General effect of endotoxin on glucocorticoid receptors in mammalian tissues.
Considering the ubiquitous nature of glucocorticoid actions and the fact that endotoxin inhibits glucocorticoid action in the liver, we proposed to examine whether endotoxin affected extrahepatic actions of glucocorticoids. Fasted C57BL/6J mice were injected intraperitoneally with endotoxin (LD50) at 0800 and were killed 6 h later. Control mice were injected with an equal volume of saline. 3H-dexamethasone binding, measured by a new cytosol exchange assay utilizing molybdate plus dithiothreitol, in liver, kidney, skeletal muscle, spleen, lung, and heart tissue was significantly lower in treated than in control mice. The equilibrium dissociation constants were not significantly different, but the number of available binding sites in each tissue was reduced by endotoxin treatment. Phosphoenolpyruvate carboxykinase activity was significantly reduced in liver but not in kidney. Endotoxin treatment lowered glycogen content in liver but not in skeletal muscle. The reduction observed in the "a" form of liver glycogen synthase due to endotoxin was not seen in skeletal muscle glycogen synthase "a." These data support the proposal that endotoxin or a mediator of its action inhibits systemic glucocorticoid action. The results also emphasize the central role of the liver in the metabolic disturbances of the endotoxin-treated mouse.
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D000818:Animals; D001665:Binding Sites; D003907:Dexamethasone; D004731:Endotoxins / Q000494:pharmacology*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D012486:Salmonella typhimurium; D012772:Shock, Septic / Q000378:metabolism*; D014316:Tritium
D004731:Endotoxins; D005938:Glucocorticoids; D008112:Liver Glycogen; D011965:Receptors, Glucocorticoid; D014316:Tritium; D003907:Dexamethasone; D006003:Glycogen; D006006:Glycogen Synthase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)