The adrenocortical axis in the aged rat: impaired sensitivity to both fast and delayed feedback inhibition

Abstract

Aged rats secrete excessive amounts of the species-typical glucocorticoid, corticosterone, under basal conditions, following the end of stress and during habituation to mild stressors. Furthermore, the aged rat is resistant to the inhibitory effects of the synthetic glucocorticoid dexamethasone upon subsequent corticosterone secretion. These observations have led to the hypothesis that the aged adrenocortical axis is desensitized to the inhibitory effects of glucocorticoids. In the present study, we have defined this negative-feedback deficit more precisely. The aged adrenocortical axis is subject to both rate-sensitive fast feedback regulation by corticosterone and to level-sensitive delayed feedback. Moreover, there is no age difference in the maximal extent of feedback inhibition which can be attained. However, the sensitivity to both forms of feedback regulation is diminished in aged rats, in that the aged adrenocortical axes are responsive under feedback conditions which completely inhibit corticosterone secretion in young animals. Such insensitivity is likely to underlie the incidences of hyperadrenocorticism apparent in the aged rat; we speculate that progressive degeneration in the aged hippocampus might be the cause of this dampened sensitivity to feedback inhibition.