Differential Regulation of Tyrosine Amino-Transferase by Glucocorticoids: Transcriptional and Post-Transcriptional Control

  • E. Brad Thompson
  • P. Gadson
  • G. Wasner
  • S. S. SimonsJr.
Conference paper


Current models of steroid hormone action focus on three components: the ligands (steroids) themselves, their receptors, and the cis-active steroid response elements (SRE’s) to which the receptor binds to cause increased or decreased transcriptional activity from nearby genes. Many studies have found that as steroid concentration increases across the range that leads to full occupancy of the receptor, a constant fraction of the steroid-receptor complex becomes more tightly associated with nuclei, presumably interacting with certain SRE’s to effect increasing degrees of response (Baxter et al., 1979). The foundations of these concepts were first established with observations on the induction of tyrosine aminotransferase (E C in HTC cells. This enzyme was one of two that in the late 1950’s had been observed to increase in rat liver in response to glucocorticoid administration (Lin et al., 1957; Lin et al., 1958; Greengard et al.). By establishing a line of liver-derived hepatoma cells (HTC cells), it was possible to resolve clearly several issues not easy to work out in whole animal or whole-organ systems (Thompson et al., 1966). Among these were the fact that in HTC cells, the degree of induction of the transaminase corresponded to the degree of occupancy of the receptor by active glucocorticoids (Baxter et al., 1970; Baxter et al., 1971; Rousseau et al., 1972). This principle was found to hold for a large number of inducible genes, driven by various types of steroids and their receptors.


