Corticotropin-releasing hormone. Biology and therapeutic opportunities

Simple Summary: Early neuroendocrine studies on corticotropin-releasing hormone (CRH), or corticotropin-releasing factor (CRF), werefocusedoninvestigatingitsroleinregulatingthehypothalamicpituitary–adrenal axis. In the following years, the characterization of CRH receptors and the availability of specific CRH agonists and antagonists have provided evidence that CRH plays a role in the regulation of several biological systems, as well as in reproduction, neuropsychiatric, gastrointestinal, and immunedisorders and in the development of tumors. Further elucidation of the physiology of CRHwill facilitate characterization of its role in human pathophysiology and exploit the potential of ligands for CRH receptors as novel therapeutic targets. Abstract: In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with high potency and intrinsic activity stimulating the secretion of adrenocorticotropic hormone and-endorphin by cultured anterior pituitary cells. With its sequence known, this neuropeptide was determined to be a hormone and consequently named corticotropin-releasing hormone (CRH), although the term corticotropin-releasing factor (CRF) is still used and preferred in some circumstances. Several decades have passed since this seminal contribution that opened a new research era, expanding the understanding of the coding of stress-related processes. The characterization of CRH receptors, the availability of CRH agonists and antagonists, and advanced immunocytochemical staining techniques have provided evidence that CRH plays a role in the regulation of several biological systems. The purpose of this review is to summarize the present knowledge of this 41-amino-acid peptide.