Trichostatin A stimulates steroid 5alpha-reductase gene expression in rat C6 glioma cells via a mechanism involving Sp1 and Sp3 transcription factors

J Mol Neurosci. 2010 Jun;41(2):252-62. doi: 10.1007/s12031-009-9284-6. Epub 2009 Sep 2.


The adrenergic and serotonergic stimulations of rat C6 glioma cells have previously been shown to induce the activation of steroid 5alpha-reductase (5alpha-R) gene expression, resulting in their differentiation through the production of neuroactive 5alpha-reduced steroid metabolites. In addition, progesterone and histone deacetylase (HDAC) inhibitors have also been reported to promote the glial cell differentiation with the enhancement of serotonin-stimulated brain-derived neurotrophic factor gene transcription through the production of 5alpha-reduced neurosteroids, thus suggesting that glial cell differentiation is probably implicated in the protection and survival of neuronal cells in the brain. Therefore, the expression of 5alpha-R gene in glial cells seems physiologically important in maintaining the neural function in the brain, but little is known about the mechanism underlying the regulation of 5alpha-R gene transcription. In the present study, the effect of a HDAC inhibitor trichostatin A (TSA) on 5alpha-R gene transcription in the glioma cells was examined, and TSA was shown to induce the elevation of 5alpha-R mRNA levels through the activation of the 5alpha-R promoter via a mechanism involving Sp1 and Sp3 transcription factors in a time- and concentration-dependent manner. Thus, both Sp1 and Sp3 are considered to play a physiological role in the regulation of 5alpha-R gene expression, and hence the production of 5alpha-reduced neurosteroids in glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase* / genetics
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase* / metabolism
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Gene Deletion
  • Gene Expression / drug effects*
  • Genes, Reporter
  • Glioma / genetics
  • Glioma / metabolism
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism
  • Hydroxamic Acids / pharmacology*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Rats
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Sp3 Transcription Factor / genetics
  • Sp3 Transcription Factor / metabolism*


  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Sp1 Transcription Factor
  • Sp3 Transcription Factor
  • trichostatin A
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • Histone Deacetylases