Genomic and proteomic approaches for probing the role of vitamin D in health.

Abstract

Although we have learned a great deal about vitamin D metabolism and function since it first became apparent that this factor was required for bone health, there are still many gaps in our understanding, at both the basic science (eg, the molecular actions and targets of vitamin D) and applied (eg, what "adequate" vitamin D status means) levels. For example, although the identification of extrarenal 1alpha-hydroxylase activity suggests that autocrine/paracrine actions of 1,25-dihydroxyvitamin D complement the classic endocrine actions of the hormone, the practical implications of this finding are only now being explored. In addition, studies showed that 1,25-dihydroxyvitamin D rapidly activates signal transduction pathways in addition to the classic transcriptional activation pathways that require the vitamin D receptor. These new modes of vitamin D action may be crucial to our understanding of both the traditional calcium-regulating actions of vitamin D and the anticancer actions of this essential mediator. Recent developments in genomics and proteomics have provided new opportunities for us to identify molecular targets of vitamin D action. Cancer researchers have demonstrated that these methods have utility for identifying useful biomarkers of disease states. Can these approaches be used to help clarify what constitutes optimal serum concentrations of 25-hydroxyvitamin D? I present an overview of how proteomic and genomic evaluations of cells, animals, and human subjects have been and can be used to improve our understanding of vitamin D biological processes and the role of vitamin D in health.