NON-ESTROGENIC METABOLITES OF DIETHYLSTILBESTROL PRODUCED BY PROSTAGLANDIN SYNTHASE MEDIATED METABOLISM

Article abstract of DOI:10.1016/0039-128X(83)90038-7

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.