Corticotrophin-releasing factor (CRF) is a peptide hormone and a key regulator of the stress response. Through activation of the hypothalamic–pituitary axis and its role as a neurotransmitter, CRF influences a wide range of physiological responses, including appetite control, cardiovascular regulation, glucose metabolism, immune function and behavior.

Corticotrophin-releasing factor receptor 1 (CRHR1, CRF1) is a member of the class B G-protein coupled receptors. CRHR1 is activated by CRF. It is expressed in brain areas including the hypothalamus, pituitary, amygdala and cortex. The core fold of the receptor features seven transmembrane helices (TM1-TM7). The connecting loops lack secondary structure apart from one extracellular loop- ECL1. In contrary to A Class GPCRs, CRF1 has a pronounced V-shape and a large cavity hypothesized to be the peptide binding site. The cytoplasmic half of TM3 and TM5 interacts with G_s. Small molecule antagonists of the receptor, such as CP-376395, act allosterically by maintaining the receptor in its inactive state at a site different from the peptide binding site. Interestingly, although CP-376395 is highly selective for CRHR1, all of the residues found to interact directly with this ligand are conserved between CRHR1 and CRHR2¹.

Interaction between childhood trauma and sequence variation in the CRHR1 gene that increase risk for affective disorders has been established by several studies. In Rhesus macaques, single nucleotide polymorphisms affecting exon 6 of CRHR1 gene influence anxious temperament (a phenotype that predicts the development of human anxiety and depressive disorder) and brain metabolism².