Miyanaga K, Miyabo S, Ooya E
Department of Internal Medicine, Fukui Medical School, Japan.
Endocrinol Jpn. 1990 Feb;37(1):1-7. doi: 10.1507/endocrj1954.37.1.
The effects of chronic (14 day) intracerebroventricular infusion of various amounts of ovine corticotropin-releasing factor (oCRF) on the circadian blood corticosterone rhythm in male rats were examined. Control (saline-infused) rats showed distinct blood corticosterone rhythms over 48 h with nadirs at 0900 h and peaks at 2100 h on days 6-7 and 13-14. oCRF at 3 pmol/h did not affect the circadian corticosterone rhythm on these days. When oCRF was infused at a rate of 12 pmol/h, blood corticosterone was increased throughout the 48 h periods. A significant circadian rhythm remained at days 6-7, but continuous infusion for an additional 7 days disrupted the rhythm. Higher doses of oCRF (48 and 240 pmol/h) obliterated the rhythm during both periods; the disruption was characterized by an increase in corticosterone during the lights-on period without a substantial change in the evening maximum. Thus, the blood corticosterone concentration was eventually confined within a narrow range, not exceeding the normal circadian peak, over a wide dose range of centrally administered CRF. Significant effects of oCRF on body and adrenal weight were observed only at the two highest doses used. These findings may provide some insight into the state of the hypothalamic-pituitary-adrenal axis in animals exposed to chronic stress and in patients with depression.
研究了慢性（14天）脑室内注入不同剂量的绵羊促肾上腺皮质激素释放因子（oCRF）对雄性大鼠昼夜血皮质酮节律的影响。对照（注入生理盐水）大鼠在第6 - 7天和第13 - 14天的48小时内呈现出明显的血皮质酮节律，最低点在0900时，峰值在2100时。下午以3 pmol/h的速率注入oCRF在这些日子里不影响昼夜皮质酮节律。当以12 pmol/h的速率注入oCRF时，在整个48小时期间血皮质酮升高。在第6 - 7天仍存在显著的昼夜节律，但再持续注入7天则扰乱了该节律。更高剂量的oCRF（48和240 pmol/h）在两个时间段均消除了节律；这种扰乱的特征是在光照期皮质酮增加，而傍晚的最大值没有实质性变化。因此，在中枢给予的CRF的广泛剂量范围内，血皮质酮浓度最终被限制在一个狭窄范围内，不超过正常昼夜峰值。仅在使用的两个最高剂量下观察到oCRF对体重和肾上腺重量有显著影响。这些发现可能为暴露于慢性应激的动物和抑郁症患者下丘脑 - 垂体 - 肾上腺轴的状态提供一些见解。
