Plasma transcortin influences endocrine and behavioral stress responses in mice.
Endocrinology. 2010-02-01; 151(2): 649-659
DOI: 10.1210/en.2009-0862
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1. Endocrinology. 2010 Feb;151(2):649-59. doi: 10.1210/en.2009-0862. Epub 2009 Dec
18.
Plasma transcortin influences endocrine and behavioral stress responses in mice.
Richard EM(1), Helbling JC, Tridon C, Desmedt A, Minni AM, Cador M, Pourtau L,
Konsman JP, Mormède P, Moisan MP.
Author information:
(1)Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche
1286 PsyNuGen, Universite de Bordeaux 2, F-33076 Bordeaux, France.
Glucocorticoids are released after hypothalamus-pituitary-adrenal axis
stimulation by stress and act both in the periphery and in the brain to bring
about adaptive responses that are essential for life. Dysregulation of the stress
response can precipitate psychiatric diseases, in particular depression. Recent
genetic studies have suggested that the glucocorticoid carrier transcortin, also
called corticosteroid-binding globulin (CBG), may have an important role in
stress response. We have investigated the effect of partial or total transcortin
deficiency using transcortin knockout mice on hypothalamus-pituitary-adrenal axis
functioning and regulation as well as on behaviors linked to anxiety and
depression traits in animals. We show that CBG deficiency in mice results in
markedly reduced total circulating corticosterone at rest and in response to
stress. Interestingly, free corticosterone concentrations are normal at rest but
present a reduced surge after stress in transcortin-deficient mice. No
differences were detected between transcortin-deficient mice for anxiety-related
traits. However, transcortin-deficient mice display increased immobility in the
forced-swimming test and markedly enhanced learned helplessness after prolonged
uncontrollable stress. The latter is associated with an approximately 30%
decrease in circulating levels of free corticosterone as well as reduced Egr-1
mRNA expression in hippocampus in CBG-deficient mice. Additionally,
transcortin-deficient mice show no sensitization to cocaine-induced locomotor
responses, a well described corticosterone-dependent test. Thus, transcortin
deficiency leads to insufficient glucocorticoid signaling and altered behavioral
responses after stress. These findings uncover the critical role of plasma
transcortin in providing an adequate endocrine and behavioral response to stress.
DOI: 10.1210/en.2009-0862
PMID: 20022933 [Indexed for MEDLINE]