Age-related changes in hypothalamic-pituitary-adrenal axis activity of male C57BL/6J mice

Publication Type:

Journal Article


Neuroendocrinology, Volume 81, Number 6, p.372-380 (2005)


0028-3835 (Print)0028-38

DOI Name (links to online publication)



Adrenocorticotropic Hormone/blood; Aging/*physiology; Animals; Arginine Vasopressin/biosynthesis; Body Weight/physiology; Circadian Rhythm/physiology; Corticotropin-Releasing Hormone/biosynthesis; Hippocampus/metabolism; Hypothalamo-Hypophyseal System/*gr


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.