Age-related changes in hypothalamic-pituitary-adrenal axis activity of male C57BL/6J mice.
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.
Dalm
Sergiu
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. s.dalm@lacdr.leidenuniv.nl
Enthoven
Leo
L
Meijer
Onno C
OC
van der Mark
Maaike H
MH
Karssen
Adriaan M
AM
de Kloet
E Ron
ER
Oitzl
Melly S
MS
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000375:Aging / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000096:biosynthesis; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000254:growth & development* / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000254:growth & development* / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone