Fibroblast growth factor 23

Function

The main function of FGF23 seems to be regulation of phosphate concentration in plasma. FGF23 is secreted by osteocytes in response to elevated calcitriol. FGF23 acts on the kidneys, where it decreases the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule. Thus, FGF23 decreases the reabsorption and increases excretion of phosphate. FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption.

Clinical significance

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. 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. Prior to discovery in 2000, it was hypothesized that a protein existed which performed the function of FGF23. This putative protein was known as phosphatonin.Two major types of effects • Direct Effects: • 1. Impairs sodium dependent phosphate transport in both intestinal and renal brush border membrane vesicles • 2. Inhibits production of calcitriol and stimulates breakdown of calcitriol • 3. Inhibits production/secretion of parathyroid