Basal and glucocorticoid induced changes of hepatic glucocorticoid receptor during aging: relation to activities of tyrosine aminotransferase and tryptophan oxygenase.
The characteristics of glucocorticoid receptors, their sensitivity to glucocorticoid as well as the basal and glucocorticoid induced thyrosine aminotranferase (TAT) and tryptophan oxygenase (TO) activities were studied in rat liver during aging. The concentration (N) and dissociation constant (K(d)) of glucocorticoid receptor (GR) significantly change during the aging both in untreated and dexamethasone treated animals. The level of receptors was lower in dexamethasone treated rats of all analyzed aged groups compared to untreated animals. In comparison to untreated groups, there was no correlation between the changes of N and K(d) during the lifespan. According to immunochemical analysis, the decline of receptor protein content occurs during lifespan. Dexamethasone treatment reduced the level of receptor protein compare to respective age group of untreated rats. The glucocorticoid-receptor (G-R) complexes from both untreated and treated animals underwent thermal activation, although the extent of activation was more pronounced in the case of untreated groups compared to treated animals. The magnitude of heat activation of receptor complexes was more pronounced in the liver of the youngest untreated rats compared to elderly ones, while the receptor activation between treated groups of studied ages has shown less significant differences. Besides, basal as well as induced TAT and TO activities after dexamethasone injection also showed age-related alterations. The observed alterations in GR might play a role in the changes of the cell responses to glucocorticoid during the age. This presumption is supported by detected changes in basal and dexamethasone induced TAT and TO activities during aging.
Ribarac-Stepić
Nevena
N
Department for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Serbia and Montenegro. nrs@rt270.vin.bg.ac.yu
Vulović
Mojca
M
Korićanac
Goran
G
Isenović
Esma
E
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage*; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014018:Tissue Distribution; D014366:Tryptophan Oxygenase / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000378:metabolism*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase