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Toxicol Sci
2018 Jan 01;1611:196-206. doi: 10.1093/toxsci/kfx213.
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Dioxin Exposure Alters Molecular and Morphological Responses to Thyroid Hormone in Xenopus laevis Cultured Cells and Prometamorphic Tadpoles.
Taft JD, Colonnetta MM, Schafer RE, Plick N, Powell WH.
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Amphibian metamorphosis is driven by thyroid hormone (TH). We used prometamorphic tadpoles and a cell line of the African clawed frog (Xenopus laevis) to examine immediate effects of dioxin exposure on TH. Gene expression patterns suggest cross-talk between the thyroid hormone receptor (TR) and aryl hydrocarbon receptor (AHR) signaling pathways. In XLK-WG cells, expression of Cytochrome P450 1A6 (cyp1A6), an AHR target, was induced 1000-fold by 100 nM TCDD (2, 3, 7, 8 tetrachlorodibenzo-p-dioxin). Krüppel-Like Factor 9 (klf9), the first gene induced in a cascade of TH responses tied to metamorphosis, was upregulated over 5-fold by 50 nM triiodothyronine (T3) and 2-fold by dioxin. Co-exposure to T3 and TCDD boosted both responses, further inducing cyp1A6 by 75% and klf9 about 60%. Additional canonical targets of each receptor, including trβa and trβb (TR) and udpgt1a (AHR) responded similarly. Induction of TH targets by TCDD in XLK-WG cells predicts that exposure could speed metamorphosis. We tested this hypothesis in two remodeling events: tail resorption and hind limb growth. Resorption of ex vivo cultured tails was accelerated by 10 nM T3, while a modest increase in resorption by 100 nM TCDD lacked statistical significance. Hind limbs doubled in length over four days following 1 nM T3 treatment, but limb length was unaffected by 100 nM TCDD. TCDD co-exposure reduced the T3 effect by nearly 40%, despite TCDD induction of klf9 in whole tadpoles, alone or with T3. These results suggest that tissue-specific TCDD effects limit or reverse the increased metamorphosis rate predicted by klf9 induction.
Bagamasbad,
Deciphering the regulatory logic of an ancient, ultraconserved nuclear receptor enhancer module.
2015, Pubmed,
Xenbase
Bagamasbad,
Deciphering the regulatory logic of an ancient, ultraconserved nuclear receptor enhancer module.
2015,
Pubmed
,
Xenbase Bagamasbad,
Molecular basis for glucocorticoid induction of the Kruppel-like factor 9 gene in hippocampal neurons.
2012,
Pubmed Beatty,
Toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in larval and adult forms of Rana catesbeiana.
1976,
Pubmed Beischlag,
ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription.
2005,
Pubmed Boitano,
Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells.
2010,
Pubmed Bonett,
Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis.
2010,
Pubmed
,
Xenbase Brown,
Amphibian metamorphosis.
2007,
Pubmed
,
Xenbase Brown,
Amphibian metamorphosis: a complex program of gene expression changes controlled by the thyroid hormone.
1995,
Pubmed
,
Xenbase Buchholz,
Molecular and developmental analyses of thyroid hormone receptor function in Xenopus laevis, the African clawed frog.
2006,
Pubmed
,
Xenbase Buchholz,
More similar than you think: Frog metamorphosis as a model of human perinatal endocrinology.
2015,
Pubmed
,
Xenbase Chan,
Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways. Demonstration of competition and compensation.
1999,
Pubmed Choi,
Unliganded thyroid hormone receptor α regulates developmental timing via gene repression in Xenopus tropicalis.
2015,
Pubmed
,
Xenbase Choi,
Growth, Development, and Intestinal Remodeling Occurs in the Absence of Thyroid Hormone Receptor α in Tadpoles of Xenopus tropicalis.
2017,
Pubmed
,
Xenbase Collier,
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the mortality and growth of two amphibian species (Xenopus laevis and Pseudacris triseriata).
2008,
Pubmed
,
Xenbase Crofton,
Thyroid disrupting chemicals: mechanisms and mixtures.
2008,
Pubmed Dell'Orto,
Cellular targets in response to dioxin exposure.
1998,
Pubmed
,
Xenbase Freeburg,
Subfunctionalization of Paralogous Aryl Hydrocarbon Receptors from the Frog Xenopus Laevis: Distinct Target Genes and Differential Responses to Specific Agonists in a Single Cell Type.
2017,
Pubmed
,
Xenbase Furlow,
A developmental switch induced by thyroid hormone: Xenopus laevis metamorphosis.
2006,
Pubmed
,
Xenbase Furlow,
The transcription factor basic transcription element-binding protein 1 is a direct thyroid hormone response gene in the frog Xenopus laevis.
2002,
Pubmed
,
Xenbase Furlow,
Induction of larval tissue resorption in Xenopus laevis tadpoles by the thyroid hormone receptor agonist GC-1.
2004,
Pubmed
,
Xenbase Gutleb,
Effects of oral exposure to polychlorinated biphenyls (PCBs) on the development and metamorphosis of two amphibian species (Xenopus laevis and Rana temporaria).
