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

Introduction and Background Modern glucocorticoid endocrinology is a colorful, richly varied, but formless discipline—a profusion of cellular, physiological and pharmacological effects, seemingly unrelated through any central hormonal function. A current list of glucocorticoid effects might include such disparate items as stimulation of hepatic gluconeogenesis, inhibition of glucose uptake by peripheral tissues, suppression of inflammation, enhanced excretion of a water load, induction in various cells of tryptophan oxygenase and glutamine synthetase, suppression of numerous immune reactions, inhibition of secretion of several hormones and neuropeptides, and inhibition of activity of plasminogen activator and other neutral proteinases. Judging from recent writings on glucocorticoid physiology, an item that might be low on the list or missing altogether is “increased resistance to stress”.

Physiological Functions of Glucocorticoids in Stress and Their Relation to Pharmacological Actions

To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine.

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T cell growth factor receptors. Quantitation, specificity, and biological relevance

http://www.jbc.org/content/243/21/5556.full.pdf

Allan Munck

Papers

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

Physiological Functions of Glucocorticoids in Stress and Their Relation to Pharmacological Actions

T cell growth factor receptors. Quantitation, specificity, and biological relevance

Specific and Nonspecific Physicochemical Interactions of Glucocorticoids and Related Steroids with Rat Thymus Cells in Vitro

Mouse Glucocorticoid Receptor Phosphorylation Status Influences Multiple Functions of the Receptor Protein