Skip to main content
SpringerLink
Log in

Corticosteroids regulate the gene expression of FGF-1 and FGF-2 in cultured rat astrocytes

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The present data show that the gene expression of FGF-1 and FGF-2 is regulated by corticosteroids in rat type 1 astrocytes. In particular, the gene expression of FGF-1 is modulated by corticosteroids acting both on type I (minerocorticoid) and type II (glucocorticoid) receptors. In fact, at short times of exposure (2 h) a slight decrease in FGF-1 mRNA levels is induced by deoxycorticosterone, a steroid able to interact with the type I receptors; a similar effect is observed at 6 h following exposure to corticosterone or its 5α-reduced metabolite, dihydrocorticosterone. Conversely, at longer times of exposure (24 h) corticosterone is able to strongly increase FGF-1 mRNA levels. Both effects of corticosterone (inhibition and stimulation) were duplicated by dexamethasone, indicating that both effects occur via the type II receptors. Interestingly, the 5α-3α-reduced metabolite of deoxycorticosterone, tetrahydrodeoxycorticosterone, which does not interact with either corticosteroid receptors, is able to stimulate (at 6 and 24 h of exposure) the gene expression of FGF-1. It is possible that this effect might be induced via the GABAA receptor, since muscimol, an agonist of this receptor, exerts a similar effect.

The situation is different in the case of FGF-2. The mRNA levels of this growth factor are only stimulated by steroids interacting with type II receptors. Altogether, these observations indicate that corticosteroids modulate the levels of FGF-1 and FGF-2 gene expression in astroglial cells by interaction with classical (type I and II) or nonclassical (GABAA receptor) steroid receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baird A. (1994) Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors. Curr. Opinion Neurobiol. 4, 78–86.

    Article  CAS  Google Scholar 

  • Bikfalvi A., Klein S., Pintucci G. and Rifkin D. B. (1997) Biological roles of fibroblast growth factor-2. Endocrine Rev. 18, 26–45.

    Article  CAS  Google Scholar 

  • Bohn M. C., O’Banion M. K., Young D. A., Giuliano R., Hussain S., Dean D. A. and Cunningham L. A. (1994) In vitro studies of glucocorticoid effects on neurons and astrocytes. Ann. NY Acad. Sci. 746, 243–259.

    Article  PubMed  CAS  Google Scholar 

  • Bovolin P., Santi M. R., Puia G., Costa E. and Grayson D. (1992) Expression patterns of y-aminobutyric acid type A receptor subunit mRNAs in primary cultures of granule neurons and astrocytes from neonatal rat cerebella. Proc. Natl. Acad. Sci. USA 89, 9344–9348.

    Article  PubMed  CAS  Google Scholar 

  • Bugra K., Pollard H., Charton G., Moreau J., Ben-Ari Y., and Khrestchatisky M. (1994) aFGF, bFGF and flg mRNAs show distinct patterns of induction in the hippocampus following kainate-induced seizures. Eur. J. Neurosci. 6, 58–66.

    Article  PubMed  CAS  Google Scholar 

  • Celotti F., Melcangi R. C. and Martini L. (1992) The 5α-reductase in the brain: molecular aspects and relation to brain function. Front. Neuroendocrinol. 13, 163–215.

    PubMed  CAS  Google Scholar 

  • Chomczynski P. and Sacchi N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159.

    Article  PubMed  CAS  Google Scholar 

  • Chou Y. C., Luttge W. G. and Sumners C. (1991) Expression of mineralocorticoid type I and glucocorticoid type II receptors in astrocyte glia as a function of time in culture. Dev. Brain Res. 61, 55–61.

    Article  CAS  Google Scholar 

  • Hosli E., Otten U. and Hosli L. (1997) Expression of GABAA receptors by reactive astrocytes in explant and primary cultures of rat CNS. Int. Devel. Neurosc. 15, 949–960.

    Article  CAS  Google Scholar 

  • Joels M. (1997) Steroid hormones and excitability in the mammalian brain. Frontiers Neuroendocrinol. 18, 2–48.

    Article  CAS  Google Scholar 

  • Joels M. and Vreugdenhil E. (1998) Corticosteroids in the brain. Cellular and molecular actions. Mol. Neurobiol. 17, 87–108.

    PubMed  CAS  Google Scholar 

  • Logan A., Oliver J. J. and Berry M. (1994) Growth factors in CNS repair and regeneration. Progr. Growth Factor Res. 5, 379–405.

    Article  CAS  Google Scholar 

  • McEwen B. S. and Gould E. (1990) Adrenal steroid influences on the survival of hippocampal neurons. Biochem. Pharmacol. 40, 2393–2402.

    Article  PubMed  CAS  Google Scholar 

  • Melcangi R. C., Celotti F., Ballabio M., Castano P., Massarelli R., Poletti A. and Martini L. (1990) 5α-Reductase activity in isolated and cultured neuronal and glial cells of the rat. Brain Res. 516, 229–236.

    Article  PubMed  CAS  Google Scholar 

  • Melcangi R. C., Celotti F., Castano P. and Martini L. (1993) Differential localization of the 5α-reductase and the 3α-hydroxysteroid dehydrogenase in neuronal and glial cultures. Endocrinology 32, 1252–1259.

