Parathyroid hormone 1 receptor (PTH1R)

The Parathyroid hormone 1 receptor (PTH1R) is a Class B G protein-coupled receptor that plays a central role in mineral ion homeostasis and skeletal development. It is primarily expressed in osteoblasts and renal tubular cells, where it mediates the actions of both parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) [1][2]. Upon ligand binding at the extracellular domain and transmembrane bundle interface, PTH1R activates Gs-adenylyl cyclase and Gq-phospholipase C pathways, regulating calcium reabsorption and bone turnover [3]. In the context of disease, PTH1R is a validated therapeutic target for osteoporosis; intermittent activation by synthetic analogs like abaloparatide (a PTHrP analog) or teriparatide (a PTH fragment) stimulates osteoblastic activity and increases bone mineral density [4][5]. Conversely, loss-of-function mutations in PTH1R lead to Blomstrand chondrodysplasia, while gain-of-function mutations cause Jansen's metaphyseal chondrodysplasia [2]. Understanding the specific ligand-binding interface is crucial for developing selective modulators that can bias signaling toward anabolic bone formation while minimizing resorptive effects [6].

Other names

PTH/PTHrP receptorParathyroid hormone receptor 1PTHR1

Agonism of the receptor leading to activation of Gs-adenylyl cyclase and Gq-phospholipase C signaling pathways.