Coincident plasma ACTH and corticosterone time series: comparisons between young and old rats

Senescence is accompanied by a reduced ability to respond to a variety of physical and behavioral stressors. A sizable literature has been devoted to the interplay between hypothalamic-pituitary-adrenocortical axis dysfunction and senescence; yet, the precise interactions remain an enigma. Adrenocorticotropic hormone (ACTH) is secreted in pulsatile bursts generating complex signals in the plasma compartment that must be "read" by adrenocortical cells in order to initiate appropriate secretory responses. We have previously demonstrated subtle differences between young and old rats in the pattern of fluctuations in plasma ACTH concentrations over time, despite no difference in mean levels. The present work addressed the physiological significance of these differences in the plasma ACTH signal by analyzing the corresponding plasma corticosterone concentration time series and the relationship between these two hormones over time. Time series of integrated 10-min ACTH and corticosterone concentrations were collected over 4 h at the time of diurnal activation and analyzed in the time and frequency domains. The time of onset of the diurnal surge occurred 20 min later in old rats, and the ratio of corticosterone to ACTH was less at the time of onset and peak of the diurnal surge. Corticosterone levels were lower in old rats and mean ACTH and corticosterone levels were correlated in young but not old rats, as were maximum levels of the two hormones. Cross-correlation of ACTH and corticosterone time series and comparison of spectra were consistent with smoother fluctuations in plasma corticosterone in old animals with less variability at time scales less than 55 min. We conclude that age may be associated with a delay in diurnal activation of the HPA axis, a loss of sensitivity of adrenal corticosterone secretion to plasma ACTH levels, and a relative loss of high frequency variability in the corticosterone signal, as seen in many physiological systems with age.