Rates of induc-tion of specific translatable messenger RNAs for ovalbumin and avidin by steroid hormones. Proc. Nat’l. Acad. Sci. USA, 70: 1870–1874.Google Scholar
  9. Colman, P.D. and Feigelson, P. (1976) Purification of the activated glucocorticoid-receptor complex. Mol. Cell Endocrinol., 5: 33–40.Google Scholar
  10. Feigelson, M. and Feigelson, P. (1965) Metabolic effects of glucocorticoids as related to enzyme induction. Advances Enzy. Regul., 3: 11–27.Google Scholar
  11. Feigelson, M., Gross, P., and Feigelson, P. (1962) Early effects of cortisone on nucleic acid and protein metabolism of rat liver. Biochim. Biophys. Acta, 55: 495–504.Google Scholar
  12. Feigelson, P., Beato, M., Colman, P., Kalimi, M., Killewich, L.A., and Schutz, G. (1975) Studies on the hepatic glucocorticoid receptor and on the hormonal modulation of specific mRNA levels during enzyme induction. Rec. Prog. Horm. Res., 31: 213–242.Google Scholar
  13. Feigelson, P., Feigelson, M., and Greengard, 0. (1962) Comparison of the mechanisms of hormonal and substrate induction of rat liver tryptophan pyrrolase. Rec. Prog. Horm. Res., 18: 491–512.Google Scholar
  14. Feigelson, P. and Greengard, 0. (1962) Immunochemical evidence for increased titers of liver tryptophan pyrrolase during substrate and hormonal enzyme induction. J. Biel. Chem., 237: 3714–3717.Google Scholar
  15. Feldman, D., Funder, J.W., and Edelman, I.S. (1972) Subcellular mechanisms in the action of adrenal steroids. Amer. J. Med., 53: 545–560.Google Scholar
  16. Goldstein, L., Stella, E.J., and Knox, W.E. (1962) The effect of hydrocortisone on tyrosine-a-ketoglutarate transaminase and tryptophan pyrrolase activities in the isolated, perfused rat liver. J. Biol. Chem., 237: 1723–1726.Google Scholar
  17. Gorski, J., Toft, D., Shyamala, G., Smith, D., and Notides, A. (1968) Hormone receptors: Studies on the interaction of estrogen with the uterus. Rec. Prog. Horm. Res., 24: 45–80.Google Scholar
  18. Granner, D.K., Hayashi, S., Thompson, E.B., and Tomkins, G.M. (1968) Stimulation of tyrosine aminotransferase synthesis by dexamethasone phosphate in cell culture. J. Mo Z. BioZ., 35: 291–301.Google Scholar
  19. Greengard, O. and Acs, G. (1962) The effect of actinomycin on the substrate and hormonal induction of liver enzymes. Biochim. Biophys. Acta, 61: 652–653.Google Scholar
  20. Hanoune, J. and Feigelson, P. (1969) Turnover of protein and RNA of liver ribosomal components in normal and cortisol-treated rats. Biochim. Biophys. Acta, 199: 214–223.Google Scholar
  21. Haynes, R.C. Jr. (1965) The control of gluconeogenesis by adrenal cortical hormones. Advan. in Enzyme Regul., 3: 111–119.Google Scholar
  22. Jensen, E.V. and DeSombre, E.R. (1973) Estrogen-receptor interaction: Estrogenic hormones effect transformation of specific receptor proteins to a biochemically functional form. Science, 182: 127–134.Google Scholar
  23. Jensen, E.V. and Jacobson, H.I. (1962) Basic guides to the mechan-ism of estrogen action. Rec. Prog. Horm. Res., 18: 387–414.Google Scholar
  24. Kalimi, M., Colman, P., and Feigelson, P. (1975) The “activated” hepatic glucocorticoid-receptor complex: Its generation and properties. J. Biol. Chem., 250: 1080–1086.Google Scholar
  25. Kalimi, M. Beato, M., and Feigelson, P. (1973) Interaction of glu-cocorticoids with rat liver nuclei. 1. Role of the cytosol proteins. Biochemistry, 12: 3365–3371.Google Scholar
  26. Kenney, F.T. (1962) Induction of tyrosine-a-ketoglutarate transaminase in rat liver. IV. Evidence for an increase in the rate of enzyme synthesis. J. Biol. Chem., 236: 3495–3498.Google Scholar
  27. Kenney, F.T. and Flora, R.M. (1961) Induction of tyrosine-a-keto- glutarate transaminase in rat liver. I. Hormonal nature.J. Biol. Chem., 236: 2699–2702.Google Scholar
  28. King, R.J.B. and Mainwaring, W.I.P. (1974) Steroid-ceZZ interactions. Baltimore: University Park Press.Google Scholar
  29. Kitos, P.A., Saxon, G., and Amos, H. (1972) The isolation of poly-adenylate with unreacted cellulose. Biochim. Biophys. Res. Commun., 46: 1426–1437.Google Scholar
  30. Koblinsky, M. (1973) Doctoral Dissertation. Columbia University, New York.Google Scholar
