Diminished diurnal secretion of adrenocorticotropin (ACTH), but not corticosterone, in old male rats: possible relation to increased adrenal sensitivity to ACTH in vivo.

Abstract

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.