1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells

Brain Res Mol Brain Res. 1994 Jul;24(1-4):70-6. doi: 10.1016/0169-328x(94)90119-8.

Abstract

The effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3) on nerve growth factor (NGF) synthesis was investigated in primary cultures of astrocytes prepared from brain of neonatal rats. 1,25-(OH)2 D3 elicited a dose-dependent increase of NGF mRNA with a maximal effect at 10(-7) M, which persisted for at least 48 h. Northern blot analysis revealed an expression of the vitamin D3 receptor (VDR) gene in primary glial cells. Treatment of cells with 1,25-(OH)2 D3 led to an increase in the VDR mRNA levels. Similar results were obtained in C6 glioma cells. Exposure of primary glial cells to 10(-8) M 1,25-(OH)2 D3 caused only a 2-fold increase of the levels of cell-secreted NGF after 3 days of treatment. However, a 5-fold increase was observed three days after a second addition of vitamin D3. Likewise, a pretreatment with lower doses of hormone such as 10(-10) M or 10(-9) M enhanced the responsiveness of the cells to a 24 h treatment with 10(-8) M hormone. It appears, therefore, that the duration of the treatment influences the level of synthesis of NGF, possibly as a consequence of the increase of the VDR gene expression. The specificity of 1,25-(OH)2 D3 is supported by the fact that a concentration of 10(-7) M of an another vitamin D3 metabolite, 24,25-(OH)2 D3, had no effect on NGF synthesis. Several lines of evidence indicate that astrocytes constitute the major cell type responsive to 1,25-(OH)2 D3 in primary cultures of glial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • 24,25-Dihydroxyvitamin D 3 / pharmacology
  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Blotting, Northern
  • Brain / metabolism*
  • Calcitriol / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects*
  • Glioma
  • Kinetics
  • Nerve Growth Factors / biosynthesis*
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Receptors, Calcitriol / biosynthesis
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Nerve Growth Factors
  • RNA, Messenger
  • Receptors, Calcitriol
  • 24,25-Dihydroxyvitamin D 3
  • Calcitriol