ABSTRACT
The effects of cadmium (Cd) administration to intact rats on hepatic glucocorticoid receptor (GR) steroid binding capacity and DNA-binding ability were examined and correlated with the influence of the metal on rat liver tyrosine aminotransferase (TAT) activity and its induction by dexamethasone. It was found that 24 h after i.p. administration of Cd doses ranging from 0.5 to 4 mg/kg, the GR steroid- and DNA-binding activities were significantly reduced in a dose-dependent manner. The same doses of Cd also affected the basal and dexamethasone-induced level of TAT activity, as well as the concentration of metallothionein in rat liver. The decrease in TAT activity and in its induction by dexamethasone observed in response to low Cd doses was proportional to the alterations of the GR functional properties. Higher doses of Cd, which were more effective in reducing both the GR binding of the hormone and to DNA, however, stimulated TAT activity and potentiated dexamethasone induction of the enzyme. The results led to the conclusion that Cd may alter physiological response of rat liver cells to glucocorticoids interfering with the GR-dependent transcriptional regulation of the TAT gene.
Subject(s)
Cadmium/toxicity , Dexamethasone/pharmacology , Liver/drug effects , Liver/enzymology , Tyrosine Transaminase/biosynthesis , Animals , Enzyme Induction/drug effects , Male , Rats , Rats, Wistar , Receptors, Glucocorticoid/drug effects , Tyrosine Transaminase/antagonists & inhibitorsABSTRACT
A mild whole body hyperthermic stress causes a rapid and reversible reduction of rat liver glucocorticoid receptor (GR) binding capacity and affects the stability of the GR-DNA complexes formed after thermal transformation of the receptor. These changes appear to be physiologically relevant, since they are accompanied by a decrease in dexamethasone induction of hepatic tyrosine aminotransferase (TAT). In spite of the decreased rate of the GR degradation in liver cytosol of hyperthermic as compared to control rats, the total amount of the GR and its proteolytic products recognized by BuGR2 monoclonal antibody was found to be lower in the former cytosol, but higher in the respective nuclei.
