Influence of Steroid Structure in Relation to Liver Metabolism during Endotoxin Lethality in Mice

Abstract

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-α-carbonitrile and spironolactone did not alter endotoxin lethality, liver glycogen or tryptophan pyr-rolase (TP) levels; all these materials increased liver tyrosine transaminase (TT) levels most probably due to mediation by endogeneously liberated glucocorticoid hormones. Aldosterone and deoxycorticosterone induced liver TP, TT and glycogen but did not protect against lethality. Cortisone, hydrocortisone, triamcinolone, dexamethasone and 9-α-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.

Movement-evoked hyperalgesia induced by lipopolysaccharides is not suppressed by glucocorticoids

“…While mifepristone inhibits both glucocorticoid and progesterone receptors, its protection against lethality is likely due to its ability to inhibit glucocorticoid receptors as endotoxin lethality in mice was diminished by dexamethasone but not progesterone (Lazar et al, 1977). Using this approach, which spares the adrenal but targets the action of hormones derived from the adrenal cortex, we found that mifepristone failed to influence movement-evoked hyperalgesia at a dose that enhanced the lethal effects of LPS.…”