Corticotropin-Releasing Factor Receptor 1 Antibodies

Corticotropin-releasing factor receptor 1 (CRF₁), encoded by CRHR1, is a class B1 G protein-coupled receptor activated by corticotropin-releasing factor (CRF, also known as CRH) and urocortin 1. It couples predominantly to Gs, stimulating adenylyl cyclase and increasing intracellular cAMP. CRF₁ is expressed in anterior pituitary corticotrophs and in brain regions involved in stress and emotional processing, including the cortex and amygdala. In the pituitary, CRF₁ activation stimulates adrenocorticotropic hormone (ACTH) release, which in turn drives adrenal cortisol secretion. In the brain, CRF₁ signaling contributes to behavioral and autonomic responses to stress. Sustained agonist exposure can induce receptor desensitization, β-arrestin recruitment, and clathrin-mediated internalization. The selective oral CRF₁ antagonist crinecerfont reduces ACTH-driven adrenal androgen production. In the United States, crinecerfont is approved as an adjunct to glucocorticoid replacement to control androgen levels in patients aged four years and older with classic congenital adrenal hyperplasia. CRF1 receptor desensitization, β-arrestin recruitment and internalization are regulated by phosphorylation of carboxyl-terminal threonine428/serine429 (pT428/pS429-CRF1), threonine431 (pT431-CRF1) and serine434/serine437 (pS434/pS437-CRF1). This nomenclature refers to the human CRF1 receptor. This phosphorylation motif is highly conserved across species but corresponds to pT399/pS400-CRF1, pT402/pS405-CRF1 and pS408/pS412-CRF1 in mice and rats. Interestingly, a very similar phosphorylation motif is present in the human CRF2 receptor which corresponds to pT395/pS396-CRF2, pT398/pS401-CRF2 and pS404/pT408-CRF2. For more information on CRF1 pharmacology please refer to the IUPHAR database. For further reading refer to:

Hauger RL, Grigoriadis DE, Dallman MF, Plotsky PM, Vale WW, Dautzenberg FM. International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands. Pharmacol Rev. 2003 Mar;55(1):21-6. doi: 10.1124/pr.55.1.3. PMID: 12615952.