Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23
By Clemens Bergwitz, H. Jüppner. Annual Review of Medicine, 2010
695 citations recorded by the source corpus.
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)2D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)2D 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)2D, 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.
Subfields: Genetics, Molecular Biology, Nephrology
View Paper: https://www.semanticscholar.org/paper/e0564d77809166e96d3f5ee97b8c4fa0a059f265
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Citations in the corpus
- Molecular Mechanisms of Vitamin D Action (2012, background): “CYP24A1 is induced by FGF23 [41] as well as by the 1,25D hormone, with potent VDREs identified in the CYP24A1 gene (Table 1).”
- Immunologic Effects of Vitamin D on Human Health and Disease (2020, background): “In addition, 1,25(OH)2D forms an endocrine system together with parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) to regulate calcium and phosphate homeostasis [8].”