    Article  Google Scholar 

  • Melcangi R. C., Magnaghi V., Cavarretta I., Riva M. A., Piva F. and Martini L. (1998a) Effects of steroid hormones on gene expression of glial markers in the central and peripheral nervous system: variations induced by aging. Exp. Gerontol. 33, 827–836.

    Article  PubMed  CAS  Google Scholar 

  • Melcangi R. C., Poletti A., Cavarretta I., Celotti F., Colciago A., Magnaghi V., Motta M., Negri-Cesi P. and Martini L. (1998b) The 5α-reductase in the central nervous system: expression and modes of control. J. Steroid Biochem. Mol. Biol. 65, 295–299.

    Article  PubMed  CAS  Google Scholar 

  • Melcangi R C., Magnaghi V. and Martini L. (1999) Steroid metabolism and effects in central and peripheral glial cells. J. Neurobiol. 40, 471–483.

    Article  PubMed  CAS  Google Scholar 

  • Poulter M. O. and Brown L. A. (1999) Transient expression of GABAA receptor subunit mRNAs in the cellular processes of cultured cortical neurons and glia. Mol. Brain Res. 69, 44–52.

    Article  PubMed  CAS  Google Scholar 

  • Riva M. A., Gale K. and Mocchetti I. (1992) Basic fibroblast growth factor mRNA increases in specific brain regions following convulsive seizures. Mol. Brain Res. 15, 311–318.

    Article  PubMed  CAS  Google Scholar 

  • Riva M. A., Donati E., Tascedda F., Zolli M. and Racagni G. (1994) Short- and long-term induction of basic fibroblast growth factor gene expression in rat central nervous system following kainate injection. Neuroscience 59, 55–65.

    Article  PubMed  CAS  Google Scholar 

  • Riva M. A., Fumagalli F., Blom J. M. C., Donati E. and Racagni G. (1995a) Adrenalectomy reduces FGF-1 and FGF-2 gene expression in specific rat brain regions and differently affects their induction by seizures. Mol. Brain Res. 34, 190–196.

    Article  PubMed  CAS  Google Scholar 

  • Riva M. A., Fumagalli F. and Racagni G. (1995b) Opposite regulation of basic fibroblast growth factor and nerve growth factor gene expression in rat cortical astrocytes. J. Neurochem. 64, 2526–2533.

    Article  PubMed  CAS  Google Scholar 

  • Riva M. A., Molteni R., Lovati E., Fumagalli F., Rusnati M. and Racagni G. (1996) Cyclic AMP-dependent regulation of fibroblast growth factor-2 messenger RNA levels in rat cortical astrocytes: comparison with fibroblast growth factor-1 and ciliary neurotrophic factor. Mol. Pharmacol. 49, 699–706.

    PubMed  CAS  Google Scholar 

  • Rowntree S. and Kolb B. (1997) Blockade of basic fibroblast growth factor retards recovery from motor cortex injury in rats. Eur. J. Neurosci. 9, 2432–2442.

    Article  PubMed  CAS  Google Scholar 

  • Rupprecht R., Hauser C. A. E., Trapp T., and Holsboer F. (1996) Neurosteroids: molecular mechanisms of action and psychopharmacological significance. J. Steroid Biochem. Mol. Biol. 56, 163–168.

    Article  PubMed  CAS  Google Scholar 

  • Sapolsky R. M., Krey L., and McEwen B. (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J. Neurosci. 5, 1221–1227.

    Google Scholar 

  • Scully J. L. and Otten U. (1995) Glucocorticoids, neurotrophins and neurodegeneration. J. Steroid Biochem. 52, 391–401.

    Article  CAS  Google Scholar 

  • Solviter R. S., Valiquette G., Abrams G. M., Ronk E. C., Sollas A. L., Paul L. A. and Neubort S. (1989) Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science 243, 535–538.

    Article  Google Scholar 

  • Vaccarino F. M., Schwartz M. L., Raballo R., Nilsen J., Rhee J., Zhou M., Doetschman T., Coffin J. D., Wyland J. J. and Huang Y.-T. E. (1999) Changes in cerebral cortex size are governed by FGF during embyogenesis. Nature Neurosci. 2, 246–253.

    Article  PubMed  CAS  Google Scholar 

  • Vielkind U., Walencewicz A., Levine J. M., and Bohn M. C. (1990) Type II glucocorticoid receptors are expressed in oligodendrocytes and astrocytes. J. Neurosci. Res. 27, 360–373.

    Article  PubMed  CAS  Google Scholar 

  • Wooley C. S., Gould E., Sakai R. R., Spencer R. L. and McEwen B. S. (1991) Effects of aldosterone or RU28362 treatment on adrenalectomy-induced cell death in the dentate gyrus of the adult rat. Brain Res. 554, 312–315.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, University of Milan, Via G. Balzaretti 9, 20133, Milan, Italy

    V. Magnaghi, I. Cavarretta, L. Martini & R. C. Melcangi

  2. Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan Via G. Balzaretti 9, 20133, Milan, Italy

    M. A. Riva

Authors
  1. V. Magnaghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. A. Riva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Cavarretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. C. Melcangi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. C. Melcangi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magnaghi, V., Riva, M.A., Cavarretta, I. et al. Corticosteroids regulate the gene expression of FGF-1 and FGF-2 in cultured rat astrocytes. J Mol Neurosci 15, 11–18 (2000). https://doi.org/10.1385/JMN:15:1:11

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:15:1:11

Key Words

Search

Navigation