Corticotropin-releasing hormone receptor (CRHR) (CRHR)

The Corticotropin-releasing hormone receptor (CRHR) is a Class B G protein-coupled receptor that serves as a primary regulator of the hypothalamic-pituitary-adrenal (HPA) axis and the mammalian response to stress (UniProt: P34998). It exists in two distinct subtypes, CRHR1 and CRHR2, which are distributed throughout the brain and peripheral tissues, including the pituitary gland, heart, and gastrointestinal tract (IUPHAR/BPS Guide to Pharmacology). CRHR1 is the predominant subtype in the anterior pituitary, where its activation by CRH triggers the secretion of adrenocorticotropic hormone (ACTH), leading to the production of cortisol and androgens by the adrenal glands. Dysregulation of CRHR signaling is implicated in a wide range of pathologies, including major depressive disorder, generalized anxiety disorder, irritable bowel syndrome, and congenital adrenal hyperplasia (CAH) (PubMed: 15505536). In the context of CAH, CRHR1 antagonists like crinecerfont and tildacerfont are being developed to lower ACTH levels and reduce adrenal androgen excess, potentially allowing for a reduction in exogenous glucocorticoid doses (PubMed: 32813487). This receptor remains a high-priority target for drug development in both endocrinology and psychiatry due to its central role in modulating the physiological and behavioral effects of stress.

Other names

CRH receptorCRF receptorCorticotropin-releasing factor receptorCRHR1CRHR2

Antagonism of the CRHR1 receptor subtype to inhibit the secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland, thereby reducing the production of adrenal steroids such as cortisol and androgens (PubMed: 32813487).