Poster Presentation The International Congress of Neuroendocrinology 2014

Exposure to acute stress induces dynamic changes in neuronal corticosteroid-binding globulin in the rat brain (#243)

Xiaoxiao Qian 1 , Mark A. Burton 1 , Matthew C. Towner 1 , Johannes M.H.M. Reul 1 , Astrid C.E. Linthorst 1
  1. University of Bristol, Bristol, United Kingdom

In plasma about 90% of glucocorticoid hormones are bound to corticosteroid-binding globulin (CBG), leaving only 5-10% free and biologically active. Previously we reported that plasma levels of CBG increase rapidly after stress. When rats are forced to swim, CBG levels rise within 5 min and peak at around 30min1. The CBG increase in plasma is caused by release of CBG from the liver1, and precipitates a delayed response of free corticosterone as compared to the stress-induced response in plasma total corticosterone1,2. Although CBG is found in the brain, its regulation and function in this organ are so far unclear. Based on the marked effects of stress on circulating CBG, we investigated whether brain CBG also responds to stress. Using immunohistochemistry and double-immunofluorescence, we found that CBG protein is expressed in the rat hypothalamus and hippocampus. In the hippocampus, CBG-immunoreactivity (CBG-ir) was mainly found in neurons in the hilar region of the dentate gyrus and did not respond to 15-min forced swimming. In the hypothalamus, CBG-ir was found in all sub-regions of the paraventricular nucleus (PVN) and showed co-localisation with vasopressin in about 28% of CBG-ir cells, indicating a potential role of CBG in the regulation of vasopressin-mediated responses to stress. Swimming resulted in a significant decrease in CBG-ir (and vasopressin) in all PVN sub-regions. Studies employing novelty (30 min in a novel cage) and restraint stress (30min in a restrainer) showed that these effects were stressor-dependent. Thus, restraint stress decreased PVN CBG-ir, but no significant effect of novelty was found. Our data demonstrate for the first time that brain CBG is responsive to stress and therefore further underscore its physiological role in coordinating the stress response. These observations are of potential importance for stress-related psychiatric disorders in which glucocorticoid hormone physiology is derailed.

Supported by The Wellcome Trust.

  1. Qian X, Droste SK, Gutièrrez-Mecinas M, Collins A, Kersanté F, Reul JMHM, Linthorst ACE (2011) A rapid release of corticosteroid-binding globulin from the liver restrains the glucocorticoid hormone response to acute stress. Endocrinology 152:3738-3748.
  2. Droste SK, de Groote L, Atkinson HC, Lightman SL, Reul JMHM, Linthorst ACE (2008) Corticosterone levels in the brain show a distinct ultradian rhythm but a delayed response to forced swim stress. Endocrinology 149:3244-3253.