Parathyroid Anatomy, Hormone Synthesis, Secretion, Action, and Receptors

Abstract Parathyroid hormone (PTH) is produced in the parathyroid glands and is released as an 84 amino acid polypeptide whose bioactivity resides in its amino-terminal domain. PTH secretion is controlled by the parathyroid calcium-sensing receptor (CaSR), and inactivating or activating mutations in this receptor lead to inherited hypercalcaemic and hypocalcaemic disorders, respectively. PTH regulates extracellular fluid calcium homeostasis through its renal calcium-conserving action, and its bone resorbing actions. Adenomas or hyperplasia of the parathyroid glands can lead to dysregulated PTH secretion and the disorder hyperparathyroidism. Intermittently administered PTH, however, exerts a bone anabolic effect and has found use in the clinic in the treatment of osteoporosis. Both PTH (and the gene family member, parathyroid hormone-related protein or PTHrP) act through a G-protein-coupled receptor, the type 1 PTH/PTHrP receptor (PTHR1) that is widely expressed and signals through multiple second messenger pathways. Inactivating mutations in the PTHR1 cause Blomstrand’s lethal chondrodysplasia, whereas activating mutations are found in Jansen’s metaphyseal chondrodysplasia.