, Volume 3, Issue 1, pp 5–12 | Cite as

Selective effects of 8-Br-cAMP on agonists and antagonists of the glucocorticoid receptor

  • Shimin Zhang
  • Mark Danielsen


RU486 has been reported to be a glucocorticoid receptor (GR) and a progesterone receptor (PR) antagonist. We have analysed RU486 activity on the GR in WCL-2 (CHO) cells and in COS-7 cells transiently transfected with the mouse GR and with the reporter MMTVCAT (MCAT). These cell lines do not contain any active progesterone or androgen receptors. In both cell lines RU486 is a partial agonist of the GR with 10–15% of the activity of dexamethasone. As expected, RU486 is also a partial antagonist of the GR. Treatment of COS-7 cells with 8-Br-cAMP increases the agonist activity of both dexamethasone and RU486. This cAMP induced superactivation is seen with all steroids that have full or partial agonist activity. In contrast, the activities of ZK98.299 and R5020, which are complete antagonists of the GR without any agonist activity, are not affected by 8-Br-cAMP treatment. This effect of 8-Br-cAMP is not seen in WCL2 cells. 8-Br-cAMP, therefore, is not a switch which changes antagonists to agonists but is, rather, a cell specific activator of all agonists whether they have full or only partial agonist activity.


glucocorticoid receptor RU486 cyclic AMP 


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  1. Agarwal, M.K., Hainque, B., Moustaid, N. & Lazer, G. (1987).Febs. Lett.,217, 221–226.PubMedCrossRefGoogle Scholar
  2. Arriza, J.L., Weinberger, C., Cerelli, G., Glaser, T.M., Handelin, B.L., Housman, D.E. & Evans, R.M. (1987).Science,237, 268–275.PubMedCrossRefGoogle Scholar
  3. Baulieu, E.-E. (1991).Endocrinol. Metabol. Clin. North Am.,20, 873–891.Google Scholar
  4. Baulieu, E.E. (1989).Science,245, 1351–1357.PubMedCrossRefGoogle Scholar
  5. Beato, M. (1989).Celi,56, 335–344.CrossRefGoogle Scholar
  6. Beck, C.A., Estes, P.A., Bona, B.J., Muro, C.C., Nordeen, S.K. & Edwards, D.P. (1993a).Endocrinology,133, 728–740.PubMedCrossRefGoogle Scholar
  7. Beck, C.A., Weigel, N.L., Moyer, M.L., Nordeen, S.K. & Edwards, D.P. (1993b).Proc. Natl. Acad. Sci. USA,90, 4441–4445.PubMedCrossRefGoogle Scholar
  8. Bell, P.A. & Munck, A. (1973).Biochem. J. 136, 97–107.PubMedGoogle Scholar
  9. Bourgeois, S., Pfahl, M. & Baulieu, E.-E. (1984).EMBO J.,3, 751–755.PubMedGoogle Scholar
  10. Brinkmann, A.O., Faber, P.W., van Rooij H.C., Kuiper, G.G., Ris, C., Klaassen, P., van der Korput, J.A., Voorhorst, M.M., van Laar, J.H., Mulder, E. & Trapman, J. (1989).J. Steroid Biochem. 34, 307–310.PubMedCrossRefGoogle Scholar
  11. Cato, A.C., Miksicek, R., Schütz, G., Arnemann, J. & Beato, M. (1986).EMBO J. 5, 2237–2240.PubMedGoogle Scholar
  12. Chen, C. & Okayama, H. (1987).Mol. Cell. Biol.,7, 2745–2752.PubMedGoogle Scholar
  13. Chrousos, G.P., Laue, L., Nieman, L.K., Kawai, S., Udelsman, R.U., Brandon, D.D. & Loreiaux, D.L. (1988).Kidney Int.,34, S18-S23.CrossRefGoogle Scholar
  14. Danielsen, M. (1991).Nuclear Hormone Receptors, Molecular Mechanisms, Cellular Functions, Clinical Abnormalities, Parker, M. (eds.), Academic Press: London. pp. 39–78.Google Scholar
  15. Danielsen, M., Hinck, L. & Ringold, G.M. (1989).Cell,57, 1131–1138.PubMedCrossRefGoogle Scholar
