1,25-dihydroxyvitamin D-3 regulates the expression of the low-affinity neurotrophin receptor

1,25-Dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) is known to regulate the expression of neurotrophins [45,46]. Here, we report that 1,25-(OH)(2)D-3 does not influence the expression of truncated or full-length forms of trkB and trkC receptors mRNAs in primary cultures of astrocytes and in C6 glioma cells. In contrast, low concentrations of 1,25-(OH)(2)D-3 increased low-affinity neurotrophin receptor (P75(NTR)) mRNA and protein levels in C6 glioma cells. Putative vitamin D responsive elements (VDRE) in the P75(NTR) promoter have - 610 and - 860 bp upstream from the translation start codon was found to respond to 1,25-(OH)(2)D-3. Interestingly, 1,25-(OH)(2)D-3 does not regulate p75(NTR) in primary cultures of astrocytes even at concentration as high as 10(-7) M. Since long-term treatment of 1,25-(OH)(2)D-3 induces cell death in C6 glioma cells but not in primary astrocytes [41], the possible involvement of P75(NTR) in 1,25-(OH)(2)D-3-induced cell death is discussed. Finally, in-vivo studies show that treatment of 15-day-old and adult rats with 1,25-(OH)(2)D-3 leads to a decrease in the level of P75(NTR) mRNA in the spinal cord but does not influence its expression in dorsal root ganglion or sciatic nerve. These results suggest that 1,25-(OH)(2)D-3 may have a role in the specific regulation of P75(NTR) in vivo.