EFFECT OF ESTRADIOL ON ENDOTOXIN-INDUCED CHANGES IN STEROID-HORMONE LEVELS AND LETHALITY IN MALE-RATS

We examined the effect of exogenous estradiol on the changes in serum steroid hormone levels induced by a nonlethal dose of Escherichia coil endotoxin in male rats and the deaths due to nonlethal and lethal dos es of endotoxin. Injection of estradiol 5 min before a nonlethal dose of endotoxin changed the serum sex steroid hormone response of male ra ts to endotoxin. The serum estrogen concentrations of estradiol + endo toxin-treated rats decreased by 50% (P < 0.001), while those of the en dotoxin-treated rats increased (2- to 5-fold). The serum androgen conc entrations of estradiol + endotoxin-treated rats did not change signif icantly, while those of endotoxin-treated rats dropped to 30-40%, P < 0.001. Exogenous estradiol also appeared to influence the percentage o f endotoxin-induced deaths in a dose-dependent manner. It reduced the number of deaths induced by nonlethal (2 mg/kg) dose of endotoxin but increased the number of deaths induced by a highly lethal dose (8 mg/k g). These results, together with the known relationships between estro gen and the immune response, suggest that estrogens affect the course of septic shock in a complex fashion and may have either protective or deleterious effect. (c) 1995 Wiley-Liss, Inc.