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

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):497-503. doi: 10.1016/j.jsbmb.2006.11.010. Epub 2007 Jan 16.

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 (1alpha,25(OH)(2)D) concentrations are decreased or remain inappropriately normal, suggesting an inhibitory effect of these proteins on 25-hydroxyvitamin D 1alpha-hydroxylase activity. In FGF-23 knockout mice, 25-hydroxyvitamin D 1alpha-hydroxylase expression is increased and elevated serum 1alpha,25(OH)(2)D levels cause significant hypercalcemia and hyperphosphatemia. MEPE, however, increases circulating 1alpha,25(OH)(2)D. Circulating or local concentrations of these peptides/proteins may regulate 25-hydroxyvitamin D 1alpha-hydroxylase activity in renal tissues under physiologic circumstances.

MeSH terms

  • Animals
  • Biological Factors / metabolism*
  • Biological Transport
  • Diet
  • Fibroblast Growth Factors / metabolism
  • Homeostasis
  • Humans
  • Kidney / metabolism
  • Phosphates / metabolism*
  • Phosphorus / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Vitamin D / metabolism*

Substances

  • Biological Factors
  • Phosphates
  • Proto-Oncogene Proteins
  • Vitamin D
  • Phosphorus
  • Fibroblast Growth Factors