Spencer R L, Miller A H, Moday H, Stein M, McEwen B S
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.
Endocrinology. 1993 Nov;133(5):1941-50. doi: 10.1210/endo.133.5.8404640.
To examine diurnal differences in the proportions of receptors that were occupied and activated by basal and stress levels of corticosterone, we measured available type I (mineralocorticoid) and type II (glucocorticoid) adrenal steroid receptor levels in brain, pituitary, and immune tissues of unstressed and acutely stressed rats at the times of day when basal corticosterone secretion was at its trough [morning (AM)] and peak [evening (PM)]. In general, the estimated adrenal steroid receptor activation was greater in brain than in pituitary or immune tissue, and within a particular tissue, there was a greater degree of estimated activation of the adrenal steroid high affinity type I receptor than of the type II receptor. There was a greater activation of brain type II receptors by basal corticosterone in the PM (30-35%) than the AM (5-15%). As acute stress produced similar levels of receptor activation at both times of day (45-50%), the net change in type II receptor activation in the brain after acute stress was much smaller in the PM than in the AM. This suggests that there may be diurnal differences in the role of type II receptors in corticosterone negative feedback on the hypothalamic-pituitary-adrenal axis. In immune tissues, type II receptor activation by acute stress was especially heterogeneous, depending on both the immune compartment and the time of day, suggesting that these are important factors contributing to a differential impact of corticosterone on immune responses during acute stress. Taken together our results suggest that the tonic and phasic influences of corticosterone on target tissue responses very not only with the diurnal and stress secretion patterns of corticosterone, but also with target tissue factors, such as type I and type II receptor expression and hormone bioavailability. All of these factors contribute to considerable selectivity of action for the systemic hormone corticosterone.
为了研究基础水平和应激水平的皮质酮所占据和激活的受体比例的昼夜差异,我们在基础皮质酮分泌处于低谷[上午(AM)]和峰值[晚上(PM)]的一天中的不同时间,测量了未应激和急性应激大鼠的脑、垂体和免疫组织中可用的I型(盐皮质激素)和II型(糖皮质激素)肾上腺类固醇受体水平。一般来说,估计的肾上腺类固醇受体激活在脑中比在垂体或免疫组织中更大,并且在特定组织内,肾上腺类固醇高亲和力I型受体的估计激活程度比II型受体更大。基础皮质酮对脑II型受体的激活在下午(30 - 35%)比上午(5 - 15%)更大。由于急性应激在一天中的两个时间产生相似水平的受体激活(45 - 50%),急性应激后脑中II型受体激活的净变化在下午比上午小得多。这表明II型受体在皮质酮对下丘脑 - 垂体 - 肾上腺轴的负反馈作用中可能存在昼夜差异。在免疫组织中,急性应激对II型受体的激活特别不均匀,这取决于免疫区室和一天中的时间,表明这些是导致皮质酮在急性应激期间对免疫反应产生不同影响的重要因素。综合我们的结果表明,皮质酮对靶组织反应的紧张性和阶段性影响不仅随皮质酮的昼夜和应激分泌模式而变化,还随靶组织因素如I型和II型受体表达以及激素生物利用度而变化。所有这些因素导致全身激素皮质酮具有相当大的作用选择性。