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.
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 benignmesenchymalneoplasmPhosphaturic 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
^Yamashita T, Yoshioka M, Itoh N (October 2000). "Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain". Biochem. Biophys. Res. Commun. 277 (2): 494–8. doi:10.1006/bbrc.2000.3696. PMID11032749.
^ abPerwad F (2007). "Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro.". Am J Physiol Renal Physiol. 293: F1577–83. doi:10.1152/ajprenal.00463.2006. PMID17699549.
Econs MJ (2000). "Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23". Nat. Genet. 26 (3): 345–8. doi:10.1038/81664. PMID11062477.
White KE, Jonsson KB, Carn G, Hampson G, Spector TD, Mannstadt M, Lorenz-Depiereux B, Miyauchi A, Yang IM, Ljunggren O, Meitinger T, Strom TM, Jüppner H, Econs MJ (2001). "The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting". J. Clin. Endocrinol. Metab. 86 (2): 497–500. doi:10.1210/jc.86.2.497. PMID11157998.
Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC (2001). "FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate". Biochem. Biophys. Res. Commun. 284 (4): 977–81. doi:10.1006/bbrc.2001.5084. PMID11409890.
White KE, Carn G, Lorenz-Depiereux B, Benet-Pages A, Strom TM, Econs MJ (2002). "Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23". Kidney Int. 60 (6): 2079–86. doi:10.1046/j.1523-1755.2001.00064.x. PMID11737582.
Kruse K, Woelfel D, Strom TM, Storm TM (2002). "Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation". Horm. Res. 55 (6): 305–8. doi:10.1159/000050018. PMID11805436.
Yamashita T, Konishi M, Miyake A, Inui K, Itoh N (2002). "Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway". J. Biol. Chem. 277 (31): 28265–70. doi:10.1074/jbc.M202527200. PMID12032146.
Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N (2003). "Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production". J. Biol. Chem. 278 (4): 2206–11. doi:10.1074/jbc.M207872200. PMID12419819.
Bai XY, Miao D, Goltzman D, Karaplis AC (2003). "The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency". J. Biol. Chem. 278 (11): 9843–9. doi:10.1074/jbc.M210490200. PMID12519781.
Larsson T, Zahradnik R, Lavigne J, Ljunggren O, Jüppner H, Jonsson KB (2003). "Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia". Eur. J. Endocrinol. 148 (2): 269–76. doi:10.1530/eje.0.1480269. PMID12590648.