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)

/pdf/how-do-glucocorticoids-influence-stress-responses-4egr3fa2k0.pdf

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

Evidence for Irreversible, Actinomycin D-sensitive, and Temperature-sensitive Steps following Binding of Cortisol to Glucocorticoid Receptors and Preceding Effects on Glucose Metabolism in Rat Thymus Cells

Specific glucocorticoid receptors in thymus cells. Localization in the nucleus and extraction of the cortisol-receptor complex.

In an attempt to lay a sound foundation for understanding the therapeutic effectiveness of glucocorticoids in the treatment of hematological cancers, we have studied glucocorticoid receptors and sensitivity to glucocorticoids in vitro in the malignant cells from 56 patients with leukemia and lymphoma and in peripheral lymphocytes from normal donors. In contrast to several previous studies in which myeloblasts and lymphocytes from patients with chronic lymphocytic leukemia were reported to lack glucocorticoid receptors, we have found that with a whole-cell assay there is saturable binding of dexamethasone in all cases, with 400 to 13,230 nuclear binding sites/cell. These binding sites were similar in all respects studied to those of glucocorticoid receptors in the normal lymphocytes and other cell types. Supporting a physiological role for these receptors, normal lymphocytes and cells of 42 of 43 patients tested (including 5 of 5 with acute lymphocytic leukemia, 10 of 10 with chronic lymphocytic leukemia, and 17 of 18 with acute nonlymphocytic leukemia or chronic myelocytic leukemia in blast crisis) showed dose-dependent effects of glucocorticoids in vitro of glucose transport and l-leucine, uridine, or thymidine incorporation. In 38 of 44 cases and in the normal lymphocytes, cell death or impairment of proliferation was noted. Greatest sensitivity was exhibited by cells from patients with acute and chronic lymphocytic leukemia and lymphoma. These results indicate that cells of all hematological cancers have receptors for glucocorticoids and that variations in clinical sensitivity to glucocorticoid therapy are not related to the presence or absence of the receptor as has been proposed previously.

https://cancerres.aacrjournals.org/content/canres/38/11_Part_2/4268.full.pdf

Glucocorticoid Receptors and Sensitivity of Isolated Human Leukemia and Lymphoma Cells

Time Course of Early Events in the Action of Glucocorticoids on Rat Thymus Cells in Vitro: SYNTHESIS AND TURNOVER OF A HYPOTHETICAL CORTISOL-INDUCED PROTEIN INHIBITOR OF GLUCOSE METABOLISM AND OF A PRESUMED RIBONUCLEIC ACID

The glucocorticoid receptor binding capacity of rat thymus cells disappears when the cells are depleted of ATP by anaerobiosis, and rapidly reappears when ATP levels are restored. Loss and recovery of binding capacity occurs even when protein synthesis is suppressed with cycloheximide. In view of this and similar work in other cell systems, we proposed that in cells deprived of ATP the receptor is present in a form--the 'null receptor' form, as we shall call it--that cannot bind hormone. Although many subsequent observations support this idea, no direct evidence has appeared for the existence of the null receptor. We have attempted to detect the null receptor in WEHI-7 mouse thymoma cells with a monoclonal antibody to the glucocorticoid receptor. Here we report that the null receptor is bound in the nuclei of ATP-depleted cells, and is present in amounts comparable to those of receptors in normal cells.

Allan Munck

Papers

Evidence for Irreversible, Actinomycin D-sensitive, and Temperature-sensitive Steps following Binding of Cortisol to Glucocorticoid Receptors and Preceding Effects on Glucose Metabolism in Rat Thymus Cells

Specific glucocorticoid receptors in thymus cells. Localization in the nucleus and extraction of the cortisol-receptor complex.

Glucocorticoid Receptors and Sensitivity of Isolated Human Leukemia and Lymphoma Cells

Time Course of Early Events in the Action of Glucocorticoids on Rat Thymus Cells in Vitro: SYNTHESIS AND TURNOVER OF A HYPOTHETICAL CORTISOL-INDUCED PROTEIN INHIBITOR OF GLUCOSE METABOLISM AND OF A PRESUMED RIBONUCLEIC ACID

Glucocorticoid receptors lacking hormone-binding activity are bound in nuclei of ATP-depleted cells.