Viau V, Sharma S, Meaney M J
Developmental Neuroendocrinology Laboratory, Douglas Hospital Research Center, Montreal, Canada.
J Neuroendocrinol. 1996 Jan;8(1):1-8. doi: 10.1111/j.1365-2826.1996.tb00680.x.
Pituitary-adrenal responses to stress in the neonatal rat have been reported to be substantially reduced compared to older animals (i.e. a stress hyporesponsive period). This supposed period of endocrine quiescence is characterized by reduced stress-induced increases in both plasma ACTH and corticosterone. At the same time a number of authors have noted the decreased plasma corticosteroid-binding globulin (CBG) levels of the neonate, and there is evidence for an increased percentage of free corticosterone as well as age-related changes in the volume of distribution for corticosterone. These findings suggest that the reduced CBG levels might enhance the biological significance of existing glucocorticoid levels, beyond that assumed on the basis of plasma total corticosterone levels. We examined this question by estimating hippocampal glucocorticoid receptor occupancy and 'translocation' in Day 6, Day 15, and adult animals under basal and stressful conditions. The results showed that: 1) plasma ACTH levels were elevated in Day 6 animals in response to acute exposure to ether, maternal separation, and maternal separation + ether, however, ACTH responses were substantially lower than in Day 15 or adult animals; 2) Plasma total corticosterone levels followed a similar pattern; most noteworthy was the potent glucocorticoid response in Day 15 animals to the combination of maternal separation + ether; 3) Plasma CBG levels in Day 6 animals were extremely low (< 3% adult values); by Day 15 CBG levels were about 25% of adult levels. Interestingly, maternal separation was associated with a substantial decrease in plasma CBG levels; 4) Hippocampal glucocorticoid receptor occupancy/translocation was similar at all ages under both basal and stress conditions. The only notable exception occurred during maternal separation in Day 15 animals, where the percentage of hippocampal glucocorticoid receptor occupancy/translocation was higher than that observed at any time in either Day 6 or adult animals. This finding is likely related to the decrease in plasma CBG that occurs following separation of Day 15 pups from the dam. Thus, despite the higher corticosterone level in the adult, the increase in glucocorticoid receptor occupancy/translocation was generally comparable across all ages either under basal conditions, or following stress. These receptor data underscore the importance of developmental changes in plasma CBG levels.
据报道，与成年动物相比，新生大鼠垂体 - 肾上腺对应激的反应显著降低（即应激低反应期）。这个假定的内分泌静止期的特征是应激诱导的血浆促肾上腺皮质激素（ACTH）和皮质酮增加减少。同时，一些作者注意到新生儿血浆皮质类固醇结合球蛋白（CBG）水平降低，并且有证据表明游离皮质酮的百分比增加以及皮质酮分布容积的年龄相关变化。这些发现表明，CBG水平降低可能会增强现有糖皮质激素水平的生物学意义，超出基于血浆总皮质酮水平所假设的范围。我们通过估计第6天、第15天和成年动物在基础和应激条件下海马糖皮质激素受体占有率和“易位”来研究这个问题。结果表明：1）第6天的动物在急性暴露于乙醚、母婴分离以及母婴分离 + 乙醚后，血浆ACTH水平升高，然而，ACTH反应明显低于第15天或成年动物；2）血浆总皮质酮水平遵循类似模式；最值得注意的是第15天的动物对母婴分离 + 乙醚组合有强烈的糖皮质激素反应；3）第6天动物的血浆CBG水平极低（< 成年值的3%）；到第15天，CBG水平约为成年水平的25%。有趣的是，母婴分离与血浆CBG水平的大幅降低有关；4）在基础和应激条件下，所有年龄段的海马糖皮质激素受体占有率/易位情况相似。唯一显著的例外发生在第15天动物的母婴分离期间，此时海马糖皮质激素受体占有率/易位的百分比高于第6天或成年动物在任何时候观察到的情况。这一发现可能与第15天幼崽与母鼠分离后血浆CBG的降低有关。因此，尽管成年动物的皮质酮水平较高，但在基础条件下或应激后，糖皮质激素受体占有率/易位的增加在所有年龄段通常是可比的。这些受体数据强调了血浆CBG水平发育变化的重要性。
