Lunga P, Herbert J
Department of Anatomy, University of Cambridge, Cambridge, UK.
J Neuroendocrinol. 2004 Sep;16(9):776-85. doi: 10.1111/j.1365-2826.2004.01234.x.
Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17beta-oestradiol on hypothalamic-pituitary-adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17beta-oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17beta-oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17beta-oestradiol-treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin-releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17beta-oestradiol treatment at the higher dose (120 microg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17beta-oestradiol-treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17beta-oestradiol-replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non-stressed control rats with or without 17beta-oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17beta-oestradiol-treated rats. After repeated restraint stress, 17beta-oestradiol-replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17beta-oestradiol-treated ovariectomized rats, but stress-induced anxiety behaviour is reduced.
性类固醇在调节反应方面的作用超出了生殖范畴。本研究调查了性类固醇17β - 雌二醇对下丘脑 - 垂体 - 肾上腺（HPA）轴以及对急性或反复束缚应激的行为反应的影响。通过皮下硅橡胶胶囊用17β - 雌二醇或花生油处理的去卵巢大鼠，每天进行处理（无应激）、急性（单次，1小时）或每日（10天，每天1小时）束缚应激。应激结束时采集的血液显示，17β - 雌二醇处理增强了对急性束缚的皮质酮反应。在每日暴露于束缚后，未处理的雌性大鼠的皮质酮反应明显减弱，但与去势未处理的雌性大鼠相比，17β - 雌二醇处理的大鼠仍表现出过度反应。在束缚结束后3小时采集脑组织，使用同位素原位杂交法检测下丘脑室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）和血管加压素基因的表达。高剂量（120微克/毫升）的17β - 雌二醇处理降低了基础CRF mRNA水平。应激导致17β - 雌二醇处理的大鼠中CRF mRNA表达增加，但在载体组中未增加。反复束缚应激导致PVN小细胞血管加压素基因表达增加，在17β - 雌二醇替代的大鼠中更明显。将动物置于高架十字迷宫中5分钟以测试焦虑情况。有无17β - 雌二醇替代的无应激对照大鼠在探索迷宫开放臂上花费的时间百分比相同。先前暴露于急性束缚应激导致探索开放臂所花费的时间显著减少，表明这些大鼠的焦虑水平增加；在载体组和17β - 雌二醇处理的大鼠中均观察到这种效应。反复束缚应激后，17β - 雌二醇替代的大鼠在探索迷宫开放臂上花费的时间与对照组相同，表明适应。相比之下，未替代的大鼠在反复束缚后仍显示开放臂探索显著减少。本研究提供了新的数据，表明在17β - 雌二醇处理的去卵巢大鼠中，HPA轴对反复应激仍有反应，但应激诱导的焦虑行为减少。
