Antifertility effect of azastene mediated by prostaglandin

Azastene, a synthetic steroid of the androstano (2,3-d) isoxazole family, has been shown to terminate pregnancy in the rat and in the primate. Its antifertility effect in the rat is associated with a decrease of progesterone and an increase in prostaglandin F (PGF). Its mechanism of action has been explained by the ability of azastene to inhibit 3β-hydroxysteroid dehydrogenase, thereby critically decreasing progesterone production. However, azastene-induced PGF release could be directly responsible for the decreased progesterone production and hence for its antifertility effect. To test this hypothesis PGF release associated witch azastene administration was blocked by indomethacin. In indomethacin-treated rats, azastene administered at day 10 of pregnancy failed to decrease uterine blood progesterone [100.6±11 (mean±SE) ng/ml (N=10) for azastene-indomethacin–treated rats versus 30.6±4.4 (mean±SE) ng/ml (N=10) for azastene alone; p