Phosphatonins and the regulation of phosphate homeostasis

Theresa Berndt, Rajiv Kumar

Research output: Contribution to journalReview articlepeer-review

173 Scopus citations


Inorganic phosphate (Pi) is required for energy metabolism, nucleic acid synthesis, bone mineralization, and cell signaling. The activity of cell-surface sodium-phosphate (Na+-Pi) cotransporters mediates the uptake of Pi from the extracellular environment. Na +-Pi cotransporters and organ-specific Pi absorptive processes are regulated by peptide and sterol hormones, such as parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D (1α,25(OH)2D3), which interact in a coordinated fashion to regulate Pi homeostasis. Recently, several phosphaturic peptides such as fibroblast growth factor-23 (FGF-23), secreted frizzled related protein-4 (sFRP-4), matrix extracellular phosphoglycoprotein, and fibroblast growth factor-7 have been demonstrated to play a pathogenic role in several hypophosphatemic disorders. By inhibiting Na+-Pi transporters in renal epithelial cells, these proteins increase renal P i excretion, resulting in hypophosphatemia. FGF-23 and sFRP-4 inhibit 25-hydroxyvitamin D 1α-hydroxylase activity, reducing 1α,25(OH)2D3 synthesis and thus intestinal P i absorption. This review examines the role of these factors in Pi homeostasis in health and disease.

Original languageEnglish (US)
Pages (from-to)341-359
Number of pages19
JournalAnnual Review of Physiology
StatePublished - 2007


  • 1α,25-dihydroxyvitamin D
  • Fibroblast growth factor-23
  • Fibroblast growth factor-7
  • Matrix extracellular phosphoglycoprotein
  • Parathyroid hormone
  • Phosphatonins
  • Secreted frizzled related protein-4
  • Sodium-phosphate cotransporters

ASJC Scopus subject areas

  • Physiology


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