The phosphatonins and the regulation of phosphate transport and vitamin D metabolism

Stacy Sommer, Theresa Berndt, Theodore Craig, Rajiv Kumar

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Phosphate homeostasis is preserved during variations in phosphate intake by short-term intrinsic renal and intestinal adaptations in transport processes, and by more long-term hormonal mechanisms, which regulate the efficiency of phosphate transport in the kidney and intestine. Recently, several phosphaturic peptides such as fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein-4 (sFRP-4), extracellular phosphoglycoprotein (MEPE) and fibroblast growth factor 7 (FGF-7) have been shown to play a pathogenic role in several hypophosphatemic disorders such as tumor-induced osteomalacia (TIO), autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), the McCune-Albright syndrome (MAS) and fibrous dysplasia (FD). These proteins induce phosphaturia and hypophosphatemia in vivo, and inhibit sodium-dependent renal phosphate transport in cultured renal epithelial cells. Interestingly, despite the induction of hypophosphatemia by FGF-23 and sFRP-4 in vivo, serum 1, 25-dihydroxyvitamin D (1α,25(OH)2D) concentrations are decreased or remain inappropriately normal, suggesting an inhibitory effect of these proteins on 25-hydroxyvitamin D 1α-hydroxylase activity. In FGF-23 knockout mice, 25-hydroxyvitamin D 1α-hydroxylase expression is increased and elevated serum 1α,25(OH)2D levels cause significant hypercalcemia and hyperphosphatemia. MEPE, however, increases circulating 1α,25(OH)2D. Circulating or local concentrations of these peptides/proteins may regulate 25-hydroxyvitamin D 1α-hydroxylase activity in renal tissues under physiologic circumstances.

Original languageEnglish (US)
Pages (from-to)497-503
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume103
Issue number3-5
DOIs
StatePublished - Mar 2007

Keywords

  • 1, 25-Dihydroxyvitamin D (1α,25(OH)D)
  • 25-Hydroxyvitamin D 1α-hydroxylase
  • Autosomal dominant hypophosphatemic rickets (ADHR)
  • Fibroblast growth factor 23
  • Matrix extracellular phosphoglycoprotein and fibroblast growth factor 7
  • Phosphate
  • Phosphate (Pi)
  • Secreted frizzled related protein-4
  • Tumor-induced osteomalacia
  • X-linked hypophosphatemic rickets (XLH)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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