CADMIUM AFFECTS THE ACTIVITY OF RAT-LIVER TYROSINE AMINOTRANSFERASE AND ITS INDUCTION BY DEXAMETHASONE

The effects of cadmium (Cd) administration to intact rats on hepatic g lucocorticoid receptor (GR) steroid binding capacity and DNA-binding a bility 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 lev el of TAT activity, as well as the concentration of metallothionein in rat liver. The decrease in TAT activity and in its induction by dexam ethasone 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 an d to DNA, however, stimulated TAT activity and potentiated dexamethaso ne 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 T AT gene.