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Steroids. 2014 Mar;81:109-15. doi: 10.1016/j.steroids.2013.10.013. Epub 2013 Nov 16.

Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain.

Author information

1
INRA, Nutrition & Neurobiologie Intégrée (NutriNeuro), UMR 1286, 33076 Bordeaux, France; Univ Bordeaux, Nutrition & Neurobiologie Intégrée (NutriNeuro), UMR 1286, 33076 Bordeaux, France. Electronic address: mpmoisan@bordeaux.inra.fr.
2
INRA, Nutrition & Neurobiologie Intégrée (NutriNeuro), UMR 1286, 33076 Bordeaux, France; Univ Bordeaux, Nutrition & Neurobiologie Intégrée (NutriNeuro), UMR 1286, 33076 Bordeaux, France.
3
CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), UMR 5287, Universités de Bordeaux1 et 2, 33400 Talence, France; UFR Sciences et Technique, Université de Tours, Parc de Grandmont, 37200 Tours, France.
4
CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), UMR 5287, Universités de Bordeaux1 et 2, 33400 Talence, France.

Abstract

Corticosteroid binding globulin (CBG) is a glycoprotein synthesized in liver and secreted in the blood where it binds with a high affinity but low capacity glucocorticoid hormones, cortisol in humans and corticosterone in laboratory rodents. In mammals, 95% of circulating glucocorticoids are bound to either CBG (80%) or albumin (15%) and only the 5% free fraction is able to enter the brain. During stress, the concentration of glucocorticoids rises significantly and the free fraction increases even more because CBG becomes saturated. However, glucocorticoids unbound to CBG are cleared from the blood more quickly. Our studies on mice totally devoid of CBG (Cbg k.o.) showed that during stress these mutant mice display a lower rise of glucocorticoids than the wild-type controls associated with altered emotional reactivity. These data suggested that CBG played a role in the fast actions of glucocorticoids on behavior. Further analyses demonstrated that stress-induced memory retrieval impairment, an example of the fast action of glucocorticoids on the brain is abolished in the Cbg k.o. mice. This effect of stress on memory retrieval could be restored in the Cbg k.o. mice by infusing corticosterone directly in the hippocampus. The mechanisms explaining these effects involved an increased clearance but no difference in corticosterone production. Thus, CBG seems to have an important role in maintaining in blood a glucocorticoid pool that will be able to access the brain for the fast effects of glucocorticoids.

KEYWORDS:

Brain; Glucocorticoids; Hippocampus; Memory; Stress; Transcortin

PMID:
24252379
DOI:
10.1016/j.steroids.2013.10.013
[Indexed for MEDLINE]
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