Research carried out over the last 10 years has supported a wider role for vitamin D in human health, with proposed beneficial effects for cancer, inflammation and infection and cardiovascular disease. A key component of this new perspective on vitamin D is the increased risk of common human diseases associated with decreased circulating levels of 25-hydroxyvitamin D (25D), more commonly referred to as vitamin D-deficiency. Although 25D is the major serum form of vitamin D, it is an inactive precursor of hormonal 1,25-dihydroxyvitamin D (1,25D). There is therefore a broad assumption that 25D is converted to 1,25D in a tissue-specific manner via localised expression of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1). Expression of CYP27B1 has been described for many tissues, but this intracrine model is nevertheless dependent on another key facet of vitamin D physiology, namely the delivery of substrate 25D to the appropriate cells. In serum 25D circulates predominantly by binding to vitamin D binding protein (DBP), which has a higher affinity for 25D than 1,25D. DBP is therefore a key factor in mediating many of the actions of vitamin D, but it is still unclear whether DBP plays an active role in the delivery of 25D to CYP27B1-expressing cells. The membrane receptor for DBP, megalin, is widely expressed but is not detectable in many key target cells for vitamin D, notably cells from the immune system. Thus in some settings, it appears that unbound or free 25D is the form of vitamin D that is able to access cells, even though this fraction of circulating vitamin D is very small. The aim of this presentation is to explore the importance of bound versus free 25D in defining the different actions of vitamin D, and the implications this may have for the analysis and clinical application of vitamin D.
07 Nov 2016 - 09 Nov 2016