Journal of Endocrinological Investigation

, Volume 19, Issue 8, pp 530–534 | Cite as

Effect of dexamethasone on insulin receptor mRNA levels, RNA stability and isotype RNA pattern in U-937 human promonocytic cells

  • M. A. Leal
  • P. Aller
  • C. Calle
Article

Abstract

The administration of 5×106 mol/l dexamethasone transiently increased insulin receptor (IR) mRNA levels in U-937 human promonocytic cells, which reached the maximum level at 15 h of treatment. Dexamethasone treatment did not affect the IR mRNA half-life (approximately 4 h), suggesting that the increase is regulated at the transcriptional level. The stimulatory action of dexamethasone was not prevented by the simultaneous presence of the protein synthesis inhibitor cycloheximide, indicating that the induction of IR gene transcription occurs as a direct response to the action of the synthetic glucocorticoid. Finally, the A isoform (lacking exon 11) was found to be the only IR isoform present in both untreated and dexamethasone treated-U-937 cells.

Keywords

Insulin receptor gene expression dexamethasone U-937 cells insulin receptor isotypes 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Leal M.A., Aller P., Torres A., Picardo A., Dávila N., Calle C. Insulin receptor mRNA levels are modulated in a tissue-specific manner in Cushing’s syndrome patients. Horm. Metab. Res. 26: 349, 1994.PubMedCrossRefGoogle Scholar
  2. 2.
    Leal M.A., Aller P., Más A., Carranza M.C., Calle C. Tissue-specific changes in insulin receptor mRNA concentrations in dexametasone-treated and adrenalectomized rats. Endocr. J. 41: 737, 1994.PubMedCrossRefGoogle Scholar
  3. 3.
    Leal M.A., Cabanas C., Rius C., Aller P., Calle C. Modulation by dexamethasone of insulin binding and insulin receptor mRNA levels in U-937 human promonocytic cells. Biochimie 74: 545, 1992.PubMedCrossRefGoogle Scholar
  4. 4.
    McDonald A.R., Goldfine I.D. Glucocorticoid regulation of insulin receptor gene transcription in IM-9 cultured lymphocytes. J.Clin. Invest. 81: 499, 1988.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Briata P., Gherzi R. Multifactorial control of insulin receptor gene expression in human cell lines. Biophys. Res. Commun. 170: 1184, 1990.CrossRefGoogle Scholar
  6. 6.
    Levy J.R., Krystal G., Glickman P., Dastvan F. Effects of media conditions, insulin, and dexamethasone on insulin-receptor mRNA and promoter activity in HepG2 cells. Diabetes 40: 58, 1991.PubMedCrossRefGoogle Scholar
  7. 7.
    Sundstrom C., Nilsson K. Establishment and characterization of a human histocytic lymphoma cell line (U-937). Int. J. Cancer 17: 565, 1976.PubMedCrossRefGoogle Scholar
  8. 8.
    Robert A., Grunberger G., Carpentier J.L., Dayer J.M., Orci L., Gorden P. The insulin receptor of a human monocyte-like cell line: characterization and function. Endocrinology 114: 247, 1984.PubMedCrossRefGoogle Scholar
  9. 9.
    Seino S., Bell G.I. Alternative splicing of human insulin receptor messenger RNA. Biophys. Res. Commun. 159: 312, 1989.CrossRefGoogle Scholar
  10. 10.
    Moller D.E., Yokota A., Caro J.F., Flier J.S. Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. Mol. Endocrinol. 3: 1263, 1989.PubMedCrossRefGoogle Scholar
  11. 11.
    Kosaki A., Webster N.J.G. Effect of dexamethasone on the alternative splicing of the insulin receptor mRNA and insulin action in HepG2 hepatoma cells. J. Biol. Chem. 268: 21990, 1993.PubMedGoogle Scholar
  12. 12.
    Norgren S., Luthman H. Regulation of human insulin receptor RNA splicing in HepG2 cells: Effects of glucocorticoid and low glucose concentration. Biophys. Res. Commun. 199: 277, 1994.CrossRefGoogle Scholar
