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Endocrine Reviews 21 (1): 55-89
Copyright © 2000 by The Endocrine Society

How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions1

Robert M. Sapolsky, L. Michael Romero and Allan U. Munck1

Department of Biological Sciences (R.M.S.), Stanford University, Stanford, California 94305; Department of Biology (L.M.R.), Tufts University, Medford, Massachusetts 02155; and Department of Physiology (A.U.M.), Dartmouth Medical School, Lebanon, New Hampshire 03756

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 stress-response 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.




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J. Exp. Biol.Home page
L. Remage-Healey, D. P. Nowacek, and A. H. Bass
Dolphin foraging sounds suppress calling and elevate stress hormone levels in a prey species, the Gulf toadfish
J. Exp. Biol., November 15, 2006; 209(22): 4444 - 4451.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
A. Nicholas, C. D. Munhoz, D. Ferguson, L. Campbell, and R. Sapolsky
Enhancing Cognition after Stress with Gene Therapy.
J. Neurosci., November 8, 2006; 26(45): 11637 - 11643.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
E. K. Adam, L. C. Hawkley, B. M. Kudielka, and J. T. Cacioppo
Day-to-day dynamics of experience-cortisol associations in a population-based sample of older adults
PNAS, November 7, 2006; 103(45): 17058 - 17063.
[Abstract] [Full Text] [PDF]


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Proc R Soc BHome page
B. J Heidinger, I. C.T Nisbet, and E. D Ketterson
Older parents are less responsive to a stressor in a long-lived seabird: a mechanism for increased reproductive performance with age?
Proc R Soc B, September 7, 2006; 273(1598): 2227 - 2231.
[Abstract] [Full Text] [PDF]


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J EndocrinolHome page
D S Gardner, B W M Van Bon, J Dandrea, P J Goddard, S F May, V Wilson, T Stephenson, and M E Symonds
Effect of periconceptional undernutrition and gender on hypothalamic-pituitary-adrenal axis function in young adult sheep.
J. Endocrinol., August 1, 2006; 190(2): 203 - 212.
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J EndocrinolHome page
E. Roggero, A. R Perez, M. Tamae-Kakazu, I. Piazzon, I. Nepomnaschy, H. O Besedovsky, O. A Bottasso, and A. del Rey
Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection.
J. Endocrinol., August 1, 2006; 190(2): 495 - 503.
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J EndocrinolHome page
E. H Stolte, B M L. V. van Kemenade, H. F J Savelkoul, and G. Flik
Evolution of glucocorticoid receptors with different glucocorticoid sensitivity.
J. Endocrinol., July 1, 2006; 190(1): 17 - 28.
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J. Clin. Endocrinol. Metab.Home page
W. Arlt, F. Hammer, P. Sanning, S. K. Butcher, J. M. Lord, B. Allolio, D. Annane, and P. M. Stewart
Dissociation of Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate in Septic Shock
J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2548 - 2554.
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J. Neurosci.Home page
R. Malcher-Lopes, S. Di, V. S. Marcheselli, F.-J. Weng, C. T. Stuart, N. G. Bazan, and J. G. Tasker
Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release.
J. Neurosci., June 14, 2006; 26(24): 6643 - 6650.
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J. Neurophysiol.Home page
J. T. King, P. V. Lovell, M. Rishniw, M. I. Kotlikoff, M. L. Zeeman, and D. P. McCobb
beta2 and beta4 Subunits of BK Channels Confer Differential Sensitivity to Acute Modulation by Steroid Hormones
J Neurophysiol, May 1, 2006; 95(5): 2878 - 2888.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
A. E. Coutinho, J. E. Campbell, S. Fediuc, and M. C. Riddell
Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11beta-HSD1 in the Syrian hamster
J Appl Physiol, May 1, 2006; 100(5): 1483 - 1488.
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J ANIM SCIHome page
J. A. Carroll, E. L. Berg, T. A. Strauch, M. P. Roberts, and H. G. Kattesh
Hormonal profiles, behavioral responses, and short-term growth performance after castration of pigs at three, six, nine, or twelve days of age
J Anim Sci, May 1, 2006; 84(5): 1271 - 1278.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. Nierop, A. Bratsikas, A. Klinkenberg, U. M. Nater, R. Zimmermann, and U. Ehlert
Prolonged Salivary Cortisol Recovery in Second-Trimester Pregnant Women and Attenuated Salivary {alpha}-Amylase Responses to Psychosocial Stress in Human Pregnancy
J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1329 - 1335.
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EndocrinologyHome page
N. Aluru and M. M. Vijayan
Aryl Hydrocarbon Receptor Activation Impairs Cortisol Response to Stress in Rainbow Trout by Disrupting the Rate-Limiting Steps in Steroidogenesis
Endocrinology, April 1, 2006; 147(4): 1895 - 1903.
[Abstract] [Full Text] [PDF]


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J. Physiol.Home page
A. Kapoor, E. Dunn, A. Kostaki, M. H. Andrews, and S. G. Matthews
Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids
J. Physiol., April 1, 2006; 572(1): 31 - 44.
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Proc R Soc BHome page
A. A Carlson, M. B Manser, A. J Young, A. F Russell, N. R Jordan, A. S McNeilly, and T. Clutton-Brock
Cortisol levels are positively associated with pup-feeding rates in male meerkats
Proc R Soc B, March 7, 2006; 273(1586): 571 - 577.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
R. Campos-Rodriguez, A. Quintanar-Stephano, R. A. Jarillo-Luna, G. Oliver-Aguillon, J. Ventura-Juarez, V. Rivera-Aguilar, I. Berczi, and K. Kovacs
Hypophysectomy and Neurointermediate Pituitary Lobectomy Reduce Serum Immunoglobulin M (IgM) and IgG and Intestinal IgA Responses to Salmonella enterica Serovar Typhimurium Infection in Rats
Infect. Immun., March 1, 2006; 74(3): 1883 - 1889.
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Proc R Soc BHome page
A. S Kitaysky, E. V Kitaiskaia, J. F Piatt, and J. C Wingfield
A mechanistic link between chick diet and decline in seabirds?
Proc R Soc B, February 22, 2006; 273(1585): 445 - 450.
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Eur J EndocrinolHome page
K. M Oltmanns, B. Dodt, B. Schultes, H. H Raspe, U. Schweiger, J. Born, H. L Fehm, and A. Peters
Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients
Eur. J. Endocrinol., February 1, 2006; 154(2): 325 - 331.
[Abstract] [Full Text] [PDF]




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