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.
Sunahara
G I
GI
Laboratory of Experimental Oncology, Nestlé Research Centre, NESTEC Ltd., Lausanne, Switzerland.
Guenat
C
C
Grieu
F
F
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D002273:Carcinogens; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D008748:Methylcholanthrene; D003907:Dexamethasone; D010634:Phenobarbital