title: A rapid release of corticosteroid-binding globulin from the liver restrains the glucocorticoid hormone response to acute stress.
abstract: A strict control of glucocorticoid hormone responses to stress is essential for health. In blood, glucocorticoid hormones are for the largest part bound to corticosteroid-binding globulin (CBG), and just a minor fraction of hormone is free. Only free glucocorticoid hormone is able to exert biological effects, but little is known about its regulation during stress. We found, using a dual-probe in vivo microdialysis method, that in rats, the forced-swim stress-induced rise in free corticosterone (its major glucocorticoid hormone) is strikingly similar in the blood and in target compartments such as the subcutaneous tissue and the brain. However, in all compartments, the free corticosterone response was delayed by 20-30 min as compared with the total corticosterone response in the blood. We discovered that CBG is the key player in this delay. Swim stress evoked a fast (within 5 min) and profound rise in CBG protein and binding capacity in the blood through a release of the protein from the liver. Thus, the increase in circulating CBG levels after stress restrains the rise in free corticosterone concentrations for approximately 20 min in the face of mounting total hormone levels in the circulation. The stress-induced increase in CBG seems to be specific for moderate and strong stressors. Both restraint stress and forced swimming caused an increase in circulating CBG, whereas its levels were not affected by mild novelty stress. Our data uncover a new, highly dynamic role for CBG in the regulation of glucocorticoid hormone physiology after acute stress.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Bristol BS1 3NY, United Kingdom.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Qian
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Droste
authors.forename: María
authors.initials: M
authors.lastname: Gutièrrez-Mecinas
authors.forename: Andrew
authors.initials: A
authors.lastname: Collins
authors.forename: Flavie
authors.initials: F
authors.lastname: Kersanté
authors.forename: Johannes M H M
authors.initials: JM
authors.lastname: Reul
authors.forename: Astrid C E
authors.initials: AC
authors.lastname: Linthorst
mesh_terms: D000208:Acute Disease; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism*; D014156:Transcortin / Q000378:metabolism*
chemical_list: D014156:Transcortin; D003345:Corticosterone