Figure 2

Actions of FGF23. FGF23 is produced by bone. FGF23 suppresses the expression of type 2a and 2c sodium-phosphate cotransporters (NaPi) in the brush border membrane of proximal tubules which mediate physiological phosphate reabsorption. In addition, FGF23 reduces serum 1,25(OH)₂D level by suppressing the expression of 25-hydroxyvitamin D [25(OH)D]-1α-hydroxylase and also enhancing the expression of 25(OH)D-24-hydroxylase. This 1α-hydroxylase mediates the production of 1,25(OH)₂D from 25(OH)D, and 24-hydroxylase converts 1,25(OH)₂D into more hydrophilic metabolites with less activity. Because 1,25(OH)₂D enhances intestinal phosphate absorption, FGF23 reduces serum phosphate level by its suppressive effects on renal phosphate reabsorption and intestinal phosphate absorption. Conversely, 1,25(OH)₂D increases FGF23 level. High phosphate diet also increases circulatory FGF23. However, it remains to be clarified how changes in dietary phosphate modulate FGF23 level.