Crhr1, the corticotropin-releasing hormone receptor 1, is a G protein-coupled receptor. It is crucial for the signaling of corticotropin-releasing hormone (CRH) in the hypothalamic-pituitary-adrenal (HPA) axis and extrahypothalamic brain circuits. CRH acts as a neuromodulator, and Crhr1 is involved in organizing behavioral and humoral responses to stress. The signaling through Crhr1 is also associated with cAMP production and ERK1/2 activation, which are important in various physiological processes [1].

In LPS-induced depression-like behavior in mice, the Crhr1 antagonist antalarmin alleviated such behavior, inhibited changes in related protein levels in the hippocampus, and reduced corticosterone levels, indicating that Crhr1 may play a role in depression-like behavior [2]. In stress-induced gut dysbiosis, mice with enhanced CRH-Crhr1 signaling experienced mitochondrial impairment in colonocytes, leading to gut dysbiosis. Inhibiting Crhr1 expression could improve this situation, suggesting Crhr1's role in stress-induced gastrointestinal diseases [3]. Also, in mammalian embryonic neural stem cell development, Crhr1 is required for maintaining neural stem cell properties through the CRHR1/CREB/REST signaling cascade [4].

In conclusion, Crhr1 is essential for stress-related physiological responses, and its dysregulation is associated with various diseases. Gene knockout or conditional knockout mouse models have been used to reveal its role in depression-like behavior, stress-induced gut dysbiosis, and embryonic neural stem cell development. Understanding Crhr1's functions provides insights into the mechanisms of stress-related disorders and potential therapeutic targets.