Sex steroid hormones modulate the activation of murine peritoneal macrophages: Receptor mediated modulation

The comparative dose and time-dependent effects of male and female sex steroid hormones on nitrite release by murine peritoneal macrophages (M phi) stimulated by LPS were studied. M phi from gonadectomized mice released larger amounts of nitrite on LPS stimulation than controls; although nitrite release was significantly greater in castrated males than in ovariectomized females, suggesting that sex hormone deprivation results in an increase in nitrite release. This was further confirmed by in vitro treatment of M phi with estradiol (E-2), testosterone (T) and progesterone (P) at different doses and duration prior to, and during, stimulation of nitrite production by LPS. E-2 (except at 10(-2) ng/ml), T and P significantly (P < 0.05) suppressed the nitrite release in a dose-dependent manner. Nitrite release from M phi increased with decreasing exposure time to E-2, T and P. Preincubation of M phi with sex hormones prior to LPS treatment also reduced nitrite production. Sex steroid receptor antagonists tamoxifen citrate, cyproterone acetate/flutamide and RU486 markedly reduced the inhibitory effect of E-2, T and P, respectively, suggesting that sex hormones modulate M phi nitrite release via a receptor-mediated system. (C) 1998 Elsevier Science Inc.