Molecular and Cellular Biochemistry

, Volume 124, Issue 1, pp 23–32 | Cite as

Relevance of c-fos proto-oncogene induction for the steroidogenic response to ACTH, dcAMP and phorbol ester in adrenocortical cells

  • Eico Kimura
  • Claudi K. Frigeri
  • Hugo A. Armelin
Article
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Accepted:

Abstract

We previously reported that ACTH, but not dibutyryl cAMP, rapidly induces the c-fos proto-oncogene in Y-1 adrenocortical cells.

Here we show that PMA induces c-fos with similar kinetics when compared with ACTH (0.5–1 h peak) but reaches only 60% of the maximal ACTH induction and dcAMP is a weak c-fos inducer (15% of ACTH). However, combination of PMA and dcAMP has a synergistic effect leading to maximal c-fos induction. c-fos expression may play a role in the RNA synthesis-dependent corticosteroidogenesis response and/or growth regulation by ACTH.

We also show that, in contrast to dcAMP, PMA is a poor steroidogenesis stimulator (15 to 17% of maximum ACTH-stimulated level), its activity being completely dependent on RNA synthesis. Combination of dcAMP and PMA yields an additive steroidogenesis stimulation, an effect that is also dependent on RNA synthesis. Although no strict correlation was found between c-fos induction and early steroidogenesis stimulation, particularly with respect to cAMP derivatives, the results suggest that a PKC pathway is likely to cooperate with the classical cAMP-PKA pathway in adrenal cells' RNA-dependent steroidogenesis.

Key words

ACTH phorbol ester dibutyryl cAMP adrenocortical cells steroidogenic response c-fos proto-oncogene induction 

