Renal and Skeletal Actions of Parathyroid Hormone (PTH) and PTH-Related Protein

Abstract

This chapter reviews the various mechanisms through which parathyroid hormone (PTH) and PTH-related protein (PTHrP) control renal tubular epithelial function. The kidney is the focal point for the physiological regulation of mineral ion homeostasis by circulating parathyroid hormone (PTH). By directly controlling renal tubular reabsorption of calcium and phosphate and the synthesis of 1,25 (OH) 2 D, PTH exerts control over both intestinal absorption and urinary excretion of these key mineral ions. Renal tubular responses to PTH deficiency, PTH or PTHRP excess, or defects in function of the type-1 FFH/FFHrP receptor (PTHR) lead to alterations in blood calcium, phosphate, or 1,25 (OH) 2 D that are the hallmarks of numerous clinical disorders. As the PTHR recognizes the active amino termini of both ligands equivalently, it is likely that the effects described for PTH would pertain to PTHrP as well. As in other PTH/FFHRP target cells, the responsiveness of renal epithelial cells to PTH or PTHRP may be regulated, both by previous or chronic exposure to the homologous ligand and by other agonists that do not interact directly with the PTHR. Several factors may contribute to this renal resistance to PTHR activation, including a reduced number of cell surface PTHRs, persistent occupancy of PTHRs by ligand, and defective coupling between available PTHRs and the G proteins that mediate activation of effectors such as adenylyl cyclase or PLC. Administration of PTH in vivo also increases the net renal reabsorption of both Ca 2+ and Mg 2+ .