Reshaping the way we view vitamin D signalling and the role of vitamin D in health

Although the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)(2)D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)(2)D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)(2)D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.