NYMC Faculty Publications


Acute Parathyroid Hormone Injection Increases c-Terminal, but Not Intact Fibroblast Growth Factor 23 Levels

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The acute effects of PTH on FGF23 in vivo are not well understood. After a single s.c. PTH(1-34) injection (50nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/C-terminal FGF23 (cFGF23). Furthermore, FGF23 mRNA and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by 3-5-fold within two hours following PTH injection, which returned to baseline by 4 hours. In contrast, iFGF23 levels remained unchanged for the first two hours, yet declined to approximately 60% by 6 hours and remained suppressed before returning to baseline after 24 hrs. Using homozygous mice for an ADHR-FGF23 mutation or animals treated with a furin inhibitor, we showed that cFGF23 and iFGF23 levels increased equivalently after PTH injection. These findings are consistent with increased FGF23 production in bone, yet rapid cleavage of the secreted intact protein. Using primary osteocyte-like cell cultures, we showed that PTH increased FGF23 mRNA expression through cAMP/PKA, but not IP3/PKC signaling; PTH also increased furin protein levels. In conclusion, PTH injection rapidly increases FGF23 production in bone in vivo and in vitro. However, intact FGF23 is rapidly degraded. At later time-points through an unidentified mechanism a sustained decrease in FGF23 production occurs.