A ROLE FOR LIPOXYGENASE METABOLITES OF ARACHIDONIC-ACID IN PORCINE OVULATION

Prostaglandins, products of arachidonic acid via,he cyclooxygenase pat hway, are essential to the porcine ovulatory process in that inhibitio n of their synthesis results in ovulation failure. Studies in the rat have shown that ovulation is also preceded by a rise in three ovarian hydroxyeicosatetraenoic acids, products of the lipoxygenase pathway, a nd inhibition of this pathway also inhibits ovulation. Experiments wer e designed, using a pregnant mare serum gonadotropin/human chorionic g onadotropin (hCG)-treated prepuberal gift model, to measure pre-ovulat ory changes in follicular fluid concentrations of 15-hydroxyeicosatetr aenoic acid (15-HETE), and to compare the effects of indomethacin and nordihydroguaiaretic acid (NDGA) on ovulation in the pig and on 15-HET E and prostaglandin F-2 alpha synthesis both in vivo and in vitro. Fol licular fluid concentrations of 15-HETE were elevated significantly ju st prior to the expected time of ovulation (40 h after hCG). When indo methacin (10 mg) was injected into the ovarian stalk at 24 h after hCG , follicular fluid concentrations of both 15-HETE and prostaglandin F- 2 alpha were lower (P < 0.01) than controls at 40 h and ovulation rate was suppressed (P < 0.01). When NDGA (5 mg) was administered in the s ame manner, ovulation rate was suppressed (P < 0.01), but the levels o f 15-HETE and prostaglandin F-2 alpha were not altered. Synthesis of 1 5-HETE by cultured granulosa and theca interna cells was reduced by th e presence of NDGA (1 mg/ml), whereas indomethacin (100 ng/ml) lowered 15-HETE production in theca interna cells only. These results clearly demonstrate that indomethacin can block the lipoxygenase as well as t he cyclooxygenase pathways, depending on the dose used, and suggest th at lipoxygenase metabolites of arachidonic acid are involved in the ov ulatory process in the pig. (C) 1998 Elsevier Science B.V.