Further evidence for role of leukotrienes as mediators of decidualization in the rat

Abstract

Inhibitors of leukotrieens were utilized to investigate the role of leukoteines (LTs) in the induction of decidualization in the rat. Alzet osmotic minipumps, filled with either FPL 55712 (FPL, a specific antagonist of peptidoleukotrienes), nordihydroguaiaretic acid (NDGA, an inhibitor of LT synthesis) or in combination with leukotriene C 4 (LTC 4) and/or prostaglandin E2 (PGE 2), were instilled at the ovarian end of uterine horns of day 5 pseudopregnant rats. Intraluminal infusion of FPL or DNGA, for 4 days, induced a dose dependent decrease in the uterine wet weights when compared to that induced by the infusion of their corresponding vehicles (1 μl/h). Furthermore, simultaneous infusion of LTC 4 (10 ng/h) with different doses of FPL (1, 0.5, or 0.25 μg/h) produced an increase in uterine weights as compared to that produced by FPL alone. Maximum response, however, was noted when LTC 4 (n0 ng/h) was infused with FPL at a rate of 0.5 μg/h. The infusion of LTC 4 (10 ng/h) or PGE 2 (1 μg/h) with NDGA, at 1 and 5 μg/h, could not overcome its inhibitory effect on decidualization. On the contrary, a combination of LTC 4 (10 ng/h) and PGE 2 (1 μg/h) was comparable to that induced by the infusion of the vehicle. To determine if the synthesis of PGs and LTs was inhibited by NDGA, one uterine horn was infused with NDGA (5 μg/h) and the other horn with the vehicle. The intrauterine infusion of NDGA for 24 h inhibited the release of PGE 2, PGF 2α, LTC 4 and LTB 4 as compared to those released by the vehicle-infused horns. These data suggest that both PGs and LTs are required for the induction and progression of decidualization.