Delayed luteolysis after intra-uterine infusions of nordihydroguaiaretic acid in the ewe

Intrauterine administration of nordihydroguaiaretic acid (5 mg, bid. NDGA), an inhibitor of the enzyme 5-lipoxygenase, on days 10–14 of the oestrous cycle, maintained luteal function and delayed oestrus in the ewe. The duration (mean±SD) of the oestrous cycle in the treatment group (n=4) was 24±1 days, which was significantly (P<0.001) longer than that of 16±1 days in vehicle-treated controls (n=4); plasma progesterone concentrations were also significantly (P<0.01) higher in the treatment group. On days 13 and 14 of the cycle (oestrus=Day 0) in the control group large pulses of 13,14-dihydro-15-keto prostaglandin F2α (PGFM) were evident, with mean (±SD) maximum concentrations of 232.5±66 and 415±309 pg ml−1, respectively. In the treatment group, however, concentrations of PGFM were below detection level (<50 pg ml−1). Similarly, in the control group, oxytocin release was highly pulsatile, with mean (±SD) peak concentrations of 21.8±5 and 18.5±6 pg ml−1 on days 13 and 14, respectively; these were significantly (P<0.01) higher than values of 7.6±3 and 6.1±3 pg ml−1 in NDGA-treated ewes, where pulses were of relatively low amplitude. These results suggest that 5-lipoxygenase products of arachidonic acid metabolism may be involved in the positive feedback mechanism between luteal oxytocin and uterine PGF2α during luteolysis in the ewe.