Jam. Vaneekelen et al., ADRENOCORTICAL HYPORESPONSIVENESS AND GLUCOCORTICOID FEEDBACK RESISTANCE IN OLD MALE BROWN-NORWAY RATS, The journals of gerontology. Series A, Biological sciences and medical sciences, 50(2), 1995, pp. 83-89
This study was designed to examine adrenocortical function in old (30
months) and young (6 months) male Brown Norway rats. The following obs
ervations were made. First, stress induced a higher pituitary adrenoco
rticotropic hormone (ACTH) response in the aged male Brown Norway rats
than in young rats, while peak circulating corticosterone (CORT) leve
ls were not different. Moreover, this type of ''repeated'' stress invo
lving subcutaneous injection and blood sampling at various time points
by pinching the tail vein, evoked a prolonged ACTH and CORT response
in the aged animal. Second, exogenous ACTH(1-24) administered to dexam
ethasone-preheated Brown Norway rats, used as an in vivo challenge tes
t for adrenocortical function, resulted in a delayed CORT response in
the aged rats. The termination of the CORT response to ACTH, however,
was not different between young and old rats. Third, ACTH(1-24) stimul
ation of adrenocortical cells in vitro showed a tendency to a reduced
CORT output, when these cells were obtained from old animals. Fourth,
adrenalectomy (ADX) differentially affected pituitary ACTH release at
both ages. The initial post-ADX ACTH surge was more pronounced in the
aged animals. Beyond 4 days post-ADX the old Brown Norway rats did not
show the pronounced afternoon peak in circulating ACTH as was observe
d in the young animals. This study demonstrates that during the aging
process a deficiency in adrenocortical function develops in the male B
rown Norway rat. This deficiency involves a less efficient stress-indu
ced activation of adrenocortical output of CORT having enhanced pituit
ary ACTH release as one of the consequences. The deficiency of the age
d animal also involves the inability to terminate the enhanced ACTH an
d CORT response after repeated stress, probably due to an impaired cor
ticosteroid feedback.