Max Planck Institute of Psychiatry, Research Group of Psychoneuroendocrinology, Kraepelinstrasse 2-10, 80804 Munich, Germany Institut National de la Recherche Agronomique (INRA), Laboratory of Nutrition and Integrative Neurobiology, UMR 1286, 146 Rue Leo Saignat, 33076 Bordeaux, France University of Bordeaux, Laboratory of Nutrition and Integrative Neurobiology, UMR 1286, 146 Rue Leo Saignat, 33076 Bordeaux, France.
J Endocrinol. 2013 Oct 28;219(3):217-29. doi: 10.1530/JOE-13-0255. Print 2013 Dec.
Increasing evidence indicates an important role of steroid-binding proteins in endocrine functions, including hypothalamic-pituitary-adrenal (HPA) axis activity and regulation, as they influence bioavailability, local delivery, and cellular signal transduction of steroid hormones. In the plasma, glucocorticoids (GCs) are mainly bound to the corticosteroid-binding globulin (CBG) and to a lesser extend to albumin. Plasma CBG levels are therefore involved in the adaptive stress response, as they determine the concentration of free, biologically active GCs. In this study, we investigated whether male mice with a genetic predisposition for high-reactivity (HR), intermediate-reactivity (IR), or low-reactivity (LR) stress-induced corticosterone (CORT) secretion present different levels of free CORT and CORT-binding proteins, basally and in response to stressors of different intensity. Our results suggest a fine control interaction between plasma CBG expression and stress-induced CORT release. Although plasma CBG levels, and therefore CBG binding capacity, were higher in HR animals, CORT secretion overloaded the CBG buffering function in response to stressors, resulting in clearly higher free CORT levels in HR compared with IR and LR mice (HR>IR>LR), resembling the pattern of total CORT increase in all three lines. Both stressors, restraint or forced swimming, did not evoke fast CBG release from the liver into the bloodstream and therefore CBG binding capacity was not altered in our three mouse lines. Thus, we confirm CBG functions in maintaining a dynamic equilibrium between CBG-bound and unbound CORT, but could not verify its role in delaying the rise of plasma free CORT immediately after stress exposure.
越来越多的证据表明，甾体结合蛋白在包括下丘脑-垂体-肾上腺 (HPA) 轴活动和调节在内的内分泌功能中发挥着重要作用，因为它们影响甾体激素的生物利用度、局部递送和细胞信号转导。在血浆中，糖皮质激素 (GCs) 主要与皮质类固醇结合球蛋白 (CBG) 结合，在较小程度上与白蛋白结合。因此，血浆 CBG 水平参与适应性应激反应，因为它们决定了游离、具有生物活性的 GCs 的浓度。在这项研究中，我们研究了具有高反应性 (HR)、中反应性 (IR) 或低反应性 (LR) 应激诱导皮质酮 (CORT) 分泌遗传倾向的雄性小鼠是否具有不同水平的游离 CORT 和 CORT 结合蛋白，无论是在基础状态还是在不同强度应激源的刺激下。我们的结果表明，血浆 CBG 表达和应激诱导的 CORT 释放之间存在精细的控制相互作用。尽管 HR 动物的血浆 CBG 水平（因此 CBG 结合能力）较高，但 CORT 分泌使 CBG 缓冲功能超负荷，导致 HR 小鼠的游离 CORT 水平明显高于 IR 和 LR 小鼠（HR>IR>LR），类似于所有三种品系的总 CORT 增加模式。两种应激源，束缚或强迫游泳，都没有引起 CBG 从肝脏快速释放到血液中，因此我们的三种小鼠品系中 CBG 结合能力没有改变。因此，我们证实了 CBG 在维持 CBG 结合和未结合 CORT 之间的动态平衡中的作用，但不能证实其在应激暴露后立即延迟血浆游离 CORT 升高的作用。