  16. Danielsen, M., Northrop, J.P. & Ringold, G.M. (1986).EMBO J. 5, 2513–2522.PubMedGoogle Scholar
  17. Evans, R.M. (1988).Science,240, 889–895.PubMedCrossRefGoogle Scholar
  18. Gagne, D., Pons, M. & De-Paulet, A.C. (1986).J. Steroid Biochem.,25, 315–322.PubMedCrossRefGoogle Scholar
  19. Gruol, D.J. & Altschmied, J. (1993).Mol. Endocrinol.,7, 104–113.PubMedCrossRefGoogle Scholar
  20. Hirst, M.A., Northrop, J.P., Danielsen, M., Ringold, G.M. (1990).Mol. Endocrinol.,4, 162–170.PubMedGoogle Scholar
  21. Klein-Hitpass, L., Cato, A.C., Henderson, D. & Ryffel, G.U. (1991).Nucleic Acids Res. 19, 1227–1234.PubMedCrossRefGoogle Scholar
  22. Laue, L., Gallucci, W., Loriaux, D.L., Udelsman, R. & Chrousos, G.P. (1988).J. Clin. Endocrinol. Metab.,67, 602–606.PubMedGoogle Scholar
  23. Mao, M., Regelson, W. & Kalimi, M. (1992).Molec. Cell. Biochem.,109, 1–8.PubMedGoogle Scholar
  24. Mason, S.A. & Housley, P.R. (1993).J. Biol. Chem.,268, 21501–21504.PubMedGoogle Scholar
  25. Moyer, M.L., Borror, K.C., Bona, B.J., DeFranco, D.B., Nordeen, S.K. (1993).J. Biol. Chem.,268, 22933–22940 (1993).PubMedGoogle Scholar
  26. Neef, G., Beier, S., Elger, W., Henderson, D. & Wiechert, R. (1984).Steroids,44, 349–372.PubMedCrossRefGoogle Scholar
  27. Neuman, J.R., Morency, C.A. & Russian, K.O. (1987).Biotechniques,5, 444–447.Google Scholar
  28. Nordeen, S.K., Bona, B.J. & Moyer, M.L. (1993).Mol. Endocrinol.,7, 731–742.PubMedCrossRefGoogle Scholar
  29. Oshima, H. & Simons Jr, S. (1992).Endocrinology,130, 2106–2112.PubMedCrossRefGoogle Scholar
  30. Pratt, W.B. (1993).J. Biol. Chem.,268, 21455–21458.PubMedGoogle Scholar
  31. Price J., Turner, D. & Cepko, C. (1987).Proc. Natl. Acad. Sci. USA,84, 156–160.PubMedCrossRefGoogle Scholar
  32. Quarmby, V.E., Kemppainen, J.A., Sar, M., Lubahn, D.B., French, F.S. & Wilson, E.M. (1990).Mol. Endocrinol.,4, 1399–1407.PubMedCrossRefGoogle Scholar
  33. Rangarajan, P.N., Umesono, K. & Evans, R.M. (1992).A. Mol. Endocrinol.,6, 1451–1457.CrossRefGoogle Scholar
  34. Sartorius, C.A., Tung, L., Takimoto, G.S. & Horwitz, K.B. (1993).J. Biol. Chem.,268, 9262–9266.PubMedGoogle Scholar
  35. Schneider, M.R., Michna, H., Nishino, Y. & E-Etreby, M.F. (1989).Eur. J. Cancer Clin. Oncol.,25, 691–701.PubMedCrossRefGoogle Scholar
  36. Simons Jr, S., Mercier, L., Miller, N.R., Miller, P.A., Oshima, H., Sistare F.D., Thompson, E.B., Wasner, G. & Yen, P.M. (1989).Cancer Res.,49, 2244s-2252s.PubMedGoogle Scholar
  37. Simons Jr, S., Oshima, H. & Szapary, D. (1992).Mol. Endocrinol.,6, 995–1002.PubMedCrossRefGoogle Scholar
  38. Smith, D.F. & Toft, D.O. (1993).Mol. Endocrinol.,7, 4–11.PubMedCrossRefGoogle Scholar
  39. Ulmann, A., Teutsch, G. & Philibert, D. (1990).Sci. Am.,262, 42–48.PubMedCrossRefGoogle Scholar
  40. Umesono, K. & Evans, R.M. (1989).Cell,57, 1139–1146.PubMedCrossRefGoogle Scholar
  41. Webster, N.J., Green, S., Jin, J.R. & Chambon, P. (1988).Cell,54, 199–207.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • Shimin Zhang
    • 1
  • Mark Danielsen
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyGeorgetown University Medical SchoolWashington, DCUSA

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