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 e xpression 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 an d in C6 glioma cells. In contrast, low concentrations of 1,25-(OH)(2)D -3 increased low-affinity neurotrophin receptor (P75(NTR)) mRNA and pr otein levels in C6 glioma cells. Putative vitamin D responsive element s (VDRE) in the P75(NTR) promoter have - 610 and - 860 bp upstream fro m 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. Sinc e long-term treatment of 1,25-(OH)(2)D-3 induces cell death in C6 glio ma 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. Finall y, in-vivo studies show that treatment of 15-day-old and adult rats wi th 1,25-(OH)(2)D-3 leads to a decrease in the level of P75(NTR) mRNA i n 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.