Figure 2. Corticotropin-releasing hormone receptor subtypes, splice variants and tissue distribution. CRH-R: Corticotropin-releasing hormone receptor, TM: transmembrane. CRH is considered the specific endogenous ligand for CRH-R1, while Urocortin 2 and Urocortin 3 are considered the specific endogenous ligands of CRH-R2. Urocortin 1 is considered an endogenous ligand for both subtypes of the receptor. CRH binds to CRH-R2 with an affinity that is 100-fold lower compared to the binding affinity of the urocortines.