[Understanding the different functions of vitamin D]

Exposure of the skin to sunlight is now considered the most important source of vitamin D in Western countries. It is presumed to contribute approximately two thirds of the total requirement, leaving the remaining one third to the few foods naturally rich in this vitamin. In the skin, vitamin D is synthesized as a cholesterol chain which undergoes structural modifications following exposure to UVB rays. Once produced in the skin or absorbed in the gut as cholecalciferol, vitamin D enters the blood to be transported by a specific vitamin D binding protein, which is synthesized in the liver and has a powerful buffering capacity. The transport system carries the metabolites to the sites of further activation (25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney), ultimately resulting in the production of calcitriol. This last compound, now regarded as a hormone, circulates freely in minimal amounts and, compared with the other metabolites, shows the highest affinity for the vitamin D receptor (VDR). The mechanism of VDR activation is rather complex, resulting in either stimulation or inhibition of protein synthesis. Importantly, besides its presence in parathyroid, bone, kidney and intestine, this receptor has been demonstrated in several tissues, where its stimulation results in a reduced proliferation rate and increased differentiation. Accordingly, vitamin D is now regarded as a complex hormonal system, involved not only in the regulation of divalent ions and bone, but also in the proliferation and differentiation of numerous cell types with potential involvement in several diseases like cancer, immune diseases, diabetes, hypertension and heart failure.