2000,
Pubmed
,
Xenbase Gutleb,
Delayed effects of environmentally relevant concentrations of 3,3',4,4'-tetrachlorobiphenyl (PCB-77) and non-polar sediment extracts detected in the prolonged-FETAX.
2007,
Pubmed
,
Xenbase Hahn,
Diversity as Opportunity: Insights from 600 Million Years of AHR Evolution.
2017,
Pubmed Harrill,
Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice.
2013,
Pubmed Hood,
Differential effects of microsomal enzyme inducers on in vitro thyroxine (T(4)) and triiodothyronine (T(3)) glucuronidation.
2000,
Pubmed Huff,
Long-term carcinogenesis studies on 2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins.
1991,
Pubmed Iwamoto,
Induction of cytochrome P450 family 1 mRNAs and activities in a cell line from the frog Xenopus laevis.
2012,
Pubmed
,
Xenbase Kanamori,
The regulation of thyroid hormone receptor beta genes by thyroid hormone in Xenopus laevis.
1992,
Pubmed
,
Xenbase Kawahara,
Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis.
1991,
Pubmed
,
Xenbase Kulkarni,
Beyond synergy: corticosterone and thyroid hormone have numerous interaction effects on gene regulation in Xenopus tropicalis tadpoles.
2012,
Pubmed
,
Xenbase Lans,
Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzofurans with human transthyretin.
1993,
Pubmed Lans,
Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs.
1994,
Pubmed Laub,
Responsiveness of a Xenopus laevis cell line to the aryl hydrocarbon receptor ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
2010,
Pubmed
,
Xenbase Lavine,
Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
2005,
Pubmed
,
Xenbase Matthews,
Estrogen receptor and aryl hydrocarbon receptor signaling pathways.
2006,
Pubmed Matthews,
Aryl hydrocarbon receptor-mediated transcription: ligand-dependent recruitment of estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters.
2005,
Pubmed Miyata,
Thyroid Hormone-disrupting Effects and the Amphibian Metamorphosis Assay.
2012,
Pubmed
,
Xenbase Nebert,
Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis.
2000,
Pubmed Nishimura,
Disruption of thyroid hormone homeostasis at weaning of Holtzman rats by lactational but not in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
2005,
Pubmed Nishimura,
Rat thyroid hyperplasia induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
2003,
Pubmed Odio,
Specific ligand binding domain residues confer low dioxin responsiveness to AHR1β of Xenopus laevis.
2013,
Pubmed
,
Xenbase Ohtake,
Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.
2003,
Pubmed Patrick,
Thyroid disruption: mechanism and clinical implications in human health.
2009,
Pubmed Philips,
Developmental differences in elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during Xenopus laevis development.
2006,
Pubmed
,
Xenbase Potter,
Thyroid status and thermogenesis in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
1986,
Pubmed Quandt,
MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data.
1995,
Pubmed Roth,
Activity of thyroid hormone-inducible enzymes following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
1988,
Pubmed Sachs,
Frogs model man: In vivo thyroid hormone signaling during development.
2017,
Pubmed
,
Xenbase Sakamoto,
A morphological study of liver lesions in Xenopus larvae exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with special reference to apoptosis of hepatocytes.
1995,
Pubmed
,
Xenbase Sakamoto,
Apoptotic cell death of erythrocytes in Xenopus larvae exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
1997,
Pubmed
,
Xenbase Sany,
Integrated ecological risk assessment of dioxin compounds.
2015,
Pubmed Schapira,
Discovery of diverse thyroid hormone receptor antagonists by high-throughput docking.
2003,
Pubmed Schneider,
NIH Image to ImageJ: 25 years of image analysis.
2012,
Pubmed Sewall,
Alterations in thyroid function in female Sprague-Dawley rats following chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
1995,
Pubmed Smirnova,
Evidence for New Light-Independent Pathways for Generation of the Endogenous Aryl Hydrocarbon Receptor Agonist FICZ.
2016,
Pubmed Tata,
Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone.
1998,
Pubmed Tata,
Amphibian metamorphosis as a model for the developmental actions of thyroid hormone.
2006,
Pubmed
,
Xenbase Tavakoly Sany,
Dioxin risk assessment: mechanisms of action and possible toxicity in human health.
2015,
Pubmed Tian,
Ah receptor and NF-kappaB interplay on the stage of epigenome.
2009,
Pubmed Visser,
Pathways of thyroid hormone metabolism.
1996,
Pubmed Vogel,
A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family.
2009,
Pubmed Vrzal,
Activated thyroid hormone receptor modulates dioxin-inducible aryl hydrocarbon receptor-mediated CYP1A1 induction in human hepatocytes but not in human hepatocarcinoma HepG2 cells.
2017,
Pubmed Wen,
Thyroid Hormone Receptor α Controls Developmental Timing and Regulates the Rate and Coordination of Tissue-Specific Metamorphosis in Xenopus tropicalis.
2017,
Pubmed
,
Xenbase Wincent,
The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans.
2009,
Pubmed Wong,
A role for nucleosome assembly in both silencing and activation of the Xenopus TR beta A gene by the thyroid hormone receptor.
1995,
Pubmed
,
Xenbase Yamada-Okabe,
2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor.
2004,
Pubmed
