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*Substance via MeSH
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*Brain Diseases
Endocrine Reviews 19 (3): 269-301
Copyright © 1998 by The Endocrine Society

Brain Corticosteroid Receptor Balance in Health and Disease1

E. Ronald de Kloet, Erno Vreugdenhil, Melly S. Oitzl and Marian Joëls

Division of Medical Pharmacology (E.R.D.K., E.V., M.S.O.), Leiden/Amsterdam Center for Drug Research, University of Leiden, 2300 RA Leiden, The Netherlands; and Institute for Neurobiology (M.J.), University of Amsterdam, 1098 SM Amsterdam, The Netherlands

I. Introduction
II. Corticosteroid Receptor Properties
A. Corticosteroid receptor diversity in brain and pituitary
B. Access of corticosteroids to brain receptors
C. Expression of MR, GR, and receptor variants
D. Regulation of transcriptional activity
E. Conclusion
III. Molecular and Cellular Effects of Corticosteroids in Hippocampus
A. Intrinsic cell properties
B. Amino acid transmission
C. Aminergic transmission
D. Chronic absence of corticosterone
E. Chronic exposure to high corticosteroid levels
F. Conclusion
IV. Role of Corticosteroid Receptors in the Central Stress Response
A. Corticosteroid receptors and HPA control
B. Role of hippocampus in HPA regulation
C. Behavioral effects involving hippocampal MR and GR
D. Glucocorticoid feedback resistance and supersensitivity
E. GR knockouts
F. Conclusion
V. Implications for Age- and Stress-Related Brain Disorders
A. Role of genotype
B. Impact of early life experience
C. Corticosteroids and affective disorders
D. Aging, neurodegeneration, and age-related diseases
E. Conclusion
VI. Summary




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M. P. Boyle, B. J. Kolber, S. K. Vogt, D. F. Wozniak, and L. J. Muglia
Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness
J. Neurosci., February 15, 2006; 26(7): 1971 - 1978.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Berger, D. P. Wolfer, O. Selbach, H. Alter, G. Erdmann, H. M. Reichardt, A. N. Chepkova, H. Welzl, H. L. Haas, H.-P. Lipp, et al.
Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity
PNAS, January 3, 2006; 103(1): 195 - 200.
[Abstract] [Full Text] [PDF]

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 International Journal of ToxicologyHome page
T. Pung, B. Klein, D. Blodgett, B. Jortner, and M. Ehrich
Examination of Concurrent Exposure to Repeated Stress and Chlorpyrifos on Cholinergic, Glutamatergic, and Monoamine Neurotransmitter Systems in Rat Forebrain Regions
International Journal of Toxicology, January 1, 2006; 25(1): 65 - 80.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. M. Karssen, O. C. Meijer, A. Berry, R. Sanjuan Pinol, and E. R. de Kloet
Low Doses of Dexamethasone Can Produce a Hypocorticosteroid State in the Brain
Endocrinology, December 1, 2005; 146(12): 5587 - 5595.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
I. C. G. Weaver, F. A. Champagne, S. E. Brown, S. Dymov, S. Sharma, M. J. Meaney, and M. Szyf
Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life
J. Neurosci., November 23, 2005; 25(47): 11045 - 11054.
[Abstract] [Full Text] [PDF]

