40 - Hormonal Regulation of Calcium and Phosphate Metabolism

Abstract

Plasma calcium is normally maintained within very narrow limits. Plasma calcium is balanced by the rate of calcium absorption from the gastrointestinal tract, the rates of bone formation and resorption, and renal excretion. The major physiological hormones regulating plasma calcium are parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D. PTH stimulates osteoclastic bone resorption, increases renal calcium reabsorption in the distal tubule, and indirectly stimulates intestinal calcium absorption. Secretion of PTH by the parathyroid gland is tightly and inversely regulated by plasma ionized calcium levels. Vitamin D, which is synthesized in skin by UVB light or acquired in the diet, is hydroxylated to 25-hydroxyvitamin D in the liver and activated by renal 1α-hydroxylase to 1,25-dihydroxyvitamin D. The production of 1,25-dihydroxyvitamin D is stimulated by PTH and hypophosphatemia. 1,25-Dihydroxyvitamin D enhances intestinal calcium absorption, modestly increases intestinal phosphate absorption, and also stimulates osteoclastic bone resorption. Plasma phosphate is determined by the rate of absorption by the gastrointestinal tract, soft tissue influx and efflux, bone formation and resorption, and renal excretion. Plasma phosphate levels are regulated by PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23 (FGF23). PTH and FGF23 both inhibit phosphate reabsorption by the proximal tubule. This allows PTH to correct a hypocalcemic challenge without elevating plasma phosphate levels. FGF23 production by osteocytes is increased in response to hyperphosphatemia. These three hormones act in a coordinated manner in response to perturbations in plasma calcium and phosphate to maintain normocalcemia and normophosphatemia.