HISTORICAL PERSPECTIVES

the hypothalamus plays a primary role in the regulation of the pituitary-adrenocortical axis. Subsequently, during the 1950s, Guillemin and Rosenberg, and Saffran and Schally independently observed the presence of a factor in hypo-thalamic extracts (termed corticotropin-releasing factor, CRF) that could stimulate the release of adrenocortico-tropic hormone (ACTH, corticotropin) from anterior pi-tuitary cells in vitro. Although CRF was the first hypotha-lamic hypophysiotropic factor to be recognized, its chemical identity remained elusive until 1981, when Wylie Vale and colleagues at the Salk Institute reported the isolation, characterization, synthesis, and in vitro and in vivo biological activities of a 41-amino acid hypothalamic ovine CRF (1). Just over a decade later, Vale and col-leagues were the first to report the cloning of the human CRF1 receptor from a single human Cushing’s cortico-tropic adenoma using an expression cloning techniques (2). This initial discovery led to the identification of a second receptor subtype (termed CRF2), which has now been localized and characterized in a variety of species (see the following). This chapter provides an overview of the CRF system and its related receptor targets. More detailed and compre-hensive information on CRF is available in recent reviews (3,4) and books (5,6) on the topic