The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases

Abstract

Parathyroid hormone (PTH) plays a key role in the regulation of calcium-phosphate metabolism. The secretion of PTH is regulated by calcium-sensing receptor (CaSR), which primarily expressed in the parathyroid glands and the renal tubules of the kidney. Increase of calcium concentration in extracellular matrix of cells is causing activation of the CaSR. Activated CaSR inhibits secretion of PTH and increases urinary calcium excretion. All CaSR effects leads to prevent development of hypercalcemia complications. Downregulation of the CASR expression and/or altered CaSR functioning leads to dysregulation of PTH synthesis. It may be the underlying cause of the development of primary and secondary hyperparathyroidism, as well as a number of hereditary diseases associated with loss- and gain-of-function mutations of the CaSR. In this paper we discusses the function of the CaSR in physiology and also the potential mechanisms that can impaired CaSR-induced signaling in various calcitropic diseases.