The diurnal secretion of ACTH and corticosterone was examined in chronically cannulated young (3-4 months old), middle-aged (10-12 months old), and old (22-24 months old) Fischer 344 male rats. Plasma corticosterone in young rats increased from baseline concentrations of 78 +/- 5 to a maximum of 171 +/- 24 ng/ml at 1730 h and declined to basal levels by 1930 h. Middle-aged and old rats demonstrated a similar magnitude and time course of corticosterone release. However, comparison of the relative concentrations of ACTH released during the diurnal surge revealed that old rats secreted 35% less ACTH than young or middle-aged animals (P less than 0.05). Age-related changes in the sensitivity of the adrenal gland to a submaximal dose of ACTH were tested in dexamethasone-pretreated animals at 1100 and 1700 h in a separate experiment. Plasma corticosterone levels were significantly greater after ACTH administration (1 mIU/kg ACTHAR, iv) at 1700 h in both young and old rats compared to 1100 h values (P less than 0.05), and levels 20 min post-ACTH injection at 1700 h were significantly greater in old than young or middle-aged rats at the same time (P less than 0.05). These results demonstrate that 1) there are no age-related changes in the diurnal secretion of corticosterone in Fischer 344 male rats; 2) there is a decline in the peak level of ACTH during the diurnal surge of old compared to young animals; and 3) adrenal sensitivity to ACTH at 1700 h is greater in old compared to young or middle-aged rats. We hypothesize that the greater increase in adrenal sensitivity to ACTH is responsible for the maintenance of the corticosterone rhythm in the presence of diminished ACTH concentrations in older rats.

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The effects of long‐term chronic stress during prepubertal periods of growth and development on an organism's ability to release ACTH during future episodes of an acute novel stress and in response to exogenous CRH were examined. Following a 6‐week stress period, in which prepubertal male and female WKY rats were subjected to three different and randomly given stress paradigms (heat, noise and immobilization) at various times of the day (in order to prevent adaptation to stress), chronically stressed male rats were far less able to respond to CRH plus a novel ether stress than were their male controls or their female counterparts. Although baseline ACTH levels were similar in both male and female control and experimental rats, when subjected to a subsequent acute ether stress, the differences in ACTH response between controls and experimentals as well as between males and females were significant. ACTH response to stressors was significantly blunted in both male and female experimental rats compared to their controls, but the male response was significantly lower than that of the females. These results suggest that prepubertal chronic stress may permanently alter an organism's ability to release ACTH, even when subjected to a novel and traumatic ether stress, and that males may be much more susceptible than females to prepubertal stress. Long‐term stress, therefore, if experienced during critical developmental periods such as preadolescence, can permanently damage the stress response mechanism and cause other, more serious physiological disorders.