Endocrine Regulation of Phosphate Homeostasis

Phosphate, a component of nucleic acids, DNA and RNA, is incorporated in the structure of phospholipids in cell membranes, and is involved in many biological functions such as cell signaling, energy metabolism, and bone mineralization. Phosphate homeostasis is regulated by intestinal phosphate absorption, renal phosphate reabsorption, and skeletal phosphate resorption. Renal and intestinal transport of inorganic phosphate is controlled by sodium-phosphate cotransporters. Endocrine regulators that target bone, kidneys, and intestines during phosphate homeostasis include parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23), and Klotho. Dysregulated serum phosphate falls within two categories: hypophosphatemia and hyperphosphatemia. Some genetic disorders such as hypophosphatemic rickets overexpress FGF23, inhibiting renal reabsorption of inorganic phosphate, while other disorders such as familial tumor calcinosis inhibit the expression of FGF23, causing hyperphosphatemia. Conditions associated with phosphate toxicity include chronic kidney disease, vascular calcification, tumorigenesis, and premature aging.