Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain.
Steroids. 2014-03-01; 81: 109-115
DOI: 10.1016/j.steroids.2013.10.013
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Moisan MP(1), Minni AM(2), Dominguez G(3), Helbling JC(2), Foury A(2), Henkous N(4), Dorey R(4), Béracochéa D(4).
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: .
(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.
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.