Influence of steroid structure in relation to liver metabolism during endotoxin lethality in mice.
The influence of a number of steroid molecules on hepatic metabolism was determined in relationship to their ability to alter endotoxin lethality in intact mice. Progesterone, testosterone, estradiol, pregnenolone-16-alpha-carbonitrile and spironolactone did not alter endotoxin lethality, liver glycogen or tryptophan pyrrolase (TP) levels; all these materials increased liver tyrosine transaminase (TT) levels most probably due to mediation by endogenously liberated glucocorticoid hormones. Aldosterone and deoxycorticosterone induced liver TP, TT and glycogen but did not protect against lethality. Cortisone, hydrocortisone, triamcinolone, dexamethasone and 9-alpha-fluorohydrocortisone protected against lethality, increased liver glycogen and TT, but only triamcinolone induced liver TP. Collectively, there was no clear relationship between the protective effect and the increase or decrease of a given liver process. These further emphasize the need to reconsider molecular mechanisms of endotoxic reactions.
D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008901:Mineralocorticoids / Q000494:pharmacology; D012486:Salmonella typhimurium; D013256:Steroids / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000378:metabolism
D001427:Bacterial Toxins; D004731:Endotoxins; D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D008112:Liver Glycogen; D008901:Mineralocorticoids; D013256:Steroids; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase