The general adaptation syndrome and the diseases of adaptation

Selye, Hans

doi:10.1016/0021-8707(46)90148-7

Cited by 191 publications

(200 citation statements)

References 72 publications

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“…Although there are some positive influences, stressors result in many harmful actions to the stressed bodies such as the disrupted reproductive system. The stress response is comprised of the physiological adjustments made to compensate for the stressor and preserve balance of the internal milieu of the body [5]. An over abundance of glucocorticoid activity is the hallmark of stress [4].…”

Section: Stress and Leydig Cell Functionmentioning

confidence: 99%

Rapid mechanisms of glucocorticoid signaling in the Leydig cell☆

Lian

Lin

et al. 2008

Steroids

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Stress-mediated elevations in circulating glucocorticoid levels lead to corresponding rapid declines in testosterone production by Leydig cells in the testis. In previous studies we have established that glucocorticoids act on Leydig cells directly, through the classic glucocorticoid receptor (GR), and that access to the GR is controlled prior to the GR by a metabolizing pathway mediated by the type 1 isoform of 11β-hydroxysteroid dehydrogenase (11βHSD1). This enzyme is bidirectional (with both oxidase and reductase activities) and in the rat testis is exclusively localized in Leydig cells where it is abundantly expressed and may catalyze the oxidative inactivation of glucocorticoids. The predominant reductase direction of 11βHSD1 activity in liver cells is determined by an enzyme, hexose-6-phosphate dehydrogenase (H6PDH), on the luminal side of the smooth endoplasmic reticulum (SER). Generation of the pyridine nucleotide cofactor NADPH by H6PDH stimulates the reductase direction of 11βHSD1 resulting in increased levels of active glucocorticoids in liver cells. Unlike liver cells, steroidogenic enzymes including 17β-hydroxysteroid dehydrogenase 3 (17βHSD3) forms the coupling with 11βHSD1. Thus the physiological concentrations of androstenedione serve as a substrate for 17βHSD3 utilizing NADPH to generate NADP+, which drives 11βHSD1 in Leydig cells primarily as an oxidase; thus eliminating the adverse effects of glucocorticoids on testosterone production. At the same time 11βHSD1 generates NADPH which promotes testosterone biosynthesis by stimulating 17βHSD3 in a cooperative cycle. This enzymatic coupling constitutes a rapid mechanism for modulating glucocorticoid control of testosterone biosynthesis. Under stress conditions, glucocorticoids also have rapid actions to suppress cAMP formation thus to lower testosterone production.

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Section: Stress and Leydig Cell Functionmentioning

confidence: 99%

Rapid mechanisms of glucocorticoid signaling in the Leydig cell☆

Lian

Lin

et al. 2008

Steroids

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“…This was first documented by Selye in rats, when he described the chronologic development of the nonspecific response to stressors when their action is prolonged. He termed this the GAS (Selye, 1936(Selye, , 1951(Selye, , 1955(Selye, , 1976, which involved a triphasic response: (i) the alarm reaction, in which adaptation has not yet been acquired; (ii) the stage of resistance, in which adaptation is optimum; and (iii) the stage of exhaustion, in which the acquired adaptation is lost (Selye, 1955). Selye subsequently described diseases of adaptation, including psychosomatic diseases as well as immunologic and inflammatory diseases, which depended primarily on excessive or inappropriate responses to stressors, where an essentially useful defensive reaction (e.g., HPA axis activation or emotional arousal in preparation for fight) can be the major cause of disease if the defense is inappropriate under the circumstances (Selye, 1976).…”

Section: Stress Dysregulation In Neuroactive Steroids: Implications Fmentioning

confidence: 99%

Neurosteroids in the context of stress: Implications for depressive disorders

Girdler

Klatzkin

2007

Pharmacology & Therapeutics

130

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Animal models indicate that the neuroactive steroids 3α,5α-THP (allopregnanolone) and 3α,5α-THDOC (allotetrahydroDOC) are stress responsive, serving as homeostatic mechanisms in restoring normal GABAergic and hypothalamic-pituitary-adrenal (HPA) function following stress. While neurosteroid increases to stress are adaptive in the short term, animal models of chronic stress and depression find lower brain and plasma neurosteroid concentrations and alterations in neurosteroid responses to acute stressors. It has been suggested that disruption in this homeostatic mechanism may play a pathogenic role in some psychiatric disorders related to stress. In humans, neurosteroid depletion is consistently documented in patients with current depression and may reflect their greater chronic stress. Women with the depressive disorder, premenstrual dysphoric disorder (PMDD), have greater daily stress and a greater rate of traumatic stress. While results on baseline concentrations of neuroactive steroids in PMDD are mixed, PMDD women have diminished functional sensitivity of GABA A receptors and our laboratory has found blunted allopregnanolone responses to mental stress relative to non-PMDD controls. Similarly, euthymic women with histories of clinical depression, which may represent a large proportion of PMDD women, show more severe dysphoric mood symptoms and blunted allopregnanolone responses to stress versus never-depressed women. It is suggested that failure to mount an appropriate allopregnanolone response to stress may reflect the price of repeated biological adaptations to the increased life stress that is well documented in depressive disorders and altered allopregnanolone stress responsivity may also contribute to the dysregulation seen in HPA axis function in depression.

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“…There has been a lot of interest in stress since the groundbreaking work by Selye (1946). A considerable amount of research has focused on the body's general adaptation to acute and chronic stress, especially the effect of stress on the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, and immunity, as well as various psychological and social parameters (Sternberg et al, 1989a, b;van de Langerijt et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Psychological Stress can Trigger Atopic Dermatitis in NC/Nga Mice: An Inhibitory Effect of Corticotropin-Releasing Factor

Amano

Negishi

Akiyama

et al. 2007

Neuropsychopharmacol

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Atopic dermatitis (AD) is one of the most common inflammatory diseases of the skin and is usually associated with a family history of atopic diathesis. It has been well established that many environmental or psychological factors aggravate AD. However, it is not clear whether psychological stress by itself can trigger AD. We examined the effect of psychological stress on the onset of AD, using an animal model, the NC/Nga mouse. The animals were exposed to the water avoidance stress (WAS) test to induce psychological stress. Additionally, we examined how corticotropin-releasing factor (CRF) affected the development of AD induced by psychological stress. Under specific pathogen-free (SPF) conditions, NC/Nga mice did not develop AD-like skin lesions. In contrast, NC/Nga mice exposed to psychological stress developed AD-like skin lesions along with elevated levels of serum immunoglobulin E even when kept under SPF conditions. The AD-like skin lesions induced by WAS were completely blocked by pretreating the animals with CRF. Our data indicate that a psychological factor is capable of eliciting AD-like skin lesions in NC/Nga mice. It is possible that the inhibitory effect of CRF may be mediated by the functional modification of various cells that have CRF receptors.

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The general adaptation syndrome and the diseases of adaptation

Cited by 191 publications

References 72 publications

Rapid mechanisms of glucocorticoid signaling in the Leydig cell☆

Rapid mechanisms of glucocorticoid signaling in the Leydig cell☆

Neurosteroids in the context of stress: Implications for depressive disorders

Psychological Stress can Trigger Atopic Dermatitis in NC/Nga Mice: An Inhibitory Effect of Corticotropin-Releasing Factor

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