Vitamin D metabolites; protective versus toxic properties: molecular and cellular perspectives

Vitamin D plays an essential role in bone metabolism. The discovery that the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, is expressed in most tissues led researchers to investigate other biological actions of vitamin D. These effects were found to include anti-inflammatory effects and anti-atherogenesis, decreased renin activity and biosynthesis, induction of cell differentiation, inhibition of cell growth, and immunomodulation. In spite of the plethora of evidence on the protective effects of vitamin D, the reports on its intoxication still are considerably few. Therefore, in this review we aim to summarize the molecular and cellular bases of the protect-ive and toxic vitamin D actions that are mediated mostly by VDR. This review will also shed light on vitamin D metabolites other than the active metabolite calcitriol and particularly 25-hydroxy vitamin D (25(OH)D), putting emphasis on its magnifying role in vitamin D intoxication. One of the important themes we discuss is defining serum levels of beneficial or toxic effects of other exogenous vitamin D administration and its impact on 25(OH)D serum levels in animals and human subjects.