PTH3R

PTH3R (parathyroid hormone 3 receptor) is a class B1 G protein-coupled receptor within the PTH/PTHrP signaling system and represents an additional receptor lineage identified in teleost fish and several non-mammalian vertebrates beyond the mammalian PTH1R and PTH2R receptors^[1][2]. Mechanistically, PTH3R participates in endocrine and developmental signaling through ligand-dependent activation of intracellular pathways linked to cAMP accumulation, placing it within the broader regulatory network controlling calcium homeostasis and tissue development^[1]. Experimental studies demonstrated that receptor activation is mediated by members of the PTH-family peptide group, and ligand stimulation can trigger intracellular signaling responses characteristic of PTH/PTHrP receptors^[1]. In developmental and physiological models, pth3r expression is detected during early zebrafish development and shows dynamic regulation under environmental stress conditions, supporting its utility for investigating vertebrate developmental biology and adaptive responses^[3]. Disease-oriented evidence for PTH3R remains limited compared with mammalian PTH1R; therefore, current research applications are primarily centered on developmental, evolutionary, and comparative endocrine biology models rather than direct human disease mechanisms^[1][3]. Compared with related isoforms, PTH3R displays distinct ligand preferences and tissue-expression patterns, suggesting functional divergence after receptor duplication during vertebrate evolution^[1][2]. For experimental applications, receptor stimulation assays have shown that PTH-family peptides activate PTH3R in a dose-dependent manner, providing a practical platform for dissecting receptor selectivity, signaling specificity, and PTH/PTHrP pathway evolution^[1].