Martí O, Harbuz M S, Andrés R, Lightman S L, Armario A
Unitat de Fisiologia Animal, Facultat de Ciències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Brain Res. 1999 Mar 6;821(1):1-7. doi: 10.1016/s0006-8993(98)01212-8.
The influence of chronic stress on the status of the hypothalamo-pituitary-adrenal (HPA) axis of sham-operated and adrenalectomised rats was assessed. Animals underwent bilateral adrenalectomy (ADX) and 3 days later they were either left undisturbed or subjected daily to immobilization for 2 h each morning for 14 days (chronic IMO). In situ hybridization histochemistry revealed that ADX increased corticotropin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus (PVN) and proopiomelanocortin (POMC) mRNA levels in the anterior pituitary, in both control and chronically stressed rats as measured on the day following the last exposure to stress. Chronic IMO increased CRF mRNA levels in the PVN and POMC mRNA levels in the anterior pituitary of sham-operated rats, as measured on the day following the last exposure to stress. Chronic IMO potentiated the increase in CRF mRNA in the PVN following ADX and resulted in further increases in CRF mRNA above levels seen in adrenal-intact animals. Finally, chronic stress, while not altering basal ACTH levels of ADX rats, reduced the ACTH response of these animals to a novel stressor (tail-shock for 30 min). These results suggest that chronic stress exerts a stimulatory influence at the hypothalamic level that is partially restrained by daily stress-induced glucocorticoid release. Despite the potentiation by chronic stress of CRF mRNA content in the PVN of ADX rats, a blunted circulating ACTH response to an acute short-term stressor was apparent in ADX-chronically stressed rats, suggesting that chronic stress might also alter POMC processing and/or ACTH secretory patterns in the anterior pituitary in ADX animals.
评估了慢性应激对假手术和肾上腺切除大鼠下丘脑 - 垂体 - 肾上腺（HPA）轴状态的影响。动物接受双侧肾上腺切除术（ADX），3天后，它们要么不做处理，要么每天上午固定2小时，持续14天（慢性固定，chronic IMO）。原位杂交组织化学显示，在最后一次应激暴露后的第二天测量发现，无论是对照大鼠还是长期应激大鼠，ADX均增加了下丘脑室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）的mRNA水平以及垂体前叶中阿黑皮素原（POMC）的mRNA水平。在最后一次应激暴露后的第二天测量发现，慢性固定增加了假手术大鼠PVN中CRF的mRNA水平以及垂体前叶中POMC的mRNA水平。慢性固定增强了ADX后PVN中CRF mRNA的增加，并导致CRF mRNA水平进一步高于肾上腺完整动物的水平。最后，慢性应激虽然没有改变ADX大鼠的基础促肾上腺皮质激素（ACTH）水平，但降低了这些动物对新应激源（30分钟尾部电击）的ACTH反应。这些结果表明，慢性应激在下丘脑水平发挥刺激作用，而这种作用部分受到每日应激诱导的糖皮质激素释放的抑制。尽管慢性应激增强了ADX大鼠PVN中CRF mRNA的含量，但在ADX - 慢性应激大鼠中，对急性短期应激源的循环ACTH反应明显减弱，这表明慢性应激也可能改变ADX动物垂体前叶中POMC的加工和/或ACTH的分泌模式。