  31. Koblinsky, M., Beato, M., Kalimi, M., and Feigelson, P. (1972) Glucocorticoid-binding proteins of rat liver cytosol. II. Physical characterization and properties of the binding proteins. J. Biol. Chem., 247: 7897–7904.Google Scholar
  32. Koepf, G.F., Horn, H.W., Gemmill, C.L., and Thorn, G.W. (1941) The effect of adrenal cortical hormone on the synthesis of carbo-hydrate in liver slices. Amer. J. Physiol., 135: 175–186.Google Scholar
  33. Long, C.N.H., Katzin, B., and Frey, E.G. (1940) The adrenal cortex and carbohydrate metabolism. Endocrinology, 26: 309–344.CrossRefGoogle Scholar
  34. Mathews, M.B. and Korner, A. (1970) Mammalian cell-free protein synthesis directed by viral ribonucleic acid. Eur. J. Biochim., 17: 328–338.Google Scholar
  35. Mueller, G.C., Herranen, A.M., and Jervell, K.F. (1958) Studies on the mechanism of action of estrogens. Rec. Prog. Horm. Res., 14: 95–139.Google Scholar
  36. O’Malley, B.W. and Means, A.R. (1974) Female steroid hormones and target cell nuclei. Science, 183: 610–620.PubMedCrossRefGoogle Scholar
  37. Palmiter, R.D. and Carey, N.H. (1974) Rapid inactivation of oval-bumin messenger ribonucleic acid after acute withdrawal of estrogen. Proc. Nat’l. Acad. Sci. USA, 71: 2357–2361.Google Scholar
  38. Peterkofsky, B. and Tomkins, G.M. (1967) Effect of inhibitors of nucleic acid synthesis on steroid-mediated induction of tyrosine aminotransferase in hepatoma cell cultures. J. !Vol. Biol., 30: 49–61.Google Scholar
  39. Ramanarayanan-Murthy, L. Colman, P.D., Morris, H.P., and Feigelson, P. (1976) Pretranslational control of tryptophan oxygenaseGoogle Scholar
  40. levels in Morris hepatoma and host liver. Cancer Res., 36: 3594–3599.Google Scholar
  41. Schimke, R.T., Sweeney, E.W., and Berlin, C.M. (1964) An analysis of the kinetics of rat liver tryptophan pyrrolase induction: The significance of both enzyme synthesis and degradation. Biochem. Biophys. Res. Commun., 15: 214–219.Google Scholar
  42. Schutz, G., Beato, M., and Feigelson, P. (1973) Messenger RNA for hepatic tryptophan oxygenase: Its partial purification, its translation in a heterologous cell-free system, and its control by glucocorticoid hormones. Proc. Nat’l. Acad. Sci. USA, 70: 1218–1221.Google Scholar
  43. Schutz, G., Beato, M., and Feigelson, P. (1972) Isolation of eu-karyotic messenger RNA on cellulose and its translocation in vitro. Biochem. Biophys. Res. Commun., 49: 680–689.Google Scholar
  44. Schutz, G., Killewich, L., Chen, G., and Feigelson, P. (1975) Control of the mRNA for hepatic tryptophan oxygenase during hormonal and substrate induction. Proc. Nat’l. Acad. Sci. USA, 72: 1017–1020.Google Scholar
  45. Sippel, A.E., Stavrianopoulos, J.G., Schutz, G., and Feigelson, P. (1974) Translational properties of rabbit globin mRNA after specific removal of poly(A) with ribonuclease H. Proc. Nat’l. Acad. Sci. USA, 71: 4635–4639.Google Scholar
  46. Tomkins, G.M., Gelehrter, T.D., Granner, D, Martin, D. Jr., Samuels, H.H., and Thompson, E.B. (1969) Control of specific gene expression in higher organisms. Expression of mammalian genes may be controlled by repressors acting on the translation of messenger RNA. Science, 166: 1474–1480.Google Scholar
  47. Weinhouse, S. (1972) Glycolysis, respiration, and anomalous gene expression in experimental hepatomas: G.H.A. Clowes Memorial Lecture. Cancer Res., 32: 2007–2016.Google Scholar
  48. Westphal, U. (1971) Steroid-protein interactions. New York: Springer-Verlag, Monographs on Endocrinology, Vol. 4.Google Scholar
  49. Yu, F-L and Feigelson, P. (1969) The sequential stimulation of uracil-rich and guanine-rich RNA species during cortisone induction of hepatic enzymes. Biochem. Biophys. Res. Commun., 35: 499–504.PubMedCrossRefGoogle Scholar
  50. Wong, K.C., Kornel, L., Bezkorovainy, A., and Murphy, B.E.P. 1973 Isolation of cytoplasmic glucocorticoid-binding protein(s) from rat liver by means of affinity chromatography, and its partial characterization. Biochim. Biophys. Acta 328: 133–144.Google Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • Leelavati Ramanarayanan-Murthy
    • 1
  • Paul D. Colman
    • 1
  • Philip Feigelson
    • 1
  1. 1.Institute of Cancer Research & Department of BiochemistryCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA

Personalised recommendations