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Characterization of 3-Methylcholanthrene Effects on the Rat Glucocorticoid Receptor in Vivo

Laboratory of Experimental Oncology, Nestlé Research Centre, NESTEC Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland

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 [B_max = 209 ± 3 (SE) fmol/mg of protein] compared to the vehicle-treated controls (B_max = 277 ± 13 fmol/mg) but had no significant influence on the affinity of the GRc (K_d = 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 B_max and K_d values compared to the vehicle treated controls (P < 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.

¹ To whom requests for reprints should be addressed, at Nestlé Research Centre, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland.

Received 1/18/89. Revised 3/27/89. Accepted 4/ 4/89.