Hormonal regulation of phosphate balance

Abstract

Phosphate homeostasis is maintained by intestine, bone, and kidney, which is regulated by many hormones. In addition to classical hormones such as parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25 (OH) (2)D] , fibroblast growth factor 23 (FGF23) and Klotho have been discovered as novel factors for phosphate metabolism. FGF23 is a circulating hormone that is synthesized by osteocytes and osteoblasts in bone. The physiological actions of FGF23 are to promote phosphaturia and decrease production of 1,25 (OH) (2)D. Klotho was initially identified as an anti-aging protein, but subsequent research revealed multiple functions of Klotho in phosphate metabolism. Klotho directly binds to FGF receptor 1 (FGFR1) and contributes to FGFR1-Klotho complex-mediated signal transduction with higher affinity than FGFR1 or Klotho alone. In addition, the extracellular domain of Klotho is clipped by enzymes and secreted into blood, which exerts phosphaturic effects independently of FGF23. In the regulation of phosphate metabolism, this FGF23-Klotho axis constitutes feedback loops with classical factors such as PTH and 1,25 (OH) (2)D. However, the precise feedback system in the phosphate metabolism remains to be determined and further research is required to provide a greater understanding of the phosphate metabolism system.