Phosphatonins: a new class of phosphate-regulating proteins.
OBJECTIVE
There is an intimate relationship between phosphate and calcium homeostasis throughout the animal kingdom. One traditional assumption is that all phosphate-regulating hormones are primarily calcium-regulating hormones. Although the notion of a circulating substance dedicated to phosphate homeostasis has existed for more than a decade, it is not until recently that these hormones have been identified. The molecular characterization of these substances will prove to be critical for understanding phosphate physiology and clinical disorders of phosphate metabolism.


RESULTS
This review will focus primarily on the first two proteins recently shown to have phosphatonin properties. Using three human diseases as models and a combination of positional cloning and differential gene expression, fibroblast growth factor 23 and frizzled-related protein 4 were shown to be associated with one or more of these diseases. Although both of these substances have phosphaturic action, their biological effects are likely to extend beyond epithelial phosphate transport.


CONCLUSIONS
The phosphatonins are a growing family of substances that may act on multiple organs in autocrine, paracrine, and endocrine modes to regulate phosphate metabolism. As this list expands, the need for a more rigid definition of the term phosphatonin becomes evident. The identification and characterization of these phosphate-regulatory compounds will provide a clearer understanding of how individual phosphatonins regulate phosphate in normal and disease physiology.
Schiavi
Susan C
SC
Applied Genomics, Genzyme Corporation, One Mountain Road, Framingham, Massachusetts 01701, USA. susan.schiavi@genzyme.com
Moe
Orson W
OW
D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*
D010710:Phosphates; D011506:Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23