FEEDBACK AND FACILITATION IN THE ADRENOCORTICAL SYSTEM - UNMASKING FACILITATION BY PARTIAL INHIBITION OF THE GLUCOCORTICOID RESPONSE TO PRIOR STRESS
FEEDBACK AND FACILITATION IN THE ADRENOCORTICAL SYSTEM - UNMASKING FACILITATION BY PARTIAL INHIBITION OF THE GLUCOCORTICOID RESPONSE TO PRIOR STRESS
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DOI：
10.1210/en.131.1.57
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发表时间：
1992-07-01
期刊：
影响因子：
4.8
通讯作者：
WALKER, CD
中科院分区：
文献类型：
--
作者：
AKANA, SF;DALLMAN, MF;WALKER, CD
先前强调动物仍然响应于随后的应激源，尽管分泌足够的皮质类固醇信号在第一个压力，这应该起到阻尼响应第二个压力。我们以前假设，压力的行为，以促进随后的反应，在肾上腺皮质系统，这种便利是平衡的皮质类固醇反馈信号。为了直接验证这一假设，我们用氰酮（CK）处理年轻雄性大鼠，以部分阻断肾上腺合成皮质酮（B）的能力。随后，CK-或车辆（VEH）-治疗组的大鼠暴露于第一个应力的30分钟限制与小的血液样本收集在0，15，和30分钟。第一个应力的大鼠亚组12，9，6，或3小时前关灯（12小时）或开灯（24小时）。在12或24小时，再次用0分钟（“基础”）和30分钟（第二次应激）的血样束缚大鼠。当实验组接受第二次压力时，控制组接受第一次压力。测定血浆ACTH和B浓度。虽然在没有应激的情况下，与VEH处理的大鼠相比，CK处理的大鼠的基础B浓度在一天中是正常的，但与VEH处理的组相比，CK处理的大鼠对FIRST应激的B反应降低了60%。当第一个应力期间进行的时间的灯光，“基础”血浆ACTH升高CK组在12小时（熄灯）相比，在先前强调VEH组和未强调CK对照组的水平。在一天中的这个时间，CK大鼠对第二次应激的ACTH反应的幅度与接受其唯一应激的CK大鼠（对照组）或接受第二次应激的VEH处理的大鼠相比没有差异。当第一个应力期间进行的熄灯时间，“基础”血浆ACTH在24小时（灯）在CK和VEH大鼠没有不同的水平相比，在各自的非应激控制。ACTH对第二次应激的反应在24 h时在所有先前应激的CK组中均升高，与CK对照组或VEH组相比。在一天中的任何时间，VEH大鼠的第二次应激ACTH浓度与对照VEH大鼠的浓度均无差异。在12小时（关灯），但不是在24小时（开灯），“基础”ACTH显着升高VEH大鼠以上的非应激VEH控制值。我们从这些实验中得出结论：1）在至少12小时的时间内，先前的应激诱导肾上腺皮质系统的中枢神经成分的易化痕迹，导致在熄灯时对昼夜输入的ACTH反应升高; 2）由于VEH组在所有时间对应激反应正常，因此由FIRST应激施加的易化信号被同时分泌的皮质类固醇反馈信号平衡，因此，重复的应激刺激引起类似幅度的重复ACTH分泌; 3）在CK组中观察到的应激诱导的易化迹线位于位于最后的下丘脑神经内分泌神经元之前的神经部位，因为ACTH对束缚应激的反应仅在开灯时易化，而在关灯时不易化。结果表明，应激诱导的促进随后刺激的ACTH分泌解释了哺乳动物肾上腺皮质系统对重复应激的持续正常反应性。
Previously stressed animals remain responsive to subsequent stressors, despite secreting an adequate corticosteroid signal during the first stress which should act to damp the response to a second stress. We have previously postulated that stress acts to facilitate subsequent responses in the adrenocortical system, and that this facilitation is balanced by the corticosteroid feedback signal. To test this hypothesis directly, we treated young male rats with cyanoketone (CK) to partially block the adrenal capacity to synthesize corticosterone (B). Subsequently, groups of CK- or vehicle (VEH)-treated rats were exposed to the FIRST stress of 30-min restraint with small blood samples collected at 0, 15, and 30 min. The FIRST stress was given to subgroups of rats 12, 9, 6, or 3 h before lights off (12 h) or lights on (24 h). At 12 or 24 h, rats were again restrained with blood samples at 0 ("basal") and 30 min (SECOND stress). Control groups were stressed for the first time when the experimental groups received their SECOND stress. Plasma ACTH and B concentrations were measured. Although in the absence of stress, basal B concentrations were normal in CK-treated compared to VEH-treated rats throughout the day, the B response to the FIRST stress was reduced by 60% in the CK- compared to the VEH-treated group. When the FIRST stress was performed during the time of lights on, "basal" plasma ACTH was elevated in CK groups at 12 h (lights off) compared to levels in both previously stressed VEH groups and unstressed CK controls. There was no difference at this time of day in the magnitude of the ACTH response to the SECOND stress in CK rats compared to that in CK rats receiving their only stress (controls) or that in VEH-treated rats receiving the SECOND stress. When first stress was performed during the time of lights off, "basal" plasma ACTH at 24 h (lights on) in CK and VEH rats were not different compared to levels in their respective unstressed controls. The ACTH response to the SECOND stress at 24 h was elevated in all previously stressed CK groups compared to that in either CK control or VEH groups. At neither time of day were SECOND stress ACTH concentrations in VEH rats different from those in control VEH rats. At 12 h (lights off), but not at 24 h (lights on), "basal" ACTH was significantly elevated in VEH rats above the unstressed VEH control values. We conclude from these experiments that 1) during at least a 12-h period, prior stress induces a facilitatory trace in central neural components of the adrenocortical system that causes an elevated ACTH response to the diurnal input at lights off; 2) because VEH groups were normoresponsive to stress at all times, the facilitatory signal imposed by the FIRST stress is balanced by the simultaneously secreted corticosteroid feedback signal, so that repeated stressors provoke repeated ACTH secretion of similar magnitude; 3) the stress-induced facilitatory trace observed in CK groups resides at a neural site that lies before the final hypothalamic neuroendocrine neurons, because the ACTH response to restraint stress was facilitated only at lights on, not at lights off. The results show that stress-induced facilitation of subsequently stimulated ACTH secretion explains the persistant normoresponsiveness of the mammalian adrenocortical system to repeated stress.