Dalm Sergiu, Enthoven Leo, Meijer Onno C, van der Mark Maaike H, Karssen Adriaan M, de Kloet E Ron, Oitzl Melly S
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, Einsteinweg 55, NL-2300 RA Leiden, The Netherlands.
Neuroendocrinology. 2005;81(6):372-80. doi: 10.1159/000089555. Epub 2005 Nov 4.
As there is little known about age-related changes in the hypothalamic-pituitary-adrenal (HPA) axis of mice, we determined the daily patterns of corticosterone secretion every 2 h, together with adrenocorticotropic hormone (ACTH) release and central HPA axis markers in the morning and evening of 3-, 9- and 16-month-old male C57BL/6J mice. We observed that: (i) corticosterone secretion showed a distinct age-related circadian pattern. During the light period this was expressed by relative hypercorticism in 9-month-old mice and relative hypocorticism in 16-month-old mice. ACTH was elevated at 16 months of age; (ii) mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA expression in the hippocampus was significantly decreased in 9-month-old mice, whereas in 16-month-old mice, expression was similar to young animals. Circadian variation was modest in all age groups; (iii) the parvocellular hypothalamic paraventricular nucleus (PVN) expressed very high vasopressin mRNA, which was subject to circadian variation in 3- and 9-month-old mice. Furthermore, significant levels of MR mRNA were expressed in the PVN. In conclusion, basal HPA axis activity and expression of its central regulatory markers are age-dependent in mice. This suggests that the capacity to adjust to environmental demands is either a function of age, or depends on different dynamics of the HPA axis.
由于对小鼠下丘脑 - 垂体 - 肾上腺（HPA）轴与年龄相关的变化了解甚少，我们测定了3个月、9个月和16个月大的雄性C57BL/6J小鼠在早晨和晚上每2小时皮质酮分泌的日常模式，以及促肾上腺皮质激素（ACTH）释放和中枢HPA轴标志物。我们观察到：（i）皮质酮分泌呈现出明显的与年龄相关的昼夜节律模式。在光照期，9个月大的小鼠表现为相对高皮质醇血症，16个月大的小鼠表现为相对低皮质醇血症。ACTH在16个月龄时升高；（ii）9个月大的小鼠海马中盐皮质激素（MR）和糖皮质激素受体（GR）mRNA表达显著降低，而16个月大的小鼠，其表达与年轻动物相似。所有年龄组的昼夜变化都较小；（iii）下丘脑室旁核小细胞部（PVN）表达非常高的血管加压素mRNA，在3个月和9个月大的小鼠中其存在昼夜变化。此外，PVN中表达了显著水平的MR mRNA。总之，小鼠的基础HPA轴活性及其中枢调节标志物的表达是年龄依赖性的。这表明适应环境需求的能力要么是年龄的函数，要么取决于HPA轴的不同动态变化。
