The fate of diethylstilbestrol in the pregnant mouse.
There is much current interest in the effect of diethylstilbestrol (DES) on the mammalian fetus; however, little is known concerning the physiologic disposition of DES during pregnancy. Radiolabeled (14C or 3H) DES (30 mug/kg) was given to 16-day pregnant mice and its metabolism, distribution and excretion were studied. After i.v. administration, DES was rapidly cleared from the plasma. The plasma decay rates could be described by the sum of four exponentials having T 1/2 values of 4 seconds, 1.1 minutes, 14 minutes and 13 hours. Moreover, conjugated products of DES accounted for more than one-half of the plasma radioactivity by 5 minutes after dosing. The parent compound was rapidly distributed to blood cells, but the liver was the major site of accumulation of DES and its metabolites. In fact, the total radioactivity in this organ accounted for 50% of the injected dose within 2.5 minutes after treatment. Significant concentrations of radioactivity persisted in liver throughout the 16-hour experiment, with DES conjugates accounting for 80% of the hepatic 14C activity at all time points examined. Approximately 56% of the dose was excreted in the feces within 24 hours, primarily as the parent compound. With DES as substrate, significant levels of UDP-glucuronyltransferase were determined in maternal and fetal liver but not in maternal uterus, placenta of fetal gut. Although the mouse placenta appeared to retard the passage of DES into the fetal compartment, a 3-fold accumulation (relative to fetal plasma) of the compound was found in the fetal reproductive tract.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004054:Diethylstilbestrol / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D005243:Feces / Q000032:analysis; D005260:Female; D005333:Fetus / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011485:Protein Binding
D001798:Blood Proteins; D004054:Diethylstilbestrol; D014453:Glucuronosyltransferase