The Calcium-Sensing Receptor and the Parathyroid: Past, Present, Future

Parathyroid hormone (PTH) defends the extracellular fluid from hypocalcemia and has powerful and well-documented actions on the skeleton and renal tubular system. To achieve a satisfactory stable plasma calcium level, the secretion of PTH, and the resulting serum PTH level, is titrated carefully to the prevailing plasma ionized Ca²⁺ concentration via a Ca²⁺ sensing mechanism that mediates feedback inhibition of PTH secretion. Herein, I consider the properties of the parathyroid Ca²⁺ sensing mechanism, the identity of the Ca²⁺ sensor, the intracellular biochemical mechanisms that it controls, the manner of its integration with other components of the PTH secretion control mechanism, and its modulation by other nutrients. Together the well-established, recently elucidated, and yet-to-be discovered elements of the story constitute the past, present, and future of the parathyroid and its calcium-sensing receptor (CaSR).