Corticotropin-releasing hormone receptor 1 (CRHR1) (CRHR1)

The Corticotropin-releasing hormone receptor 1 (CRHR1) is a G protein-coupled receptor that plays a pivotal role in the mammalian stress response by mediating the effects of Corticotropin-releasing hormone (CRH) (UniProt P34998). Located primarily in the anterior pituitary and various brain regions, CRHR1 activation triggers the hypothalamic-pituitary-adrenal (HPA) axis, leading to the secretion of adrenocorticotropic hormone (ACTH) and subsequent cortisol release (StatPearls, 2023). Dysregulation of CRHR1 signaling is strongly linked to psychiatric conditions such as major depressive disorder and anxiety, as well as metabolic and endocrine disorders like congenital adrenal hyperplasia (CAH) (PubMed, PMID: 15505131). In CAH, CRHR1 antagonists are used to suppress the overactive HPA axis and reduce the production of excess adrenal androgens (ClinicalTrials.gov, NCT04457336). While several CRHR1 antagonists, including pexacerfont and verucerfont, were initially investigated for anxiety and depression, recent clinical focus has shifted toward their efficacy in treating endocrine disorders (PubMed, PMID: 32651474). Safety considerations for targeting this receptor include potential HPA axis suppression and historical concerns regarding hepatotoxicity observed with certain early-generation compounds (PubMed, PMID: 21718214).

Other names

Corticotropin-releasing hormone systemCRH systemCRF systemCorticotropin-releasing factor receptor 1CRFR1CRF1 receptor

Antagonism of the CRHR1 receptor to inhibit the release of adrenocorticotropic hormone (ACTH) and subsequent cortisol or adrenal androgens.