Non-estrogenic metabolites of diethylstilbestrol produced by prostaglandin synthase mediated metabolism.
Incubation of trans-diethylstilbestrol (E-DES) with prostaglandin synthase (PGS) in vitro leads to the formation of the metabolites cis, cis-dienestrol (Z,Z-DIES) and cis-diethylstilbestrol (Z-DES) which have considerably decreased estrogenic activity compared to their parent compound. Incubations of (14C)-E-DES with PGS in the presence of arachidonic acid (AA) predominantly catalyze formation of the oxidative metabolite Z,Z-DIES, accompanied by the formation of protein bound radioactivity. Inhibition of peroxidative metabolism through addition of indomethacin or absence of AA favors isomerization of E-DES to Z-DES without concomitant formation of protein bound radioactivity. Isomerization is inhibited by phenidone (1-phenyl-3-pyrazolidone). Since PGS activity is present in uterine tissue, these pathways may play a role in the metabolism of DES in its target tissue.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D004028:Dienestrol / Q000378:metabolism; D004054:Diethylstilbestrol / Q000378:metabolism*; D007536:Isomerism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012756:Sheep
D001095:Arachidonic Acids; D011720:Pyrazoles; D016718:Arachidonic Acid; D004054:Diethylstilbestrol; D011451:Prostaglandin-Endoperoxide Synthases; C015429:phenidone; D004028:Dienestrol