preproPTH

PreproPTH refers to the precursor form of parathyroid hormone (PTH) as encoded by the PTH gene. It is synthesized as a single-chain polypeptide that contains an N-terminal signal peptide and a downstream pro-region. This prepro form is directed to the secretory pathway in parathyroid cells.

Proteolytic processing in the endoplasmic reticulum and Golgi apparatus removes the signal peptide to generate proPTH, which is further cleaved by endopeptidases to produce mature PTH (1-84). Some secretory pathways may also yield additional PTH-related fragments. The mature hormone is stored in secretory vesicles and released by chief cells in response to physiologic cues such as low blood calcium.

Functionally, active PTH binds to the PTH1R receptor on bone and kidney cells. In bone, it promotes osteoblast-driven expression of RANKL, leading to osteoclast-mediated bone resorption and release of calcium. In the kidney, it increases calcium reabsorption in the distal tubules and decreases phosphate reabsorption in the proximal tubule. It also stimulates the production of calcitriol (1,25-dihydroxyvitamin D) by upregulating 1α-hydroxylase, which enhances intestinal calcium absorption. PTH secretion is tightly regulated by the calcium-sensing receptor, increasing when calcium is low and decreasing as calcium rises.

Clinical relevance centers on disorders of PTH excess or deficiency. Primary hyperparathyroidism involves elevated PTH and hypercalcemia, while hypoparathyroidism involves reduced PTH and hypocalcemia. Understanding preproPTH and its processing helps explain how biosynthesis and secretion of PTH are coordinated to maintain calcium homeostasis.