Endotoxin-induced inhibition of steroid binding by mouse liver cytosol

Glucocorticoids have been reported to ameliorate the lethal effects of endotoxin in a wide variety of animals, including man. Restoration of hepatic gluconeogenic enzymes and nucleotides may be involved in this effect. In this study decreased binding of 3H-dexamethasone was observed in liver cytosol preparations obtained from adrenalectomized C3HeB/FeJ mice treated with 100 micrograms of Escherichia coli 0111:B4 endotoxin (Boivin). Adrenalectomy significantly reduced th endotoxin LD50 value from 4.7 mg/kg to 2.3 micrograms/kg. The amount of labeled steroid bound by endotoxin-treated mice was 13,606 +/- 2,027 dpm/mg cytosol protein compared with 17,247 +/- 2,084 dpm/mg cytosol protein in adrenalectomized controls. Results from studies on the distribution of 14C-endotoxin suggested the inhibition of steroid binding seen in liver may be a mediated event. It is likely perturbations in steroid action at the subcellular/molecular level are involved.