Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 50, Issue 2 B83-B89, Copyright © 1995 by The Gerontological Society of America
Adrenocortical hyporesponsiveness and glucocorticoid feedback resistance in old male brown Norway rats
JA Van Eekelen, MS Oitzl and ER De Kloet
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
This study was designed to examine adrenocortical function in old (30
months) and young (6 months) male Brown Norway rats. The following
observations were made. First, stress induced a higher pituitary
adrenocorticotropic hormone (ACTH) response in the aged male Brown Norway
rats than in young rats, while peak circulating corticosterone (CORT)
levels were not different. Moreover, this type of "repeated" stress
involving 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 ACTH1-24 administered to
dexamethasone-pretreated Brown Norway rats, used as an in vivo challenge
test 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, ACTH1-24 stimulation 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 observed in the young animals.
This study demonstrates that during the aging process a deficiency in
adrenocortical function develops in the male Brown Norway rat. This
deficiency involves a less efficient stress-induced activation of
adrenocortical output of CORT having enhanced pituitary ACTH release as one
of the consequences.(ABSTRACT TRUNCATED AT 250 WORDS)
