The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

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How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

/pdf/protective-and-damaging-effects-of-stress-mediators-34e0m747fy.pdf

Protective and Damaging Effects of Stress Mediators

This meta-analysis reviews 208 laboratory studies of acute psychological stressors and tests a theoretical model delineating conditions capable of eliciting cortisol responses. Psychological stressors increased cortisol levels; however, effects varied widely across tasks. Consistent with the theoretical model, motivated performance tasks elicited cortisol responses if they were uncontrollable or characterized by social-evaluative threat (task performance could be negatively judged by others), when methodological factors and other stressor characteristics were controlled for. Tasks containing both uncontrollable and social-evaluative elements were associated with the largest cortisol and adrenocorticotropin hormone changes and the longest times to recovery. These findings are consistent with the animal literature on the physiological effects of uncontrollable social threat and contradict the belief that cortisol is responsive to all types of stressors.

http://anthro.vancouver.wsu.edu/media/Course_files/anth-260-edward-h-hagen/acute-stressors-and-cortisol-responses-a-theoretical-integration-and-synthesis-of-laboratory-research-1.pdf

Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research.

Part I. From There to Here - Theoretical Background: 1. From visiousness to viciousness: theories of intergroup relations 2. Social dominance theory as a new synthesis Part II. Oppression and its Psycho-Ideological Elements: 3. The psychology of group dominance: social dominance orientation 4. Let's both agree that you're really stupid: the power of consensual ideology Part III. The Circle of Oppression - The Myriad Expressions of Institutional Discrimination: 5. You stay in your part of town and I'll stay in mine: discrimination in the housing and retail markets 6. They're just too lazy to work: discrimination in the labor market 7. They're just mentally and physically unfit: discrimination in education and health care 8. The more of 'them' in prison, the better: institutional terror, social control and the dynamics of the criminal justice system Part IV. Oppression as a Cooperative Game: 9. Social hierarchy and asymmetrical group behavior: social hierarchy and group difference in behavior 10. Sex and power: the intersecting political psychologies of patriarchy and empty-set hierarchy 11. Epilogue.

http://catdir.loc.gov/catdir/samples/cam032/98044356.pdf

Social Dominance: An Intergroup Theory of Social Hierarchy and Oppression

In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Stress and the brain: from adaptation to disease

Glucocorticoids are the principal steroid hormones produced by the inner zones of the adrenal cortex. The natural glucocorticoids, present in amounts which vary according to species, are Cortisol and corticosterone. Corticosterone is generally about half as active as Cortisol. Dexamethasone, prednisolone, triamcinolone acetonide and certain other synthetic analogues of glucocorticoids which are widely used therapeutically and experimentally have some advantages over the natural hormones with regard to both activity and specificity. Dexamethasone, for example, is 10 to 100 times more active than Cortisol, has about 10 times higher affinity for glucocorticoid receptors, and is a ‘purer’ glucocorticoid in the sense that it cross-reacts much less with mineralocorticoid receptors. Cortisone and prednisone, once thought to be glucocorticoids, are now known to have no activity in themselves but to require conversion, respectively, to Cortisol and prednisolone (cf. Munck and Leung, 1977).

Glucocorticoid-induced lymphocyte death

Mechanisms of glucocorticoid-induced immunosuppression: inhibitory effects on expression of Fc receptors and production of T-cell growth factor.

Hormone-induced hyperphosphorylation of specific phosphorylated sites in the mouse glucocorticoid receptor.

Recently a 2- to 3-fold increase in the number of glucocorticoid receptors in human peripheral lymphocytes has been noted after in vitro mitogen stimulation. Here, we extend these observations to in vivo immunization. After unilateral immunization of adrenalectomized male rats, a 50% increase in glucocorticoid receptor sites per cell, determined by binding of dexamethasone, was observed in cell suspensions of homolateral lymph nodes over those from the contralateral nonimmunized side of the same animal. The association constant for dexamethasone was similar in both groups, as was the stereospecificity for various steroids, the time course of cytoplasmic and nuclear association, and cytoplasmic-to-nuclear translocation. Despite a 50% increase in the number of glucocorticoid receptor sites per cell, the cells from the homolateral and controlateral lymph nodes were equally sensitive to the inhibitory effects of dexamethasone, as determined by measurements of the incorporation of radiolabeled precursors of protein, RNA, and DNA, or measurements of in vitro cell survival.

Glucocorticoids and lymphocytes. I. Increased glucocorticoid receptor levels in antigen-stimulated lymphocytes.

Phosphorylation of glucocorticoid receptor-associated and free forms of the approximately 90-kDa heat shock protein before and after receptor activation.

Allan Munck

Papers

Glucocorticoid-induced lymphocyte death

Mechanisms of glucocorticoid-induced immunosuppression: inhibitory effects on expression of Fc receptors and production of T-cell growth factor.

Hormone-induced hyperphosphorylation of specific phosphorylated sites in the mouse glucocorticoid receptor.

Glucocorticoids and lymphocytes. I. Increased glucocorticoid receptor levels in antigen-stimulated lymphocytes.

Phosphorylation of glucocorticoid receptor-associated and free forms of the approximately 90-kDa heat shock protein before and after receptor activation.