The role of the glucocorticoid receptor (GR) in senescence was studied in r
ats of increasing age. Statistically significant changes in the number of G
Rs from rat liver were detected, whereas the affinity for the ligand triamc
inolone acetonide (TA) did not change with increasing age, and was in the r
ange of 1-2 nM. In all cases the number of receptors was lower in rats trea
ted with hormone in vivo relative to untreated animals. In addition, we hav
e found changes in GR activation, as measured by the binding to DNA cellulo
se in the mentioned age groups. Furthermore, expression of the glucocortico
id hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showe
d age-related alterations. We conclude that receptor function shows oscilla
tory changes during ageing. In addition, response to GH generally declines
towards the older age. This. specific periodicity in functional characteris
tics of the GR may reconcile conflicting results about the receptor number
and properties during the ageing process, and marks particular age at which
individual organism shows the highest or the lowest sensitivity to the act
ions of GH. (C) 1999 Elsevier Science Inc. All rights reserved.