Basal and glucocorticoid induced changes of hepatic glucocorticoid receptor during aging: relation to activities of tyrosine aminotransferase and tryptophan oxygenase

Abstract

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.

Effects of Illicit Dexamethasone upon Hepatic Drug Metabolizing Enzymes and Related Transcription Factors mRNAs and Their Potential Use As Biomarkers in Cattle

“…In cattle hepatocytes, DEX did not induce CYP3A in a dose-dependent way (10); moreover, it has been recently hypothesized that neither therapeutic nor growth-promoting schedules upregulate target bovine DMEs (3). Usually, CYP3A upregulation follows DEX binding with GR or PXR (16), and TAT typically reflects changes in GR gene expression (16,21,23,24). In the present study, DEX did not affect CYP3A28 and TAT mRNA, similar to veal calves to whom similar amounts of the corticosteroid (about 10 times lower than therapeutic ones) were administered with a milk replacer (17,18).…”

Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

“…Importantly, glucocorticoid sensitivity is reduced during aging as well as in COPD patients. For example, changes in cellular responses to glucocorticoid [ 46 ] and decline in the expression of glucocorticoid receptors [ 47 ] were reported in both elderly and COPD patients.…”

Effect of acute adrenalectomy on rat liver glucocorticoid receptor

“…Binding parameters such as the number of binding sites (N) and the appropriate equilibrium dissociation constant (Kd) were obtained as previously described (Ribarac-Stepić et al, 2005;I s e n o v i ć et al, 2006) and expressed as fmol/mg of protein and nmol/l, respectively, according to Scatchard analysis (Scatchard, 1949). The binding parameters were calculated using regression analysis of Scatchard plots by computer program (L e a k e and H a b i b, 1987).…”

“…Complexes formed during incubation of the cytosolic fraction with 20 nmol/l of [ 3 H] TA at 4 o C for 18 h were activated by exposure to 25 o C for 30 min as we described previously (R i b a r a c -S t e p i ć et al., 2005;Isenović et al, 2006). The extracted radioactivity was measured and expressed as decays per minute per milligram of protein.…”