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The metallohormone cadmium modulates AhR-associated gene expression in the small intestine of rats similar to ethinyl-estradiol.
MedLine Citation:
PMID:  23135549     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cadmium (Cd) affects the expression of estrogen receptor (ER) and aryl hydrocarbon receptor (AhR)-associated genes in rat uterus and elicits estrogen-like activity in vitro. The small intestine is highly exposed to dietary Cd which may mimic or antagonize estrogen action in this tissue. We investigated the effects of Cd and 17-alpha-ethinylestradiol (EE(2)) on AhR-associated gene expression after oral exposure of ovariectomized female Wistar rats, and metallothionein (Mt1a) expression as a typical metal-response marker. Mt1a in the small intestine was strongly induced by co-treatment with CdCl(2) at 2 mg/kg b.wt (Cd 2) and 0.1 mg/kg b.wt EE(2) than by the single compound (3-day gavage). The Cd 2-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was not antagonized by pure anti-estrogen (2.5 mg/kg b.wt ZK191703 s.c., ZK). Interestingly, the EE(2)-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was antagonized by Cd 2 in vivo and in colon cancer cell lines (HT-29 and CaCo-2, treated 5 days with Cd 1 µM and/or E(2) 0.01 µM) with low or no ER-beta expression. Dose dependency was studied after Cd exposure with drinking water (5 and 50 ppm CdCl(2) equivalent to 0.4 and 4 mg/kg b.wt; Cd 0.4, Cd 4) for 28 days and EE(2) as reference. Intestinal Mt1a expression was dose dependently induced, while AhR target genes were down-regulated by Cd 0.4 similar to EE(2) and more pronounced than by Cd 4. We propose that Cd modulates intestinal AhR-associated gene expression similar to estrogens, but (contrary to its effects in uterus) via ER-independent and/or ER-beta-mediated mechanisms. Our new data suggest interference of Cd with estrogen and AhR signaling in the small intestine.
Authors:
Felix M Kluxen; Patrick Diel; Nicola Höfer; Eugenia Becker; Gisela H Degen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Archives of toxicology     Volume:  -     ISSN:  1432-0738     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sports University Cologne, Am Sportpark Müngersdorf 6, 50933, Köln, Germany, felix.kluxen@gmail.com.
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