ABSTRACT
The hypothalamic-pituitary-adrenal (HPA) axis is central to homeostasis, stress responses, energy metabolism, and neuropsychiatric function. The history of this complex system involves discovery of the relevant glands (adrenal, pituitary, hypothalamus), hormones (cortisol, corticotropin, corticotropin-releasing hormone), and the receptors for these hormones. The adrenal and pituitary were identified by classical anatomists, but most of this history has taken place rather recently, and has involved complex chemistry, biochemistry, genetics, and clinical investigation. The integration of the HPA axis with modern neurology and psychiatry has cemented the role of endocrinology in contemporary studies of behavior.
Subject(s)
Adrenocorticotropic Hormone/metabolism , Corticotropin-Releasing Hormone/metabolism , Endocrinology/history , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , Receptors, Cell Surface/metabolism , Adrenocorticotropic Hormone/history , Animals , Corticotropin-Releasing Hormone/history , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , Humans , Hydrocortisone/history , Receptors, Cell Surface/historyABSTRACT
Selye pioneered the stress concept that is ingrained in the vocabulary of daily life. This was originally build on experimental observations that divers noxious agents can trigger a similar triad of endocrine (adrenal enlargement), immune (involution of thymus) and gut (gastric erosion formation) responses as reported in a letter to Nature in 1936. Subsequently, he articulated the underlying mechanisms and hypothesized the existence of a "first mediator" in the hypothalamus able to orchestrate this bodily changes. However he took two generations to identify this mediator. The Nobel Laureate, Roger Guillemin, a former Selye's PhD student, demonstrated in 1955 the existence of a hypothalamic factor that elicited adrenocorticotropic hormone release from the rat pituitary and named it corticotropin releasing factor (CRF). In 1981, Wylie Vale, a former Guillemin's Ph Student, characterized CRF as 41 amino acid and cloned the CRF1 and CRF2 receptors. This paves the way to experimental studies establishing that the activation of the CRF signaling pathways in the brain plays a key role in mediating the stress-related endocrine, behavioral, autonomic and visceral responses. The unraveling of the biochemical coding of stress is rooted in Selye legacy continues to have increasing impact on the scientific community.
Subject(s)
Corticotropin-Releasing Hormone/history , General Adaptation Syndrome/history , Hypothalamus , Immune System , Peptic Ulcer/history , Pituitary Hormone-Releasing Hormones/history , Stress, Physiological , Thymus Gland , Adrenal Glands/metabolism , Adrenal Glands/pathology , Adrenocorticotropic Hormone/history , Animals , Atrophy , Corticotropin-Releasing Hormone/metabolism , General Adaptation Syndrome/metabolism , General Adaptation Syndrome/pathology , History, 20th Century , Humans , Hypertrophy , Hypothalamus/metabolism , Immune System/metabolism , Peptic Ulcer/etiology , Peptic Ulcer/pathology , Pituitary Hormone-Releasing Hormones/metabolism , Rats , Signal Transduction , Stress, Physiological/immunology , Thymus Gland/metabolism , Thymus Gland/pathologyABSTRACT
The studies reviewed in this article certainly do not constitute the entire body of research conducted by Wylie Vale's group and his collaborators, they might constitute turning points in CRF research. In addition, the studies reviewed here show that, over the course of 31 years (from 1981 to 2012), Wylie tirelessly pursued the answers to fundamental questions regarding CRF. He was a man whose drive never seemed to falter.