Estrogen-Like Effects of Cadmium in Vivo Do Not Appear to be Mediated via the Classical Estrogen Receptor Transcriptional Pathway.

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Title: Estrogen-Like Effects of Cadmium in Vivo Do Not Appear to be Mediated via the Classical Estrogen Receptor Transcriptional Pathway.
Authors: Ali, Imran1 (AUTHOR), Penttinen-Damdimopoulou, Pauliina E.2 (AUTHOR), Mäkelä, Sari I.2 (AUTHOR), Berglund, Marika1 (AUTHOR), Stenius, Ulla1 (AUTHOR), Åkesson, Agneta1 (AUTHOR), Håkansson, Helen1 (AUTHOR), Halldin, Krister1 (AUTHOR) Krister.Halldin@ki.se
Source: Environmental Health Perspectives. Oct2010, Vol. 118 Issue 10, p1389-1394. 6p. 1 Chart, 5 Graphs.
Subject Terms: *Cadmium, *Food contamination, *Chemical reactions, Estrogen receptors, Anthropometry
Abstract: BACKGROUND: Cadmium (Cd), a ubiquitous food contaminant, has been proposed to be an endocrine disruptor by inducing estrogenic responses in vivo. Several in vitro studies suggested that these effects are mediated via estrogen receptors (ERs). OBJECTIVE: We performed this study to clarify whether Cd-induced effects in vivo are mediated via classical ER signaling through estrogen responsive element (ERE)-regulated genes or if other signaling pathways are involved. METHODS: We investigated the estrogenic effects of cadmium chloride (CdCl2) exposure in vivo by applying the Organisation for Economic Co-operation and Development (OECD) rodent uterotrophic bioassay to transgenic ERE-luciferase reporter mice. Immature female mice were injected subcutaneously with CdCl2 (5, 50, or 500 µg/kg body weight) or with 17α-ethinylestradiol (EE2) on 3 consecutive days. We examined uterine weight and histology, vaginal opening, body and organ weights, Cd tissue retention, activation of mitogen-activated protein kinase (MAPK) pathways, and ERE-dependent luciferase expression. RESULTS: CdCl2 increased the height of the uterine luminal epithelium in a dose-dependent manner without increasing the uterine wet weight, altering the timing of vaginal opening, or affecting the luciferase activity in reproductive or nonreproductive organs. However, we observed changes in the phosphorylation of mouse double minute 2 oncoprotein (Mdm2) and extracellular signal-regulated kinase (Erk1/2) in the liver after CdCl2 exposure. As we expected, EE2 advanced vaginal opening and increased uterine epithelial height, uterine wet weight, and luciferase activity in various tissues. CONCLUSION: Our data suggest that Cd exposure induces a limited spectrum of estrogenic responses in vivo and that, in certain targets, effects of Cd might not be mediated via classical ER signaling through ERE-regulated genes. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Estrogen-Like Effects of Cadmium in Vivo Do Not Appear to be Mediated via the Classical Estrogen Receptor Transcriptional Pathway.
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  Data: <searchLink fieldCode="AR" term="%22Ali%2C+Imran%22">Ali, Imran</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Penttinen-Damdimopoulou%2C+Pauliina+E%2E%22">Penttinen-Damdimopoulou, Pauliina E.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mäkelä%2C+Sari+I%2E%22">Mäkelä, Sari I.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Berglund%2C+Marika%22">Berglund, Marika</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stenius%2C+Ulla%22">Stenius, Ulla</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Åkesson%2C+Agneta%22">Åkesson, Agneta</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Håkansson%2C+Helen%22">Håkansson, Helen</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Halldin%2C+Krister%22">Halldin, Krister</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> Krister.Halldin@ki.se</i>
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  Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Oct2010, Vol. 118 Issue 10, p1389-1394. 6p. 1 Chart, 5 Graphs.
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  Data: *<searchLink fieldCode="DE" term="%22Cadmium%22">Cadmium</searchLink><br />*<searchLink fieldCode="DE" term="%22Food+contamination%22">Food contamination</searchLink><br />*<searchLink fieldCode="DE" term="%22Chemical+reactions%22">Chemical reactions</searchLink><br /><searchLink fieldCode="DE" term="%22Estrogen+receptors%22">Estrogen receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Anthropometry%22">Anthropometry</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: BACKGROUND: Cadmium (Cd), a ubiquitous food contaminant, has been proposed to be an endocrine disruptor by inducing estrogenic responses in vivo. Several in vitro studies suggested that these effects are mediated via estrogen receptors (ERs). OBJECTIVE: We performed this study to clarify whether Cd-induced effects in vivo are mediated via classical ER signaling through estrogen responsive element (ERE)-regulated genes or if other signaling pathways are involved. METHODS: We investigated the estrogenic effects of cadmium chloride (CdCl2) exposure in vivo by applying the Organisation for Economic Co-operation and Development (OECD) rodent uterotrophic bioassay to transgenic ERE-luciferase reporter mice. Immature female mice were injected subcutaneously with CdCl2 (5, 50, or 500 µg/kg body weight) or with 17α-ethinylestradiol (EE2) on 3 consecutive days. We examined uterine weight and histology, vaginal opening, body and organ weights, Cd tissue retention, activation of mitogen-activated protein kinase (MAPK) pathways, and ERE-dependent luciferase expression. RESULTS: CdCl2 increased the height of the uterine luminal epithelium in a dose-dependent manner without increasing the uterine wet weight, altering the timing of vaginal opening, or affecting the luciferase activity in reproductive or nonreproductive organs. However, we observed changes in the phosphorylation of mouse double minute 2 oncoprotein (Mdm2) and extracellular signal-regulated kinase (Erk1/2) in the liver after CdCl2 exposure. As we expected, EE2 advanced vaginal opening and increased uterine epithelial height, uterine wet weight, and luciferase activity in various tissues. CONCLUSION: Our data suggest that Cd exposure induces a limited spectrum of estrogenic responses in vivo and that, in certain targets, effects of Cd might not be mediated via classical ER signaling through ERE-regulated genes. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Text: English
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      – SubjectFull: Chemical reactions
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      – TitleFull: Estrogen-Like Effects of Cadmium in Vivo Do Not Appear to be Mediated via the Classical Estrogen Receptor Transcriptional Pathway.
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