Corticotropin-Releasing Factor Receptor Antibodies

The corticotropin-releasing factor receptor family comprises two class B1 G protein-coupled receptors, CRF₁ and CRF₂, encoded by CRHR1 and CRHR2, respectively. Corticotropin-releasing factor (CRF, also known as CRH) preferentially activates CRF₁, urocortin 1 activates both subtypes, and urocortins 2 and 3 preferentially activate CRF₂. Both receptors signal predominantly through Gs, stimulating adenylyl cyclase and increasing intracellular cAMP. CRF₁ is expressed in anterior pituitary corticotrophs and throughout the central nervous system, where it participates in endocrine and behavioral responses to stress. In the pituitary, CRF₁ activation stimulates adrenocorticotropic hormone (ACTH) release and thereby drives adrenal cortisol secretion. CRF₂ is expressed in selected brain regions and peripheral tissues, including the heart and vasculature, where it contributes to cardiovascular regulation. Agonist exposure can induce receptor desensitization and internalization, with trafficking patterns that vary by receptor subtype and ligand. The oral CRF₁ antagonist crinecerfont is approved in the United States as an adjunct to glucocorticoid replacement to control androgen levels in patients aged four years and older with classic congenital adrenal hyperplasia. The CRF₂-selective agonist urocortin 2 has been evaluated in early clinical studies in heart failure, and no CRF₂-selective drug is currently approved for therapeutic use.