Figure 1.

A, Summary of distinctions between the two, phylogentically discrete functions of vitamin D (see Footnote 1), one as a circulating hormone (left) and the other as a locally produced, locally active cytokine made by monocyte-macrophages (right). B, Schematic tracing the serial endocrine responses to a diminishment in vitamin D-directed intestinal calcium absorption as might be seen in humans with acquired vitamin D insufficiency/deficiency; the final step in the process is 1,25-dihydroxyvitamin D (1,25-D) stimulation of genes controlling calcium absorption from the gut, mobilization of calcium from the skeleton and, finally, synthesis and release of FGF23, which acts to return previously enhanced PTH and CYP27B1-hydroxylase gene expression to normal. DBP, Vitamin D binding protein; RXR, retinoid X receptor.