Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

Stephen J. Quinn, Alex R.B. Thomsen, Jian L. Pang, Lakshmi Kantham, Hans Bräuner-Osborne, Martin Pollak, David Goltzman, Edward M. Brown

Research output: Contribution to journalArticle

Abstract

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range.

Original languageEnglish (US)
Pages (from-to)E310-E320
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume304
Issue number3
DOIs
StatePublished - Feb 1 2013

Keywords

  • 1,25-dihydroxyvitamin D
  • Calcium × phosphorus product
  • Calcium-sensing receptor
  • Fibroblast growth factor 23
  • Parathyroid hormone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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  • Cite this

    Quinn, S. J., Thomsen, A. R. B., Pang, J. L., Kantham, L., Bräuner-Osborne, H., Pollak, M., Goltzman, D., & Brown, E. M. (2013). Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo. American Journal of Physiology - Endocrinology and Metabolism, 304(3), E310-E320. https://doi.org/10.1152/ajpendo.00460.2012