FGF23 and the parathyroid glands.
Fibroblast growth factor 23 (FGF23) is a phosphatonin that is secreted by osteocytes and osteoblasts in response to hyperphosphatemia and 1,25-dihydroxyvitamin D (1,25D). It acts on its receptor complex, Klotho-FGFR1c (fibroblast growth factor receptor 1 c-splicing form), in the distal convoluted tubule to repress renal phosphorus reabsorption in the proximal tubule and suppress the renal synthesis of 1,25D. Klotho-FGFR1c is also expressed in the parathyroid glands. FGF23 acts on the receptor complex in the parathyroid glands to decrease parathyroid hormone (PTH) gene expression and PTH secretion through activation of the MAPK pathway. In chronic kidney disease (CKD), both FGF23 and PTH are increased, implying resistance of the parathyroid glands to FGF23. There is a decrease in the Klotho-FGFR1c complex in the parathyroid glands in both experimental CKD and in patients with end-stage renal disease. In addition, in advanced experimental CKD, FGF23 has a decreased ability to inhibit PTH expression.
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, 91120, Israel. silver@huji.ac.il
Justin
J
Silver
Tally
T
Naveh-Many
D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D051496:Receptor, Fibroblast Growth Factor, Type 1