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A simple bone shape releasing a coiled hormone chain that docks onto a receptor with a small Klotho wedge on a cell edge, as phosphate dots stream away.

Fibroblast Growth Factor 23 (FGF23)

4 of 6~2 min readReviewed

Calcium and Phosphate Homeostasis

Fibroblast growth factor 23, or FGF23, is a hormone of the FGF19 family that is mainly produced by bone cells, in particular osteoblasts and osteocytes. Its main job is to lower phosphate, and it also restrains calcitriol, the active form of vitamin D.

Effects

The main effects of FGF23 are:

  • at the kidney: promotion of phosphorus excretion and inhibition of calcitriol formation; the mechanism behind the increase of phosphorus excretion is down-regulation of the phosphorus transporters located in the proximal convoluted tubule (PCT)
  • at the intestine: reduction of phosphorus absorption by the intestine, largely because the fall in calcitriol removes the signal that drives intestinal phosphate absorption

Because it removes phosphate through the urine at the same time as it reduces the phosphate taken up from the gut, FGF23 moves phosphate in the same direction at both ends of the balance.

A central FGF23 chain sending short arrows to a kidney shape with a urine outlet and to an intestine tube, both marked to lower phosphate.
FGF23 lowers phosphate at both ends, raising its excretion by the kidney and reducing its absorption by the intestine.

Receptor and Klotho

The receptor of FGF23 is an IG-like domain-containing receptor that has three IG-like parts; the FGFR (fibroblast growth factor receptor) is a tyrosine kinase receptor. An important co-receptor for the FGFR is the Klotho domain, which plays an important role in the activation and signal transduction of FGF23.

Processing of the hormone

The first protein product of FGF23 is a pre-protein of 251 amino acids that is cleaved into an N-terminal core and a smaller C-terminal part, which together make the active FGF23. Active FGF23 is extensively O-glycosylated, which makes it resistant to proteolysis. The fragments that are made by the proteolysis of FGF23 are the physiological antagonists of the active molecule.

What releases FGF23

FGF23 is released in response to:

  • high phosphate
  • high PTH
  • high calcitriol

In iron deficiency the level of FGF23 expression is increased, which is mostly devoted to the carboxy-terminal FGF23, or cFGF23.

Since calcitriol both drives FGF23 release and is restrained by it, the way calcitriol is made, activated and regulated is the remaining piece of the axis.