Recent insights into vitamin D and its receptor.

The widely differing functions of vitamin D are based both on a wide diffusion of its specific receptor (VDR) and on the ability of many cells, in addition to renal tubular cells, to synthesize calcitriol for autocrine and paracrine functions. In the last few years, many published studies have added new insights into some important points on this topic. Recent data suggest that the control of calcitriol synthesis at tissue levels other than kidneys might differ greatly from the control system working at the renal level. Furthermore, the mechanisms by which the VDR might mediate either the genomic and nongenomic (rapid) vitamin D-mediated effects became much clearer. However, new evidence accumulated suggests that some additional receptor(s), responsive to vitamin D and different from the VDR, could play a role in the rapid response to vitamin D, probably interfering also with the genomic pathway. In this context, there are new possible interpretations of the mechanisms by which different vitamin D metabolites might express variable activities at different levels. In addition, some recent data have challenged the role of the VDR in direct parathyroid hormone (PTH) control, at least in physiological conditions, suggesting that vitamin D-mediated PTH inhibition is mainly secondary to the intestinal effect on calcium absorption. Finally, there is a renewed interest in the field of polymorphic variants in the VDR gene in relation to some clinical conditions, though the mechanisms underlining these associations are far from being clear. The present review briefly addresses all of the above points.