STRESS, FEEDBACK AND FACILITATION IN THE HYPOTHALAMOPITUITARY-ADRENAL AXIS
STRESS, FEEDBACK AND FACILITATION IN THE HYPOTHALAMOPITUITARY-ADRENAL AXIS
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DOI：
10.1111/j.1365-2826.1992.tb00200.x
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发表时间：
1992-10-01
影响因子：
3.2
通讯作者：
CASCIO, CS
中科院分区：
文献类型：
--
作者：
DALLMAN, MF;AKANA, SF;CASCIO, CS
很明显，至少20年来，有一个悖论限制了对肾上腺皮质生理学的理解。首先，下丘脑-垂体-肾上腺（HPA）轴似乎对肾上腺分泌的糖皮质激素的反馈抑制非常敏感。其次，应激会导致肾上腺类固醇分泌充足，但似乎不会抑制HPA轴的后续活动。达尔曼和琼斯在20世纪70年代研究了这个问题。我们发现，大鼠持续90分钟的抑制应激并没有抑制皮质酮(B)对随后轻度腹腔注射应激的反应。然而，注射促肾上腺皮质激素（ACTH）或模拟B对抑制反应的B，确实抑制了B对随后注射应激的反应。我们得出的结论是，应力必须诱导下丘脑轴对应力的后续反应的促进作用(1)。我们两人都不满意这种完全演绎的方法。1971年，我们与Vernikos合作，对双侧肾上腺切除术后1至2天的大鼠进行了研究，并进行了ACTH的生物测定，在笔记本上记录了我们失败的尝试，以显示应激性促进的直接证据。结果是无法解释的；我们现在知道，这是由于肾上腺切除术后反馈信号消失后的头几天内HPA轴中枢部分的极度不平衡。
It has been obvious for at least 2 decades that there is a paradox that limits understanding of adrenocortical physiology. First, the hypothalamo-pituitary-adrenal (HPA) axis seems to be very sensitive to feedback inhibition by glucocorticoid hormones secreted from the adrenals. Second, stress, which causes ample adrenal steroid secretion, does not appear to inhibit subsequent activity in the HPA axis.Dallman and Jones worked on this problem in the 1970’s (1). We showed that prolonged restraint stress of 90 min duration in rats did not inhibit the corticosterone (B) response to the subsequent mild stress of intraperitoneal injection. However, injection of adrenocorticotropin (ACTH) or B which mimicked the B response to restraint, did inhibit the B response to subsequent injection stress. We concluded that stress must induce a facilitatory effect on subsequent responses of the HPA axis to stress (1). Neither of us was satisfied with this entirely deductive approach, and in 1971, in collaboration with Vernikos, we filled a notebook with our unsuccessful attempts to show direct evidence for stressinduced facilitation, studying rats 1 to 2 days after bilateral adrenalectomy and bioassay of ACTH. The results were uninterpretable; we know now that this is because of the extreme disequilibrium in central components of the HPA axis that occurs during the first days after adrenalectomy with removal of the feedback signal.