Document Detail


Estrogenic activity of zearalenone and zearalanol in the neonatal rat uterus.
MedLine Citation:
PMID:  6235618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fusarium sp. contaminated feedstuffs elicit adverse estrogenic effects in several commercially important animal species via the mycotoxin zearalenone. An estrogenically active synthetic derivative, zearalanol, is used as an anabolic agent in cattle. Since estrogens can irreversibly alter target tissue development, we investigated the estrogenic activity of these compounds in the neonatal rat uterus. Both induced dose-dependent premature uterine growth when injected daily on postnatal days 1-5 (ED50 = 1.3 mg/kg BW). Nuclear estrogen receptor levels dramatically increased 1 hour after either a single injection on day 5 or after five daily injections. In 5-day-old animals, the translocated nuclear receptor was characterized as a single class of binding sites with a dissociation constant (KD) for estradiol (E2) of 1 nM. At 15 days, zearalanol-treated animals showed greater uterine nuclear receptor retention than zearalenone-treated animals. In 5-day-old animals, single mycotoxin doses induced five fold elevations of ornithine decarboxylase (ODC) at 6 hours. Unlike the growth response, ODC dose-response studies showed zearalanol to be about 20-fold more effective than zearalenone. Time course studies revealed that a low dose of zearalenone, but not of zearalanol, resulted in a shift in peak activity from 6 to 8 hours. These data suggest that metabolism of zearalenone may be important in short-term pharmacodynamics. In a competitive binding assay, neither compound competed [3H]E2 from the E2 binding site on alpha-fetoprotein. We conclude that the uterine growth response and ODC induction demonstrate the neonatal estrogenic action of these mycotoxins, apparently mediated via the estrogen receptor. The greater effectiveness of zearalanol in inducing ODC may be related to nuclear retention and/or zearalenone metabolism.
Authors:
D M Sheehan; W S Branham; K L Medlock; E R Shanmugasundaram
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Teratology     Volume:  29     ISSN:  0040-3709     ISO Abbreviation:  Teratology     Publication Date:  1984 Jun 
Date Detail:
Created Date:  1984-09-05     Completed Date:  1984-09-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0153257     Medline TA:  Teratology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  383-92     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn*
Enzyme Induction / drug effects
Female
Organ Size / drug effects
Ornithine Decarboxylase / biosynthesis,  metabolism
Rats
Receptors, Estrogen / drug effects,  metabolism
Resorcinols / pharmacology*
Uterus / drug effects*,  enzymology,  growth & development,  metabolism
Zearalenone / metabolism,  pharmacology*
Zeranol / metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Receptors, Estrogen; 0/Resorcinols; 17924-92-4/Zearalenone; 26538-44-3/Zeranol; EC 4.1.1.17/Ornithine Decarboxylase

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


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