Document Detail


The fate of diethylstilbestrol in the pregnant mouse.
MedLine Citation:
PMID:  819646     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H C Shah; J A McLachlan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  197     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1976 Jun 
Date Detail:
Created Date:  1976-09-01     Completed Date:  1976-09-01     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  687-96     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Proteins / metabolism
Diethylstilbestrol / analysis,  metabolism*,  urine
Feces / analysis
Female
Fetus / metabolism
Glucuronosyltransferase / metabolism
Kinetics
Liver / metabolism
Maternal-Fetal Exchange
Mice
Pregnancy*
Protein Binding
Chemical
Reg. No./Substance:
0/Blood Proteins; 56-53-1/Diethylstilbestrol; EC 2.4.1.17/Glucuronosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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