Adhesion G protein-coupled receptor D1 (ADGRD1)

Adhesion G protein-coupled receptor D1 (ADGRD1 or GPR133) is a member of the adhesion subfamily of G protein-coupled receptors, characterized by a long N-terminal extracellular domain and classical seven-transmembrane architecture. ADGRD1 is a membrane receptor that binds androgens, especially 5α-dihydrotestosterone, leading to Gs protein-mediated signaling and activation of adenylyl cyclase—a process that elevates intracellular cAMP[3][7]. Physiologically, ADGRD1 is critical in the reproductive system for regulating embryo transit through the oviduct, and it also modulates muscle function by enhancing muscle strength in response to androgen binding[1][7]. Pathologically, ADGRD1 is upregulated in certain cancers (notably glioblastoma and lung adenocarcinoma), where it contributes to tumor development and progression or, contextually, may suppress cell proliferation through altered cell cycle regulation[1]. ADGRD1 genetic variants are also linked with diverse phenotypic traits, including adult height, metabolism, and cardiovascular function[1]. ADGRD1 is considered an emerging therapeutic target, although there are currently no approved drugs that antagonize or modulate this receptor beyond activation by endogenous androgens and experimental agonists[3][4][7].

Other names

GPR133PGR25Adhesion G-protein coupled receptor D1G-protein coupled receptor 133G-protein coupled receptor PGR25Probable G-protein coupled receptor 133

Receptor agonism by androgens (e.g., 5α-DHT) leads to Gs protein coupling, activation of adenylyl cyclase, and rise in cAMP[3][7]. Methenolone acts as an agonist and can activate ADGRD1 signaling, though mechanisms may parallel those of androgens[3].