1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells.
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)
Neveu
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I
Institut National de la Santé et de la Recherche Médicale, Unité U.298, Centre Hospitalier Régional et Universitaire, Angers, France.
Naveilhan
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P
Jehan
F
F
Baudet
C
C
Wion
D
D
De Luca
H F
HF
Brachet
P
P
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D005910:Glioma; D007700:Kinetics; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D018167:Receptors, Calcitriol / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol