PTH

Peptide hormone secreted by parathyroid chief cells that acts as a primary endocrine regulator of extracellular calcium and phosphate homeostasis, acting primarily on bone and kidney to maintain serum calcium levels within a narrow range. Acts by binding and activating the G protein-coupled receptor PTH1R, engaging the receptor to activate G(s)-mediated cAMP/PKA signaling and G(q)-mediated PLC/PKC signaling. In bone, acts indirectly on osteoclasts by binding PTH1R on cells of the osteoblast/osteocyte lineage, where it increases expression of TNFSF11/RANKL and decreases expression of TNFRSF11B/OPG, thereby raising the RANKL/OPG ratio and stimulating osteoclast differentiation and bone resorption. Stimulates also [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells. In distal renal tubule cells, stimulates active Ca(2+) reabsorption via the adenylyl cyclase-cAMP-protein kinase A (PKA) pathway leading to the phosphorylation and activation of the calcium selective cation channel TRPV5. Acting on PTH1R in proximal renal tubule cells, decreases reabsorption of filtered phosphate by reducing apical abundance of SLC34A1, through a mechanism involving PTH1R-activated PKC-mediated phosphorylation of the scaffold NHERF1, causing dissociation of the NHERF1-SLC34A1 complex and subsequent clathrin-mediated endocytosis and lysosomal degradation of the cotransporter (By similarity). Activates also transcription of CYP27B1 (25-hydroxyvitamin D3 1-alpha-hydroxylase) through a cAMP/PKA/SIK2-SIK3/CRTC2 axis, thereby increasing renal synthesis of the active vitamin D metabolite 1,25-dihydroxyvitamin D(3) (By similarity)..

Function from UniProtKB (P01270), read 2026-09-23. CC BY 4.0.