Glucocorticoid Receptor Glutamine Synthetase Mouse Mammary Tumor Virus Tyrosine Aminotransferase Glucocorticoid Response Element 
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  1. Baxter, J.D. and Rousseau, G.G. Glucocorticoid Receptors. In: Gl ucocorticoid Hormone Action. Baxter, J.D. and Rousseau, G.G. (Eds.), Springer-Verlag, Berlin, Heidelberg, New York, pp. 62–63 (1979).Google Scholar
  2. Baxter, J.D. and Tomkins, G.M. The relationship between glucocorticoid binding and tyrosine aminotransferase induction in hepatoma tissue culture cells. Proc. Natl. Acad. Sci. USA 65:709–715 (1970).PubMedCrossRefGoogle Scholar
  3. Baxter, J.D. and Tomkins, G.M. Specific cytoplasmic glucocorticoid hormone receptors in hepatoma tissue culture cells. Proc.Natl. Acad. Sci. USA 68:932–937 (1971).CrossRefGoogle Scholar
  4. Brock, M.L. and Shapiro, D.J. Estrogen stabilizes vitellogenin mRNA against cytoplasmic degradation. Cell 34:207–214 (1983).PubMedCrossRefGoogle Scholar
  5. Fischer, J.A. and Maniatis, T. Drosophila Adh: a promoter element expands the tissue specificity of an enhancer. Cell 53:451–461 (1988).PubMedCrossRefGoogle Scholar
  6. Gad son, P.G., Simons, S.S., Jr. and Thompson, E.B. Differential induction of tyrosine aminotransferase gene transcription of glucocorticoids in hepatoma cell lines. (Submitted for publication).Google Scholar
  7. Granner, D.K., Sasaki, K. and Chu, D. Multi hormonal regul ation of phosphoenolpyruvate carboxykinase gene transcription, Ann. NY Acad. 478:175–190 (1986).CrossRefGoogle Scholar
  8. Granner, D.K., Thompson, E.B. and Tomkins, G.M. Dexamethasone phosphate-induced synthesis of tyrosine aminotransferase in hepatoma tissue culture cells. J Biol. Chem. 245:1471–1478 (1970).Google Scholar
  9. Greengard, O. and Acs, G. The effect of actinomycin on the substrate and hormonal induction of liver enzymes. Biochim. Biophys. Acta, 61:652–653 (1962).Google Scholar
  10. Jantzen, H.M., Strahle, U., Gloss, B., Stewart, F., Schmid, W., Boshart, M., Miksicek, R. and Schütz, G. Cooperativity of glucoccorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell 49:29–38 (1987).PubMedCrossRefGoogle Scholar
  11. Jassi, R., Salmons, B., Muellenger, D. and Groner, B. The v-mos and h-ras oncogene expression represses glucocorticoid hormone-dependent transcription from the mouse mammary tumor virus LTR. EMBO J... 5:2609–2616 (1986).Google Scholar
  12. Kenney, F.T. Hormonal regulation of synthesis of liver enzymes. In: Mammalian Protein Metabolism, Munro, H.T. (Ed.), Academic Press, New York, pp. 131–150 (1970).Google Scholar
  13. Lee, F., Mulligan, R., Berg, P. and Ringold, G. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumor virus chimeric plasmids, Nature 294:228–232 (1981).PubMedCrossRefGoogle Scholar
  14. Lin, E.C.C. and Knox, W.E. Adaptation of the rat liver tyrosine-aketoglutarate transaminase. Biochim. Bioohys. Acta. 26:85–88 (1957).CrossRefGoogle Scholar
  15. Lin, E.C.C. and Knox, W.E. Specificity of the adaptive response of tyrosine-a-ketoglutarate transaminase in the rat. J. Biol. Chem. 233:1186–1189 (1958).PubMedGoogle Scholar
  16. Loeb, J.N. and Strickland, S. Hormone binding and coupled response relationships in systems dependent on the generation of secondary mediators. Mol. Endo. 1:75–82 (1987).CrossRefGoogle Scholar
  17. Mercier, L., Thompson É B. and Simons, S.S., Jr. Dissociation of steroid binding to receptors and steroid induction of biological activity in a glucocorticoid-responsive cell. Endocrinol 112:601–609 (1983).CrossRefGoogle Scholar
  18. Miller, P.A. and Simons, S. S., Jr. Comparison of glucocorticoid receptors in two rat hepatoma cell lines with different sensitivities to glucocorticoids and ant ig1ucocorticoids. Endocrinol 122:2990–2998 (1988).CrossRefGoogle Scholar
  19. Pfahl, M., Payne, J., Benbrook, D., and Wu, K.C. Differential activation of a hormone-responsive element in various cell lines. In: Steroid Hormone Action (Ed: G. Ringold), Alan R. Liss, New York, pp. 161–168 (1988).Google Scholar
  20. Riegel, A. T., Aitken, S.C., Martin, M.B. and Schoenberg, D.R. Posttranscriptional regulation of albumin gene expression in Xenopus liver: evidence for an estrogen receptor-dependent mechanism. Mol. Endo. 1:160–167 (1987).CrossRefGoogle Scholar
  21. Ringold, G.M. Steroid hormone regulation of gene expression. Ann. Rev, Pharmacol. Toxicol. 25:529–566 (1985).CrossRefGoogle Scholar
  22. Rousseau, G.G., Baxter, J.D. and Tomkins, G.M. Glucocorticoid receptors: relations between steroid binding and biological effects. J. Mol. Biol. 67:99–115 (1972).PubMedCrossRefGoogle Scholar
  23. Scherer, G., Schmid, W. Strange, C.M. Rowckamp, W. and Schütz, G. Isolation of cDNA clones coding for rat tyrosine aminotransferase. Proc. Natl. Acad. Sci. 79:7205–7208 (1982).PubMedCrossRefGoogle Scholar
  24. Schmid, W., Jantzen, M., Mayer, D., Jastorff, B. and Schütz, G. Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes. J Biochem. 165:499–506 (1987).Google Scholar
  25. Schmid, W., Muller, G., Schütz, G. and Gluecksohn-Waelsch, S. Deletions near the albino locus on chromosome 7 of the mouse affect the level of tyrosine aminotransferase mRNA. Prog Natl. Acad. Sci. 82:2866–2869 (1985).CrossRefGoogle Scholar
  26. Schöler, H.R. and Gruss, P. Specific interaction between enhancer-containing molecules and cellular components. Cell 36:403–411 (1984).PubMedCrossRefGoogle Scholar
  27. Simons, S.S., Jr., Miller, P.A., Wasner, G., Miller, N.R. and Mercier, L. Inverse correlation between dexamethasone 21-mesylate agonist activity and sensitivity to dexamethasone for induction of tyrosine aminotransferase in rat hepatoma cells. J Steroid Biochem. 31:1–7 (1988a).CrossRefGoogle Scholar
  28. Simons, S.S., Jr. Mercier, L., Miller, N.R., Miller, P.A., Oshima, H., Sistare, F.D., Thompson, E.B. and Wasner, G. Differential modulation of gene induction by glucocorticoids and antiglucocorticoids in rat hepatoma tissue culture cells. In Press: Cancer Research (1988b).Google Scholar
  29. Steinberg, R.A. and Ivarie, R.D. Posttranscriptional regulation of glucocorticoid-regulated functions. In: Glucocorticoid Hormone Action. (Eds. Baxter, J.D. and Rousseau, G.G.), Springer-Verlag, Berlin, Heidelberg, New York, pp. 291–302 (1979).Google Scholar
  30. Strickland, S. and Loeb, J.N. Obligatory separation of hormone binding and biological response curves in systems dependent upon secondary mediators of hormone action. Proc. Natl. Acad. Sci, USA 78:13661370 (1981).Google Scholar
  31. Strobl, J.S., Dannies, P.S. and Thompson, E.B. Somatic cell hybridization of growth hormone-producing rat pituitary cells and mouse fibroblasts results in extinction of growth hormone expression via a defect in growth hormone RNA production. J. Biol, Chem. 257:6588–6594 (1982).Google Scholar
  32. Thompson, E.B., Tomkins, G.M., and Curran, J.F. Induction of tyrosine alpha-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proc, Natl. Acad. Sci. USA 56:296–303 (1966).CrossRefGoogle Scholar
  33. Thompson, E.B., Granner, D.K., and Tomkins, G.M. Superinduction of tyrosine aminotransferase by actinomycin D in rat hepatoma (HTC) cells. J Mol, Biol. 54:159–175 (1970).CrossRefGoogle Scholar
  34. Tomkins, G.M., Gelehrter, T.D., Granner, D.K., Martin, D., Jr., Samuels, H.H. and Thompson, E.B. Control of specific gene expression in higher organisms. Science 166:1474–1480 (1969).PubMedCrossRefGoogle Scholar
  35. Wasner, G. and Simons, S.S., Jr. Differential sensitivity of HTC and Fu5–5 cells for induction of tyrosine aminotransferase by 3’,5’-cyclic adenosine monophosphate. Mol. Endo. 1:109–120 (1987).CrossRefGoogle Scholar
  36. Wasner, G., Oshima, H., Thompson, E.B., and Simons, S., Jr. Unlinked regulation of the sensitivity of primary glucocorticoid-inducible responses in transfected Fu5–5 rat hepatoma cells. Mol. Endo. 2:1009–1017 (1988).CrossRefGoogle Scholar
  37. Weiss, M.C. and Chaplain, M. Expression of differentiated functions in hepatoma cell hybrids: reappearance of tyrosine aminotransferase inducibility after the loss of chromosomes. Proc. Matl. Acad. Sci. USA 68:3026–3030 (1971).CrossRefGoogle Scholar

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© Springer-Verlag New York, Inc. 1989

Authors and Affiliations

  • E. Brad Thompson
  • P. Gadson
  • G. Wasner
  • S. S. SimonsJr.

There are no affiliations available

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