CRH-binding Protein: A Regulator of CRH in Stress

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DESCRIPTION (provided by applicant): Anxiety disorders and depression are among the most common psychiatric disorders. The etiology of these conditions is unknown, but exposure to stress and an inability to cope with stress likely contribute to the development of these disorders. Dysregulation of the corticotropin-releasing hormone (CRH) system is associated with depression and certain anxiety disorders, making it a likely candidate for linking stress to these disorders. CRH and its receptors are known to play a role in mediating the stress response. Recent work suggests that CRH-binding protein (CRH-BP) may also play a role in stress. Evidence suggests that CRH-BP binds locally released CRH and prevents its action at CRH receptors. CRH-BP may thus serve to maintain homeostasis in the CRH system, thereby limiting the stress response. Despite this, CRH-BP remains a poorly understood component of the CRH system. The proposed research will focus on the nature of the interactions of CRH-BP with CRH and CRH receptors within the brain during stress. An examination of the stress-induced regulation and function of CRH-BP may prove useful in understanding mechanisms underlying stress-related psychopathology and may lead to new treatment approaches for disorders involving dysregulation of the CRH system.