Hypothalamic Control of Adrenocorticotropin Secretion: Advances since the Discovery of 41-Residue Corticotropin-Releasing Factor

Abstract

IN THE 25 yrs after the first demonstration of CRF in hypothalamic tissue (1, 2), research on CRF progressed along two major lines of experimentation. In the context of a functional anatomical approach, researchers sought to elucidate the hypothalamic organization of neurons that produce CRF and control the secretion of ACTH (for reviews see Refs. 3–5). The second major trend was the quest for the isolation and chemical characterization of the hypothalamic CRF principle (for reviews see Refs. 6–8). It was the discovery of 41-amino acid residue CRF (CRF-41) by Vale and co-workers (9) which provided the missing link between the two major paths of investigation. Aided by decades of expertise accumulated in laboratories throughout the world, workers finally having the right stuff at hand rapidly established CRF-41 as a major physiological mediator of the hypothalamic control of ACTH secretion (for reviews see Refs. 10–12). However, it soon became evident that CRF-41 is not the sole hypothalamic neurohormone involved in the control of pituitary ACTH secretion (e.g. see Refs. 13–17). Thus, the second phase of CRF research, the post-CRF-41 era, had begun.