Corticotropin-releasing factor (CRF), also known as corticotropin-releasing hormone (CRH), is a peptide hormone and neurotransmitter produced primarily in the hypothalamus, a region of the brain involved in the regulation of various physiological processes, including stress responses, reproduction, and energy balance.
CRF plays a crucial role in the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is the body’s primary stress response system. When the brain perceives a stressor, CRF is released from the hypothalamus into the portal blood system, which connects the hypothalamus with the anterior pituitary gland. Upon reaching the anterior pituitary, CRF stimulates the release of adrenocorticotropic hormone (ACTH) into the bloodstream. ACTH then travels to the adrenal glands, located on top of the kidneys, and stimulates the production and release of cortisol, a glucocorticoid hormone that helps the body cope with stress by increasing blood sugar levels, suppressing the immune system, and modulating metabolism.
Apart from its role in the HPA axis, CRF also functions as a neurotransmitter in various brain regions, where it is involved in the regulation of mood, anxiety, appetite, and energy homeostasis. Dysregulation of CRF signaling has been implicated in several psychiatric and neurological disorders, including depression, anxiety, eating disorders, and addiction. As a result, CRF and its receptors have been considered as potential therapeutic targets for the development of drugs to treat these conditions.
There are two main types of CRF receptors, CRF1 and CRF2, which are both G protein-coupled receptors (GPCRs) and are expressed in different brain regions and peripheral tissues. While the activation of CRF1 receptors is mainly associated with the stress response and the development of anxiety- and depression-like behaviors, the activation of CRF2 receptors has been linked to the regulation of feeding, social behavior, and stress recovery. Therefore, the development of selective CRF receptor agonists or antagonists may hold promise for the treatment of stress-related disorders and other conditions involving CRF signaling.