Autocrine and paracrine actions of vitamin d.

Vitamin D deficiency continues to attract considerable attention because of claims that an adequate status can reduce the risk of a wide range of diseases. The facts are that this hormone modulates the expression of a very large number of genes, possibly some 5 to 10% of the genome; that it has been subject to very strong evolutionary pressures; and that its biological activities are exerted across a wide range of tissues, and these all contribute to the plausibility that such claims may eventually be found to be valid. While the endocrine action of the active metabolite, 1,25-dihydroxyvitamin D, has been well-characterised to contribute to maintaining plasma calcium and phosphate homeostasis through regulation of intestinal absorption, recent research has focused on its autocrine and/or paracrine activities. Such activities of vitamin D have been best characterised in skin tissues and the immune system where it regulates cell differentiation and maturation as well as the innate immune system. Recent data are now available to implicate autocrine/paracrine activities in each of the major bone cell types where it also regulates cell proliferation and differentiation. In rodent models, adequate levels of serum 25-hydroxyvitamin D have been found to be critical to optimise bone health and to protect against osteoporosis. These findings are consistent with clinical data that such activity is present in humans. The introduction of an autocrine/paracrine paradigm for vitamin D has significant implications for critical levels of serum 25-hydroxyvitamin D for optimal health.