Abbreviations

ACTH

Adrenocorticotropic Hormone

PMA

Phorbol-12-Myrystate-13-Acetate

dcAMP

dibutyryl cyclic AMP

DME

Dulbecco's Modified Eagle's minimal medium

FCS

Fetal Calf Serum

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References

  1. 1.
    Schimmer BP: The adrenocortical tumor cell line, Y-1. In: Sato G (ed) Functionally Differentiated Cell Lines, Liss, New York, 1981, pp 61–92Google Scholar
  2. 2.
    Kimura E, Armelin HA: c-fos induction accompanies cell cycle block by ACTH. J Cell Biochem Supplement 12A: 220, 1988Google Scholar
  3. 3.
    Kimura E, Armelin HA: Phorbol ester mimics ACTH action in corticoadrenal cells stimulating steroidogenesis, blocking cell cycle, changing cell shape and inducing c-fos proto-oncogene expression. J Biol Chem 265: 3518–3521, 1990PubMedGoogle Scholar
  4. 4.
    Imai T, Seo H, Murata Y, Ohno M, Satoh, Y, Funahashi H, Takagi H, Matsui N: Adrenocorticotropin increases expression of c-fos and beta-actin genes in the rat adrenals. Endocrinology 127: 1742–1747 1990PubMedGoogle Scholar
  5. 5.
    Yang G, Koistinaho J, Iadarola M, Zhu SH, Hervonen A: Administration of adrenocorticotropic hormone (ACTH) enhances Fos expression in the rat adrenal cortex. Regul Pept 30: 21–31, 1990PubMedGoogle Scholar
  6. 6.
    Curran T, Franza Jr BR: Fos and Jun: the AP-1 connection. Cell 55: 345–397, 1988Google Scholar
  7. 7.
    Moyle WR, Kong C, Ramachandran J: Steroidogenesis and cyclic adenosine 3′, 5′-monophosphate accumulation in rat adrenal cells. J Biol Chem 248: 2409–2417, 1973PubMedGoogle Scholar
  8. 8.
    Rae PA, Gutmann NS, Tsao J, Schimmer BP: Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis. Proc Natl Acad Sci USA 76: 1896–1900, 1979PubMedGoogle Scholar
  9. 9.
    Farese RV, Rosic N, Babischkin J, Farese MG, Foster R, Davis JS: Dual activation of the inositol-triphosphate-calcium and cyclic nucleotide intracellular signaling systems by adrenocorticotropin in rat adrenal cells. Biochem Biophys Res Commun 135: 742–748, 1986PubMedGoogle Scholar
  10. 10.
    Farese RV, Fanjul LF, de Ruiz Gallareta CM, Davis JS, Cooper DR: ACTH increases diacylglycerol content and subcellular redistribution of protein kinase C in the rat adrenal ‘in vivo”. Life Sci 41: 2631–2637, 1987PubMedGoogle Scholar
  11. 11.
    Estensen R, Zustiak K, Chuang A, Schultherss P, Ditmanson J: Action of TPA on Y-1 adrenal cells apparently requires the regulatory subunit of type 1 c-AMP-dependent protein kinase. J Exp Pathol 1: 49–60, 1983PubMedGoogle Scholar
  12. 12.
    Widmaier EP, Hall PF: Protein kinase C in adrenal cells: possible role in regulation of steroid synthesis. Mol Cell Endocrinol 43: 181–188, 1985PubMedGoogle Scholar
  13. 13.
    Garren LD, Gill GN, Masui H, Walton GM: On the mechanism of action of ACTH. Recent Progr Horm Res 27: 433–478, 1971PubMedGoogle Scholar
  14. 14.
    Yasumura Y, Buonassissi Y, Sato G: Clonal analysis of differentiated function in animal cell cultures. I. Possible correlated maintenance of differentiated function and the diploid karyotype. Cancer Res 26: 529–535, 1966PubMedGoogle Scholar
  15. 15.
    George D, Francke U: Homogeneously staining chromosome regions and double minutes in a mouse adrenocortical tumor cell line. Cytogenet Cell Genet 28: 217–226, 1980PubMedGoogle Scholar
  16. 16.
    Chirgwin J, Przybyla AE, McDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294–5299, 1979PubMedGoogle Scholar
  17. 17.
    Ellis RW, De Feo D, Shih TY, Gonda MA, Young HA, Tsuchida N, Lowy D, Scolnick EM: The p21 src genes of Harveyand Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature 292: 506–511, 1981PubMedGoogle Scholar
  18. 18.
    Curran T, Peters G, Van Beveren C, Teich NM, Verma IM: FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol 44: 674–682, 1982PubMedGoogle Scholar
  19. 19.
    Piechazyk M, Blanchard JM, Marty L, Dani Ch, Panabieres F, El Sabouty S, Fort Ph, Janteur Ph: Post-transcriptional, regulation of glyceraldeide-3-phosphate-dehydrogenase gene expression in rat tissues. Nucl Acids Res 12: 6951–6963, 1984PubMedGoogle Scholar
  20. 20.
    Feinberg A, Vogelstein B: A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Addendum Anal Biochem 137: 266–267, 1984Google Scholar
  21. 21.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275, 1951PubMedGoogle Scholar
  22. 22.
    Nishizuka Y: The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308: 693–698, 1984PubMedGoogle Scholar
  23. 23.
    Garren LD, Ney RL, Davis WW Studies on the role of protein synthesis in the regulation of corticosterone production by adrenocorticotropic hormonein vivo. Proc Natl Acad Sci USA, 53: 1443–1450, 1965PubMedGoogle Scholar
  24. 24.
    Miyamoto N, Seo H, Kanda K, Hidaka H, Matsui N: A cAMP-dependent pathway is responsible for a rapid increase in c-fos mRNA by ACTH. Endocrinology 130: 3231–3236, 1992PubMedGoogle Scholar
  25. 25.
    Viard I, Hall SH, Jaillard C, Berthelon MC, Saez JM: Regulation of c-fos, c-jun and jun B mRNA by Angiotensin-II and corticotropin in ovine and bovine adrenocortical cells. Endocrinology 130: 1193–1200, 1992PubMedGoogle Scholar
  26. 26.
    Schwab M, Alitalo K, Varmus HE, Bishop JM, George D: Acellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumor cells. Nature 303: 497–501, 1983PubMedGoogle Scholar
  27. 27.
    Kimura E, Armelin HA: Role of proto-oncogene c-Ki-ras amplification and overexpression in the malignancy of Y-1 adrenocortical tumor cells. Brazilian J Med Biol Res 21: 189–210, 1988Google Scholar
  28. 28.
    Simpson ER, Waterman MR: Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH. Ann Rev Physiol 50: 427–440, 1988Google Scholar
  29. 29.
    Moore CCD, Miller WL: The role of transcriptional regulation in steroid hormone biosynthesis. J Steroid Biochem Molec Biol 40: 517–525, 1991PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • Eico Kimura
    • 1
  • Claudi K. Frigeri
    • 1
  • Hugo A. Armelin
    • 1
  1. 1.Department of Biochemistry, Institute of ChemistryUniversity of Sao PauloSao PauloBrazil

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