PTH1R

PTH1R (parathyroid hormone 1 receptor) is a class B G protein-coupled receptor that mediates signaling by both parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP), thereby regulating skeletal development, bone turnover, and mineral ion homeostasis.^[1] PTH1R is predominantly expressed in osteoblasts, osteocytes, and renal tubular cells, positioning it as a central regulator of bone-kidney endocrine communication.^[1][2] Mechanistically, PTH1R activation engages multiple intracellular pathways, including the Gαs-adenylyl cyclase-cAMP-protein kinase A axis and additional G protein-dependent signaling cascades that control gene expression and cellular responses in target tissues.^[3] In bone, PTH1R signaling in osteocytes regulates expression of key remodeling mediators, including RANKL and SOST/sclerostin, thereby coordinating both osteoclast-mediated resorption and osteoblast-mediated bone formation.^[4][5] Genetic studies further demonstrate that osteocytic PTH1R signaling is required for full anabolic and catabolic skeletal responses to PTH, highlighting its importance in bone remodeling and osteoporosis-related research models.^[5][6] Disease relevance is underscored by the established role of PTH1R in mineral metabolism and skeletal homeostasis, processes that are disrupted in metabolic bone disorders.^[1][3] Compared with the related receptor PTH2R, which is primarily expressed in the central nervous system and other non-skeletal tissues, PTH1R functions as the principal receptor mediating the classical actions of both PTH and PTHrP in bone and kidney.^[7] For experimental applications, PTH1R-targeting agonists such as teriparatide activate receptor signaling in osteoblast-lineage cells and osteocytes and are widely used to investigate osteoanabolic mechanisms and skeletal remodeling responses.^[8]

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