Crhr2, short for corticotropin-releasing hormone receptor 2, is a G-protein-coupled receptor. It is involved in the hypothalamic-pituitary-adrenal stress response and has been associated with multiple pathways such as those related to insulin sensitivity, glucose metabolism, angiogenesis, and inflammation [1,2,3]. It also plays a role in emotional and autonomic function regulation [4]. Genetic models, especially knockout mouse models, are valuable for studying its functions.

In male mice, acute dosing of UCN2 (a ligand for CRHR2) induces systemic insulin resistance, while chronic elevation of UCN2 resolves metabolic complications. CRHR2 recruits different proteins depending on UCN2 concentration, and pre-treatment with UCN2 leads to its internalization and affects insulin signaling [1]. Crhr2-/-male mice show enhanced anxious behavior, not due to changes in HPA axis activity but due to impaired responses in specific brain regions as indicated by reduced Creb phosphorylation [4]. In rats, CRHR2 in the nucleus of the solitary tract contributes to intermittent hypoxia-induced hypertension, and down-regulation of CRHR2 in this area may be an adaptive response [5].

In conclusion, Crhr2 is crucial in regulating insulin sensitivity, glucose metabolism, anxiety-related behaviors, and blood pressure. The use of Crhr2 knockout mouse models has significantly contributed to understanding its role in metabolic diseases, mood disorders, and cardiovascular conditions.