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 J. Neurophysiol.Home page
H. Karst and M. Joels
Corticosterone Slowly Enhances Miniature Excitatory Postsynaptic Current Amplitude in Mice CA1 Hippocampal Cells
J Neurophysiol, November 1, 2005; 94(5): 3479 - 3486.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Park, O. Chan, Q. Li, M. Kiraly, S. G. Matthews, M. Vranic, and M. C. Riddell
Changes in basal hypothalamo-pituitary-adrenal activity during exercise training are centrally mediated
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1360 - R1371.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Zschocke, N. Bayatti, A. M. Clement, H. Witan, M. Figiel, J. Engele, and C. Behl
Differential Promotion of Glutamate Transporter Expression and Function by Glucocorticoids in Astrocytes from Various Brain Regions
J. Biol. Chem., October 14, 2005; 280(41): 34924 - 34932.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Giordano, M. Bo, M. Pellegrino, M. Vezzari, M. Baldi, A. Picu, M. Balbo, L. Bonelli, G. Migliaretti, E. Ghigo, et al.
Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade
J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5656 - 5662.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
G. M. Kalabis, A. Kostaki, M. H. Andrews, S. Petropoulos, W. Gibb, and S. G. Matthews
Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection
Biol Reprod, October 1, 2005; 73(4): 591 - 597.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
L. Pascual-Le Tallec and M. Lombes
The Mineralocorticoid Receptor: A Journey Exploring Its Diversity and Specificity of Action
Mol. Endocrinol., September 1, 2005; 19(9): 2211 - 2221.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
K. A. Fenoglio, K. L. Brunson, S. Avishai-Eliner, B. A. Stone, B. J. Kapadia, and T. Z. Baram
Enduring, Handling-Evoked Enhancement of Hippocampal Memory Function and Glucocorticoid Receptor Expression Involves Activation of the Corticotropin-Releasing Factor Type 1 Receptor
Endocrinology, September 1, 2005; 146(9): 4090 - 4096.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. J. Cerqueira, J. M. Pego, R. Taipa, J. M. Bessa, O. F. X. Almeida, and N. Sousa
Morphological Correlates of Corticosteroid-Induced Changes in Prefrontal Cortex-Dependent Behaviors
J. Neurosci., August 24, 2005; 25(34): 7792 - 7800.
[Abstract] [Full Text] [PDF]

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 PediatricsHome page
G. A. Lodygensky, K. Rademaker, S. Zimine, M. Gex-Fabry, A. F. Lieftink, F. Lazeyras, F. Groenendaal, L. S. de Vries, and P. S. Huppi
Structural and Functional Brain Development After Hydrocortisone Treatment for Neonatal Chronic Lung Disease
Pediatrics, July 1, 2005; 116(1): 1 - 7.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. Chung, G. H. Son, S. H. Park, E. Park, K. H. Lee, D. Geum, and K. Kim
Differential Adaptive Responses to Chronic Stress of Maternally Stressed Male Mice Offspring
Endocrinology, July 1, 2005; 146(7): 3202 - 3210.
[Abstract] [Full Text] [PDF]

