Figure 1.

Sources, metabolism and cellular mode of action of VitD. VitD is synthesized in the skin under the effect of UV radiation and is also provided by food sources. Cholecalciferol (inactive form) is stored in adipose tissue and transformed in the liver into 25-hydroxyvitamin D₃ [25(OH)D₃, calcidiol—main circulating form]. Calcidiol is then hydroxylated in the kidney to form 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃, calcitriol—active metabolite]. VitD metabolites circulate ubiquitously, bound to its transporter: Vit DBP and is able to cross the blood–brain barrier to modulate CNS-resident cells (neurons, astrocytes, oligodendrocytes and microglia). Calcitriol acts intracellularly as a transcription factor by binding to the cytoplasmic VDR which heterodimerizes with RXR. Upon translocation of this heterodimer to the nucleus, VitD/VDR/RXR complex binds to the VDRE in the genomic DNA and modulates the expression of target genes. Drawings of the individual cell types were adapted from Servier Medical Art (http://smart.servier.com/), licenced under a Creative Common Attribution 3.0 Generic License.