Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23

In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney...

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Published in:Annual review of medicine 2010-01, Vol.61 (1), p.91-104
Main Authors: Bergwitz, Clemens, Jüppner, Harald
Format: Article
Language:English
Subjects:
Calcitriol - physiology
Calcium
Fibroblast Growth Factors - physiology
Homeostasis - physiology
Hormones
Humans
Medical research
Parathyroid Hormone - physiology
Phosphates
Phosphates - blood
Phosphorus
Phosphorus Metabolism Disorders - etiology
Thyroid gland
Vitamin D
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Summary:In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal phosphate excretion by reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Most insights gained into the regulation of phosphate homeostasis by these factors are derived from human genetic disorders and genetically engineered mice, which are reviewed in this paper.
ISSN:0066-4219
1545-326X
DOI:10.1146/annurev.med.051308.111339