Fibroblast growth factor 23

The main function of FGF23 seems to be regulation of phosphate concentration in plasma. FGF23 is secreted by osteocytes in response to decreased calcitriol. FGF23 acts on the kidneys, where it decreases the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule.[7] Thus, FGF23 decreases the reabsorption of calcium and increases excretion of phosphate. [8]

FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption.[6][9]

FGF23 is located on chromosome 12 and is composed of three exons. Mutations in FGF23 that render the protein resistant to proteolytic cleavage leads to increased activity of FGF23 and the renal phosphate loss found in the human disease autosomal dominant hypophosphatemic rickets. FGF23 is also overproduced by some types of tumors, such as the benign mesenchymal neoplasm Phosphaturic mesenchymal tumor causing tumor-induced osteomalacia, a paraneoplastic syndrome.[10][11]

Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis. This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets.[12] Mice lacking either FGF23 or the klotho enzyme display premature aging due to hyperphosphatemia.[13]

Prior to its discovery in 2000, it was hypothesized that a protein existed which performed the functions subsequently shown for FGF23. This putative protein was known as phosphatonin.[14] Several types of effects were described including impairment of sodium dependent phosphate transport in both intestinal and renal brush border membrane vesicles, inhibition of production of calcitriol, stimulation of breakdown of calcitriol, and inhibition of production/secretion of parathyroid hormone.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.