Figure 5. Noncalcemic functions of 1,25(OH)₂ D.

Vitamin D coming from the photoproduction of previtamin D or coming from the diet is converted in the liver to 25(OH)D by the vitamin 25-OHase. 25(OH)D is converted in the kidneys by 1-OHase. 1,25(OH)₂D not only regulates calcium and phosphorus metabolism but can stimulate the pancreas to produce insulin and to downregulate the renal production of renin. 1,25(OH)₂D also interacts with its nuclear receptor (VDR) in a wide variety of tissues and cells and helps maintain normal cell proliferation and differentiation. 25(OH)D can also be converted to 1,25(OH)₂D in a wide variety of cells, including colon, prostate, and breast, for the autocrine production of 1,25(OH)₂D. It is believed that the autocrine production of 1,25(OH)₂D is important for regulating cell growth and maturation, which decreases risk of the cell becoming malignant. 25(OH)D also is metabolized in macrophages by the 1-OHase to produce 1,25(OH)₂D. The expression of the VDR and 1-OHase is upregulated when TLR2/1 is stimulated by LPS. This results in an increase in the expression of the VDR and the 1-OHase. The increase production of 1,25(OH)₂D increases the nuclear expression of cathelicidin (CD) in the macrophage, which is a cationic peptide that causes the destruction of infective agents including M. tuberculosis.