Novel regulators of the in vitro release of hypothalamic corticotrophin-releasing hormone two decades after its discovery: a review.

Corticotrophin-releasing hormone (CRH) is a 41 amino-acid peptide which was isolated and characterised exactly two decades ago (1). It is distributed heterogeneously throughout the central nervous system (CNS) (2) and, due both to its ability to stimulate the release of adrenocorticotrophic hormone (ACTH) from the pituitary and to its numerous extra-hypophyseal biological effects, is now considered one of the major neuropeptides involved in adaptive processes: CRH indeed coordinates the neuroendocrine, behavioural, autonomic and immune responses to stressors (3-5). The recent cloning of specific CRH receptors (6-8) has further facilitated research on CRH in physiology and in the development of neuropsychiatric diseases, including depression, anxiety and eating disorders. For this reason, and thanks to the availability of specific antagonists and laboratory animal models (such as transgenic mice), CRH is still a peptide under active investigation 20 years after its discovery (9). While CRH-containing neurons are widely distributed within the CNS, the hypothalamic paraventricular nucleus (PVN) is the principal