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 PediatricsHome page
J. J. Volpe
Encephalopathy of Prematurity Includes Neuronal Abnormalities
Pediatrics, July 1, 2005; 116(1): 221 - 225.
[Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
O. Chan, K. Inouye, E. M. Akirav, E. Park, M. C. Riddell, S. G. Matthews, and M. Vranic
Hyperglycemia does not increase basal hypothalamo-pituitary-adrenal activity in diabetes but it does impair the HPA response to insulin-induced hypoglycemia
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R235 - R246.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
S. Ridder, S. Chourbaji, R. Hellweg, A. Urani, C. Zacher, W. Schmid, M. Zink, H. Hortnagl, H. Flor, F. A. Henn, et al.
Mice with Genetically Altered Glucocorticoid Receptor Expression Show Altered Sensitivity for Stress-Induced Depressive Reactions
J. Neurosci., June 29, 2005; 25(26): 6243 - 6250.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
S Hesketh, D S Jessop, S Hogg, and M S Harbuz
Differential actions of acute and chronic citalopram on the rodent hypothalamic-pituitary-adrenal axis response to acute restraint stress
J. Endocrinol., June 1, 2005; 185(3): 373 - 382.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
X. Wang and D. B. DeFranco
Alternative Effects of the Ubiquitin-Proteasome Pathway on Glucocorticoid Receptor Down-Regulation and Transactivation Are Mediated by CHIP, an E3 Ligase
Mol. Endocrinol., June 1, 2005; 19(6): 1474 - 1482.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
T. W. W. Pace and R. L. Spencer
Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor
Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1082 - E1088.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
L. Pascual-Le Tallec, F. Simone, S. Viengchareun, G. Meduri, M. J. Thirman, and M. Lombes
The Elongation Factor ELL (Eleven-Nineteen Lysine-Rich Leukemia) Is a Selective Coregulator for Steroid Receptor Functions
Mol. Endocrinol., May 1, 2005; 19(5): 1158 - 1169.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
D. P. Merke, J. N. Giedd, M. F. Keil, S. L. Mehlinger, E. A. Wiggs, S. Holzer, E. Rawson, A. C. Vaituzis, C. A. Stratakis, and G. P. Chrousos
Children Experience Cognitive Decline Despite Reversal of Brain Atrophy One Year After Resolution of Cushing Syndrome
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2531 - 2536.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
R. G. Smith, L. Betancourt, and Y. Sun
Molecular Endocrinology and Physiology of the Aging Central Nervous System
Endocr. Rev., April 1, 2005; 26(2): 203 - 250.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
S. Kuhlmann, M. Piel, and O. T. Wolf
Impaired Memory Retrieval after Psychosocial Stress in Healthy Young Men
J. Neurosci., March 16, 2005; 25(11): 2977 - 2982.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
O. C. Meijer, B. Topic, P. J. Steenbergen, G. Jocham, J. P. Huston, and M. S. Oitzl
Correlations between Hypothalamus-Pituitary-Adrenal Axis Parameters Depend on Age and Learning Capacity
Endocrinology, March 1, 2005; 146(3): 1372 - 1381.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
O. C. Meijer, E. Kalkhoven, S. van der Laan, P. J. Steenbergen, S. H. Houtman, T. F. Dijkmans, D. Pearce, and E. R. de Kloet
Steroid Receptor Coactivator-1 Splice Variants Differentially Affect Corticosteroid Receptor Signaling
Endocrinology, March 1, 2005; 146(3): 1438 - 1448.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. Schmidt, S. Levine, M. S. Oitzl, M. van der Mark, M. B. Muller, F. Holsboer, and E. R. de Kloet
Glucocorticoid Receptor Blockade Disinhibits Pituitary-Adrenal Activity during the Stress Hyporesponsive Period of the Mouse
Endocrinology, March 1, 2005; 146(3): 1458 - 1464.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
O. Chan, K. Inouye, E. Akirav, E. Park, M. C. Riddell, M. Vranic, and S. G. Matthews
Insulin Alone Increases Hypothalamo-Pituitary-Adrenal Activity, and Diabetes Lowers Peak Stress Responses
Endocrinology, March 1, 2005; 146(3): 1382 - 1390.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
K. E. Inouye, O. Chan, J. T. Y. Yue, S. G. Matthews, and M. Vranic
Effects of diabetes and recurrent hypoglycemia on the regulation of the sympathoadrenal system and hypothalamo-pituitary-adrenal axis
Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E422 - E429.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M. P. Boyle, J. A. Brewer, M. Funatsu, D. F. Wozniak, J. Z. Tsien, Y. Izumi, and L. J. Muglia
Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior
PNAS, January 11, 2005; 102(2): 473 - 478.
[Abstract] [Full Text] [PDF]

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 NeuroscientistHome page
I. Glezer and S. Rivest
Glucocorticoids: Protectors of the Brain during Innate Immune Responses
Neuroscientist, December 1, 2004; 10(6): 538 - 552.
[Abstract] [PDF]

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 Arch Gen PsychiatryHome page
H. Jahn, M. Schick, F. Kiefer, M. Kellner, A. Yassouridis, and K. Wiedemann
Metyrapone as Additive Treatment in Major Depression: A Double-blind and Placebo-Controlled Trial
Arch Gen Psychiatry, December 1, 2004; 61(12): 1235 - 1244.
[Abstract] [Full Text] [PDF]

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 Learn. Mem.Home page
S. Gais and J. Born
Declarative memory consolidation: Mechanisms acting during human sleep
Learn. Mem., November 1, 2004; 11(6): 679 - 685.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. Wellhoener, J. Born, H. L. Fehm, and C. Dodt
Elevated Resting and Exercise-Induced Cortisol Levels after Mineralocorticoid Receptor Blockade with Canrenoate in Healthy Humans
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5048 - 5052.
[Abstract] [Full Text] [PDF]


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