Meaney M J, Aitken D H, Sharma S, Viau V
Developmental Neuroendocrinology Laboratory, Douglas Hospital-McGill University Research Institute, Montreal, Canada.
Neuroendocrinology. 1992 Feb;55(2):204-13. doi: 10.1159/000126116.
Basal corticosterone (B) levels increase with age in the rat, a result of decreased negative-feedback inhibition of hypothalamic-pituitary-adrenal (HPA) activity. Postnatal handling increases CNS negative-feedback sensitivity and appears to attenuate some of the changes occurring in the HPA axis in later life. In the experiments described here, we have examined basal HPA function in young (6-8 months) and old (22 months), handled (H) and nonhandled (NH) rats in relation to changes in corticosteroid receptor binding. Among young animals, there were no group differences in basal adrenocorticotropin (ACTH) or B levels at any point in the diurnal cycle. In contrast, plasma ACTH and B levels during the PM phase were significantly higher in old NH animals in comparison to old H animals and to both groups of young animals. The H and NH groups did not differ in in vivo adrenal responsiveness to exogenous ACTH. As expected, ACTH sensitivity was greater in all groups during the PM phase and in general, old animals showed a greater response to ACTH regardless of the treatment group. There were no differences across the groups in AM plasma corticosterone-binding globulin (CBG) levels. However, during the PM phase of the cycle, CBG levels were significantly lower and the percentage of B in the free form was significantly higher in the old NH animals. As expected, levels of free B during the PM phase of the cycle were significantly higher in the old NH animals. Thus, there is a significant increase in the PM corticoid signal in the old NH animals that occurs as a function of elevated B and decreased CBG levels; these age-related changes in basal HPA activity were not seen in the old H animals. Type I (mineralocorticoid-like) receptor binding in the hippocampus did not differ as a function of handling and was significantly reduced with age in both H and NH animals. Type II (glucocorticoid) receptor binding decreased as a function of age in both H and NH animals, but was consistently higher in the H animals. There were no differences in type II receptor binding in the hypothalamus or pituitary as a function of age or handling. These data suggest that the increase in basal HPA activity occurring in aged rats is largely restricted to the dark phase of the cycle and is attenuated by postnatal handling, a treatment that increases hippocampal type II corticosteroid receptor binding.
大鼠的基础皮质酮（B）水平随年龄增长而升高，这是下丘脑 - 垂体 - 肾上腺（HPA）活动的负反馈抑制减弱的结果。出生后处理可增加中枢神经系统的负反馈敏感性，并似乎能减弱HPA轴在后期生活中发生的一些变化。在本文所述的实验中，我们研究了年轻（6 - 8个月）和年老（22个月）、经过处理（H）和未经过处理（NH）的大鼠的基础HPA功能与皮质类固醇受体结合变化的关系。在年轻动物中，昼夜周期中任何时间点的基础促肾上腺皮质激素（ACTH）或B水平在各实验组之间均无差异。相比之下，与年老H组动物以及两组年轻动物相比，年老NH组动物在下午阶段的血浆ACTH和B水平显著更高。H组和NH组对外源性ACTH的体内肾上腺反应性没有差异。正如预期的那样，所有组在下午阶段对ACTH的敏感性更高，并且总体而言，年老动物无论治疗组如何，对ACTH的反应都更大。上午血浆皮质酮结合球蛋白（CBG）水平在各实验组之间没有差异。然而，在周期的下午阶段，年老NH组动物的CBG水平显著降低，游离形式的B百分比显著更高。正如预期的那样，年老NH组动物在周期下午阶段的游离B水平显著更高。因此，年老NH组动物下午的皮质激素信号显著增加，这是由于B升高和CBG水平降低所致；在年老H组动物中未观察到这些与年龄相关的基础HPA活动变化。海马体中I型（盐皮质激素样）受体结合在处理方面没有差异，并且在H组和NH组动物中均随年龄显著降低。II型（糖皮质激素）受体结合在H组和NH组动物中均随年龄降低，但在H组动物中始终更高。下丘脑或垂体中II型受体结合在年龄或处理方面没有差异。这些数据表明，老年大鼠基础HPA活动的增加主要局限于周期的黑暗阶段，并且通过出生后处理而减弱，出生后处理这种方法可增加海马体II型皮质类固醇受体结合。
