Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

2013 ◽  
Vol 127 (5) ◽  
pp. 637-641 ◽  
Author(s):  
Michael J. Meaney ◽  
David H. Aitken ◽  
Shari R. Bodnoff ◽  
Linda J. Iny ◽  
Joseph E. Tatarewicz ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Brain Regions ◽  
Postnatal Handling

Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

1985 ◽  
Vol 99 (4) ◽  
pp. 765-770 ◽  
Author(s):  
Michael J. Meaney ◽  
David H. Aitken ◽  
Shari R. Bodnoff ◽  
Linda J. Iny ◽  
Joseph E. Tatarewicz ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Brain Regions ◽  
Postnatal Handling

Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders

2003 ◽  
Vol 15 (6) ◽  
pp. 354-367 ◽  
Author(s):  
Mario F Juruena ◽  
Anthony J Cleare ◽  
Moisés E Bauer ◽  
Carmine M Pariante
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Affective Disorders ◽  
Molecular Mechanisms ◽  
Antidepressant Treatment ◽  
Brain Regions ◽  
Suppression Test ◽  
Treatment Research ◽  
Second Messenger Pathways ◽  
The Impact

Changes in the hypothalamic–pituitary–adrenocortical (HPA) system are characteristic of depression, and in the majority of these patients these result in HPA axis hyperactivity. This is further supported by the reduced sensitivity to the inhibitory effects of the glucocorticoid, dexamethasone (DEX), on the production of adrenocorticotropic hormone (ACTH) and cortisol, during the DEX suppression test and the DEX-corticotropin-releasing hormone (DEX/CRH) test. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GRs in depressed patients. These studies have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRH in various brain regions postulated to be involved in the causality of depression. This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signaling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Hypotheses regarding the mechanism of these receptor changes involve non-steroid compounds that regulate GR function via second messenger pathways, such as cytokines and neurotransmitters. Moreover, we present recent evidence suggesting that membrane steroid transporters such as the multidrug resistance (MDR) p-glycoprotein, which regulate access of glucocorticoids to the brain, could be a fundamental target of antidepressant treatment. Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders.

scholarly journals Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development

2004 ◽  
Vol 181 (1) ◽  
pp. 105-116 ◽  
Author(s):  
HJ Speirs ◽  
RW Brown ◽  
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
In Situ Hybridisation ◽  
Hydroxysteroid Dehydrogenase ◽  
Brain Regions ◽  
Mrna Levels ◽  
Critical Periods ◽  
Organ Systems ◽  
Upper Respiratory

Glucocorticoids play important roles in organ development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed ontogeny in the mouse of the glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type-1 (11beta-HSD1), which amplifies glucocorticoid levels locally; the ontogeny was determined using in situ hybridisation from embryonic day 9.5 (E9.5, term=E19) until after birth. At E9.5 fetal GR mRNA levels are very low, except in fetal placenta. GR gene expression rises during gestation with striking tissue-specific differences in timing and extent. Before E13.5, an increase is clear in gastrointestinal (GI) and upper respiratory tracts, discrete central nervous system (CNS) regions, precartilage and especially in the liver (E10.5-E12). Later, further increases occur in lung, GI and upper respiratory tracts, muscle, pituitary and thymus. In a few tissues such increases are temporary, e.g. ureteric ducts (E13.5-E16.5) and pancreas (E14.5-E16.5, expression later falling sharply). Fetal 11beta-HSD1 mRNA expression is first clearly observed at E14.5-E15, initially in the fetal placenta then in the umbilical cord. Later, 11beta-HSD1 expression is seen as follows: (i) from E15 in lung and liver, rising strongly; (ii) thymus, from E15 (lower level); (iii) at low levels in a few brain regions, including the hippocampus (E16.5+); and (iv) in muscle group fascial planes and tendon insertions. This is the first detailed study of the ontogeny of these two genes and, in combination with previous work on the ontogeny of 11beta-HSD2 and the mineralocorticoid receptor, suggests potential critical periods of glucocorticoid sensitivity during development for several organ systems.

The effects of postnatal handling on the development of the glucocorticoid receptor systems and stress recovery in the rat

1985 ◽  
Vol 9 (5-6) ◽  
pp. 731-734 ◽  
Author(s):  
Michael J. Meaney ◽  
David H. Aitken ◽  
Shari R. Bodnoff ◽  
Linda J. Iny ◽  
Robert M. Sapolsky
Keyword(s):  
Glucocorticoid Receptor ◽  
Stress Recovery ◽  
Postnatal Handling

The CNS site of glucocorticoid negative feedback during LPS- and psychological stress-induced fevers

1996 ◽  
Vol 271 (3) ◽  
pp. R732-R737 ◽  
Author(s):  
L. E. Morrow ◽  
J. L. McClellan ◽  
J. J. Klir ◽  
M. J. Kluger
Keyword(s):  
Glucocorticoid Receptor ◽  
Dentate Gyrus ◽  
Receptor Antagonist ◽  
Open Field ◽  
Psychological Stress ◽  
Negative Feedback ◽  
Brain Regions ◽  
Type Ii ◽  
Neural Connections ◽  
Sites Of Action

Glucocorticoids exert negative feedback in the anterior hypothalamus (AH) during lipopolysaccharide (LPS)-induced fevers, but the central location of their negative feedback during psychological stress-induced fever has not been determined. To confirm that glucocorticoid modulation of LPS fever occurs in the AH, adrenalectomized animals were injected intrahypothalamically with either 0.25 ng of corticosterone or vehicle followed by 50 micrograms/kg LPS intraperitoneally. Animals pretreated with corticosterone developed significantly smaller fevers (P = 0.007) than animals given vehicle. To determine if glucocorticoid modulation during psychological stress-induced fever may occur in the hippocampus, the fornix was transected to block hippocampal communication with the AH. This resulted in significantly larger psychological stress-induced fevers (P = 0.02) compared with sham-operated animals. There were no differences between these groups for LPS-induced fevers (P = 0.92). To determine where in the hippocampus glucocorticoids might exert their negative feedback during psychological stress, rats were microinjected with either 1 ng RU-38486 (a type II glucocorticoid receptor antagonist) or vehicle into the dentate gyrus prior to exposure to the open field. There were no differences between the psychological stress-induced fevers of the RU-38486- and vehicle-injected groups, supporting the hypothesis that these fevers are modulated elsewhere in the hippocampus. Our data support the hypothesis that glucocorticoids modulate LPS-induced fever in the AH and do not involve the hippocampus, and that psychological stress-induced fevers are modulated by neural connections between the hippocampus and the hypothalamus. The precise sites of action of glucocorticoid negative feedback on stress-induced fevers in the hippocampus (or other brain regions) are not yet known.

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