Characterization of 3-methylcholanthrene effects on the rat glucocorticoid receptor in vivo

The effects of 3-methylcholanthrene and phenobarbital treatment on the adult rat hepatic cytosolic glucocorticoid (GRc) receptor were investigated. Analyses of sucrose gradient profiles and equilibrium binding data of [3H]dexamethasone bound to the GRc revealed that administration of 3-methylcholanthrene (20-40 mg/kg daily i.p. for 2 days) to adult female Fischer F344 rats led to a significant decrease in the maximal binding capacity of the 5-7S GRc [Bmax = 209 +/- 3 (SE) fmol/mg of protein] compared to the vehicle-treated controls (Bmax = 277 +/- 13 fmol/mg) but had no significant influence on the affinity of the GRc (Kd = 0.9 +/- 0.1 nM). This response was not dependent upon the sex or rat strain (female F344 versus Sprague-Dawley). Phenobarbital treatment (80 mg/kg daily i.p. for 4 days) decreased Bmax and Kd values compared to the vehicle treated controls (P less than 0.05). 3-Methylcholanthrene treatment did not significantly alter the equilibrium parameters of [3H]methyltrienolone bound to the hepatic androgen receptor indicating that the effect was specific to the hepatic GRc. Our data suggest that carcinogens and tumor promoters cause a functional decrease of the cytosolic glucocorticoid receptor in vivo.