Lipoxygenase activity in human uterine and intrauterine tissues: new prospects for control of prostacyclin production in pre-eclampsia.
The formation of lipoxygenase metabolites by human uterine and intrauterine tissues was evaluated using [1-14C]arachidonic acid (AA) as substrate. The major lipoxygenase product synthesized by human amnion, decidua vera and placenta was identified as 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE); smaller amounts of 5-HETE and 5-HETE (lactone form) were also formed. In chorion laeve only a trace amount of 12-HETE was detected. Human myometrium and cervical tissue converted [1-14C]AA to 5-HETE and 12-HETE in almost equal amounts. The formation of lipoxygenase products in all tissues was markedly inhibited by nordihydroguaiaretic acid (NDGA) an inhibitor of lipoxygenase activity and slightly stimulated or inhibited by indomethacin, an inhibitor of cyclooxygenase activity. These results are indicative that uterine and intrauterine tissues are probably potential sources of lipoxygenase products during pregnancy and parturition. Since 12-hydroperoxy-eicosatetraenoic acid (12-HPETE), the labile precursor of 12-HETE potently inhibits prostacyclin biosynthesis, our findings are suggestive of the possibility that aberrant lipoxygenase activities may contribute to the complications of pre-eclampsia.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D002584:Cervix Uteri / Q000201:enzymology; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D009637:Masoprocol; D009215:Myometrium / Q000201:enzymology; D011225:Pre-Eclampsia / Q000201:enzymology / Q000209:etiology*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D014599:Uterus / Q000201:enzymology*
D001095:Arachidonic Acids; D002396:Catechols; D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D009637:Masoprocol; D011464:Epoprostenol; D008084:Lipoxygenase; D007213:Indomethacin