  13. 13.
    Aller P., Rius C., Mata F., Zorrilla A., Cabañas C., Bellón T., Bernabeu C. Camptothecin induces differentiation and stimulates the expression of differentiation related genes in U-937 human promonocytic leukemia cells. Cancer Res. 52: 1245, 1992.PubMedGoogle Scholar
  14. 14.
    Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Lebrach H., Diamond D., Wozney M., Boetzke H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry 16: 4743, 1977.CrossRefGoogle Scholar
  16. 16.
    Hirschhorn R.R., Aller P., Yuan Z.A., Gibson C.W., Baserga R. Cell-cycle specific cDNAs from mammalian cells temperature sensitive for growth. Proc. Natl. Acad. Sci. USA 81: 6004, 1984.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ullrich A., Bell J.R., Chen E.Y., Herrera R., Petruzelli L.M., Dull T.J., Gray A., Coussens L., Liao Y.C., Tsubokawa M., Mason A., Seeburg P.H., Grunfeld C., Rosen O.M., Ramachandran J. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313: 756, 1985.PubMedCrossRefGoogle Scholar
  18. 18.
    Alonso S., Minty A., Borlet Y., Buckingham M. Comparison of three actin-coding sequences in the mouse: evolutionary relationships between actin genes of warmblooded vertebrates. J. Mol. Evol. 23: 1, 1986.CrossRefGoogle Scholar
  19. 19.
    Feinberg A.P., Vogelstein B. A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 137: 266, 1984.PubMedCrossRefGoogle Scholar
  20. 20.
    Iwama N., Nomura M., Kajimoto Y., Imano E., Kubota M., Watarai T., Kawamori R., Shichiri M., Kamada T. Effect of dexamethasone on the synthesis and degradation of insulin receptor mRNA in cultured IM-9 cells. Diabetologia 30: 899, 1987.PubMedGoogle Scholar
  21. 21.
    Rouiller D.G., McKeon C., Taylor S.I., Gorden P. Hormonal regulation of insulin receptor gene expression. Hydrocortisone and insulin act by different mechanisms. J. Biol. Chem. 263: 13185, 1988.PubMedGoogle Scholar
  22. 22.
    Levy J.R., Hug V. Regulation of insulin receptor gene expression. Cell cycle-mediated effects on insulin receptor mRNA stability. J. Biol. Chem. 267: 25289, 1992.PubMedGoogle Scholar
  23. 23.
    Tewari M., Tewari D.S., Taub R. Posttranscriptional mechanisms account for differences in steady state levels of insulin receptor messenger RNA in different cells. Mol. Endocrinol. 5: 656, 1991.CrossRefGoogle Scholar
  24. 24.
    Lee J-K.,Tsai S.Y. Multiple hormone response elements can confer glucocorticoid regulation on the human insulin receptor gene. Mol. Endocrinol. 8: 625, 1994.PubMedGoogle Scholar
  25. 25.
    Rius C., Aller P. Modulation of ornithine decarboxylase gene transcript levels by differentiation induced in human promyelocytic leukemia HI-60 cells. Cell Differ. Dev. 28: 39, 1989.PubMedCrossRefGoogle Scholar
  26. 26.
    Rouis M., Thomopoulos P., Louache F., Testa U., Hervy C., Titeux M. Differentiation of U-937 human monocyte-like cell line by 1,25-Dihydroxyvitamin D3 or by retinoic acid. Opposite effects on insulin receptors. Exp. Cell Res. 157: 539, 1985.PubMedCrossRefGoogle Scholar
  27. 27.
    Leal M.A., Aller P., Mas A., Calle C. The effect of 1,25-Dihydroxyvitamin D3 on insulin binding, insulin receptor mRNA levels and isotype RNA pattern in U-937 human promonocytic cells. Exp. Cell Res. 217: 189, 1995.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1996

Authors and Affiliations

  • M. A. Leal
    • 1
  • P. Aller
    • 2
  • C. Calle
    • 1
  1. 1.Departamento de Bioquímica, Facultad de MedicinaUniversidad ComplutenseMadridSpain
  2. 2.Centro de Investigaciónes BiológicasC.S.I.C.MadridSpain

Personalised recommendations