A rapid release of corticosteroid-binding globulin from the liver restrains the glucocorticoid hormone response to acute stress.
A rapid release of corticosteroid-binding globulin from the liver restrains the glucocorticoid hormone response to acute stress.
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DOI：
10.1210/en.2011-1008
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发表时间：
2011-10
期刊：
影响因子：
4.8
通讯作者：
Linthorst AC
中科院分区：
文献类型：
--
作者：
Qian X;Droste SK;Gutièrrez-Mecinas M;Collins A;Kersanté F;Reul JM;Linthorst AC
严格控制糖皮质激素对压力的反应对于健康至关重要。在血液中，糖皮质激素大部分与皮质类固醇结合球蛋白 (CBG) 结合，只有一小部分激素是游离的。只有游离的糖皮质激素才能发挥生物学作用，但对其在应激过程中的调节知之甚少。我们使用双探针体内微透析方法发现，在大鼠中，强迫游泳压力引起的游离皮质酮（其主要糖皮质激素）的升高在血液中以及皮下组织和大脑等目标区室中惊人地相似。然而，在所有区室中，与血液中的总皮质酮反应相比，游离皮质酮反应延迟了 20-30 分钟。我们发现 CBG 是造成这次延误的关键因素。游泳压力会通过肝脏释放蛋白质，引起 CBG 蛋白质和血液中结合能力的快速（5 分钟内）大幅上升。因此，面对循环中总激素水平不断上升，应激后循环 CBG 水平的增加会在约 20 分钟内抑制游离皮质酮浓度的上升。压力引起的 CBG 增加似乎特定于中度和强压力源。束缚压力和强迫游泳都会导致循环CBG增加，而其水平不受轻微新奇压力的影响。我们的数据揭示了 CBG 在急性应激后糖皮质激素生理学调节中的新的、高度动态的作用。
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.
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影响因子：
4.8
作者：
Karssen, AM;Meijer, OC;de Kloet, ER
通讯作者：
de Kloet, ER
影响因子：
4.8
作者：
Klieber, Michael A.;Underhill, Caroline;Muller, Yves A.
通讯作者：
Muller, Yves A.
DOI：
10.1126/science.1168750
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aller SG;Yu J;Ward A;Weng Y;Chittaboina S;Zhuo R;Harrell PM;Trinh YT;Zhang Q;Urbatsch IL;Chang G
通讯作者：
Chang G
影响因子：
4.8
作者：
Droste SK;Collins A;Lightman SL;Linthorst AC;Reul JM
通讯作者：
Reul JM
影响因子：
4
作者：
Breuner, CW;Orchinik, M
通讯作者：
Orchinik, M