Mercury inhibits rat liver and kidney glucocorticoid receptor hormone binding activity.
The present study was focused on the influence of mercury on the rat liver and kidney glucocorticoid receptor (GR) binding properties. The time-course and dose-dependence of mercury effects, as well as possible involvement of thiol groups were examined after in vivo and in vitro administration of the metal in the form of HgCl2. Mercury led to reduction of the liver and kidney GR hormone binding capacity. In both examined tissues maximal reduction was noticed 4 h after administration of the metal at 2 and 3 mg Hg/kg bw, but the effect was more prominent in kidney as compared to liver. On the other hand, binding affinity in the two tissues was similar. The complete reversal of mercury effects on GR binding capacity by 10 mmol/L DTT was achieved in liver and partially in kidney. The reversal by DTT suggested that mercury caused the decrease of GR binding activity by interacting with thiol groups. The difference in the response of the two tissues reflected the fact that kidney contained a higher mercury concentration and a lower thiol content in comparison to liver. The implicated thiols probably belong to GR, since when applied in vitro at 0 degrees C, mercury produced reduction of the receptor binding activity similar to that observed in vivo. GR protein level examined by quantitative Western blot was either unchanged, when determined by polyclonal antibody, or reduced, when determined by BuGR2 antibody, suggesting that Hg might affect BuGR epitope availability.
Brkljacić
J
J
Department of Biochemistry, Institute for Biological Research, Belgrade, Serbia and Montenegro.
Vojnović Milutinović
D
D
Dundjerski
J
J
Matić
G
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008628:Mercury / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000378:metabolism; D014316:Tritium
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D013438:Sulfhydryl Compounds; D014316:Tritium; D014222:Triamcinolone Acetonide; D008628:Mercury