Document Detail


The metabolism of 2- and 4-fluoro-17 beta-oestradiol in the rat and its implications for oestrogen carcinogenesis.
MedLine Citation:
PMID:  1554397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2-Fluoro-[6,7-3H]17 beta-oestradiol([3H]2-FE2) and 4-fluoro-[6,7-3H]17 beta-oestradiol([3H]4-FE2) were synthesized by the fluorination and reduction of [3H]oestrone and purified by HPLC. [3H]2-FE2 and [3H]4-FE2 (72.5 micrograms/kg; 0.25 mumol/kg) were administered i.v. to anaesthetized female and male Wistar rats (N = 4) with biliary cannulae. Bile was collected for 6 hr. Female rats administered [3H]2-FE2 excreted 85% of the dose into bile over 6 hr whilst male rats excreted 77%. After the administration of [3H]4-FE2, female and male rats excreted 72 and 83% of dose into bile over 6 hr, respectively. The biliary metabolites were glucuronides in all cases. The principal metabolite of [3H]2-FE2 liberated from biliary conjugates by beta-glucuronidase was 2-fluoroestrone in both female rats (64% of dose) and male rats (57%). No 2-hydroxylated, i.e. oxidatively defluorinated, metabolites were detected in either sex. In contrast, 2-hydroxylation of [3H]4-FE2 did occur, but only in female rats: 2-hydroxy-4-fluoro-oestrone (22%) and 2-methoxy-4-fluoroestrone (17%) were identified as biliary aglycones. However, the major metabolite was 4-fluoroestrone (4FE1; 38%). In male rats, 4-FE1 and 4-fluoro D-ring-oxygenated products were the principal biliary aglycones. The differences in metabolism between the two fluoro analogues and oestradiol are discussed with particular reference to the possible involvement of 2- and 4-hydroxy (catechol) oestrogens in oestrogen toxicity.
Authors:
P Morgan; J L Maggs; P C Bulman-Page; F Hussain; B K Park
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  43     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1992 Mar 
Date Detail:
Created Date:  1992-04-28     Completed Date:  1992-04-28     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  985-93     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile / metabolism
Biotransformation
Chromatography, High Pressure Liquid
Estradiol / analogs & derivatives*,  chemical synthesis,  metabolism
Female
Glucuronates / metabolism
Male
Mass Spectrometry
Metabolic Detoxication, Drug
Rats
Rats, Inbred Strains
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Glucuronates; 16205-32-6/2-fluoroestradiol; 1881-37-4/4-fluoroestradiol; 50-28-2/Estradiol

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