Title:“Stress” is 80 Years Old: From Hans Selye Original Paper in 1936 to Recent Advances in GI Ulceration
VOLUME: 23 ISSUE: 27
Author(s):Sandor Szabo*, Masashi Yoshida, Janos Filakovszky and Gyorgy Juhasz
Affiliation:Department of Pathology, University of California-Irvine Sch. of Med., Irvine, CA 92625, Department of Pathology, University of California-Irvine Sch. of Med., Irvine, CA 92625, Department of Pathology, University of California-Irvine Sch. of Med., Irvine, CA 92625, Department of Pathology, University of California-Irvine Sch. of Med., Irvine, CA 92625
Keywords:Stress, history, distress, eustress, stress triad, gastric and duodenal ulcers, cysteamine, propionitrile, dopamine, MPTP,
Parkinson's disease, angiogenic growth factors, sucralfate, BPC-157.
Abstract:The first scientific publication on ‘general adaption syndrome’, or as we know today ‘biologic stress’
has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that
contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/
stressors, but his idea about a ‘nonspecific bodily response' originated from his observations of sick patients
whom he had seen as a medical student and young clinician. Autopsy of stressed rats revealed three major,
grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as
well as hemorrhagic gastric erosions/ulcers (the “stress triad”). Based on this and additional observations, he
concluded that the key master organ in stress reactions is the adrenal cortex (although he also accepted the limited
and short lasting effect of catecholamines released from the adrenal medulla) which stimulated by an increased
secretion of ACTH, secreted by the anterior pituitary gland. He thus identified the first molecular mediators of the
stress reaction, i.e., steroids released from the adrenal cortex that we call today glucocorticoids, based on his
classification and naming of steroids. At the end of a very productive life in experimental medicine, Selye recognized
that under both unpleasant and demanding stressors as well as positive, rewarding stimuli adrenal cortex
releases the same glucocorticoids and only certain brain structures may distinguish the stimuli under distress and
eustress - terms he introduced in 1974, that also contained his last definition of stress: the nonspecific response of
the body on any demand on it. After brief description of the history of stress research, the rest of this review is
focused on one element of stress triad, i.e., gastroduodenal ulceration, especially its pathogenesis, prevention and
treatment. Following a short description of acute gastroprotection, discovered by one of Selye's students, we
discuss new molecular mediators of gastroduodenal ulceration like dopamine and new drugs that either only heal
(very potently, on molar basis) or prevent and heal ulcers like sucralfate derivatives and the relatively new peptide
BPC-157. We conclude that despite the extensive and multidisciplinary research on stress during the last 80 years,
a lot of basic and clinical research is needed to better understand the manifestations, central and peripheral molecular
regulators of stress response, especially the modes of prevention/management of distress or its transformation
into eustress and the treatment of stress-related diseases.
