Three feedback loops precisely regulating serum phosphate concentration.

Parathyroid hormone (PTH) and vitamin D were considered the major factors regulating phosphate homeostasis. Now, with the identification of fibroblast growth factor 23 (FGF23), a phosphaturic molecule inhibiting calcitriol and PTH, they need to be integrated into three feedback loops involving parathyroid, bone, and kidney. PTH and calcitriol are required for the appropriate synthesis of FGF23 by bone cells. PTH also regulates klotho expression in the kidney and thereby the phosphaturic action of FGF23.