Genetic models and epidemiological studies have contributed to our understanding of the pathophysiology of stress-related disorders. Corticotropin-releasing hormone (CRH) belongs to the family of the so-called CRH related peptides along with Urocortin, Urocortin II (or Stresscopin Related Peptide) and Urocortin III (or Stresscopin). CRH is the major stimulus for pituitary ACTH secretion in humans and plays a major role in the physiologic response to stress. CRH and its receptors (type 1 and 2) are widely distributed throughout the central nervous system and to a lesser extent in peripheral tissues. The receptor distribution in the CNS exhibits a wide inter-species variability. The CRH neurons modulate autonomic and limbic system function. CRH affects a wide array of cardiovascular, metabolic and behavioral effects. The regional actions of this peptide in the CNS and in the periphery are varied and only partially understood. Aberrant CRH action is implicated in psychiatric disorders including depression and anxiety. Data from transgenic mice lacking over expressing CRH and pre-clinical studies involving CRH antagonist administration to Rhesus monkeys have substantiated this theory. Although not yet available for routine clinical use, preliminary proofs of concept studies involving orally administered CRH antagonists to humans are encouraging. The development of selective non-peptide CRH receptor antagonists remains a challenge. Moreover, testing in randomized clinical trials is much needed and will shed new light into the field.
Corticotropin-releasing factor; Urocortin; Antagonist; Receptor; Depression; Anxiety
