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Expression data for hindlimb and tail samples in a metamorphosis assay for thyroid axis disruption - inhibitors

ABSTRACT: Thyroid hormones (TH), thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3), play crucial roles in regulation of growth, development and metabolism in vertebrates and are targets for endocrine disruptive agents. Perturbations in TH action can contribute to the development of disease states and the U.S. Environmental Protection Agency is developing a high throughput screen using TH-dependent metamorphosis of the Xenopus laevis tadpole as an assay platform. Currently this methodology relies on external morphological endpoints and changes in central thyroid axis parameters. However, exposure-related changes in gene expression in TH-sensitive tissue types that occur over shorter time frames have the potential to augment this screen. Using a combination of cDNA array and real time quantitative polymerase chain reaction (QPCR) analyses, this study identifies molecular markers in tissues peripheral to the central thyroid axis. We examine the hindlimb and tail of tadpoles up to 96 hours of continuous exposure to T3, T4, methimazole, propylthiouracil, or perchlorate. Several novel biomarker candidates are indicated that include transcripts encoding importin, RNA helicase II/Gu, and defender against death protein, DAD1. In combination with previously-identified biomarker candidates, these transcripts will greatly augment the predictive and diagnostic power of the Xenopus metamorphosis assay for perturbation of TH action. Keywords: time course

ORGANISM(S): Xenopus laevis Aquarana catesbeiana

PROVIDER: GSE7051 | GEO | 2007/05/12

SECONDARY ACCESSION(S): PRJNA98515

REPOSITORIES: GEO

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Expression data for brain samples in a metamorphosis assay for thyroid axis disruption

Project description:Thyroid hormones (TH), thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3), play crucial roles in regulation of growth, development and metabolism in vertebrates and their action are targets for endocrine disruptive agents. Perturbations in TH action can contribute to the development of disease states and the U.S. Environmental Protection Agency is developing a high throughput screen using TH-dependent amphibian metamorphosis as an assay platform. Currently this methodology relies on external morphological endpoints and changes in central thyroid axis parameters. However, exposure-related changes in gene expression in TH-sensitive tissue types that occur over shorter time frames have the potential to augment this screen. This study aims to characterize and identify molecular markers in the tadpole brain. Using a combination of cDNA array analysis and real time quantitative polymerase chain reaction (QPCR), we examine the brain of tadpoles following 96 hours of continuous exposure to T3, T4, methimazole, propylthiouracil, or perchlorate. This tissue was more sensitive to T4 rather than T3, even when differences in biological activity were taken into account. This implies that a simple conversion of T4 to T3 cannot fully account for T4 effects on the brain and suggests distinctive mechanisms of action for the two THs. While the brain shows gene expression alterations for methimazole and propylthiouracil, the environmental contaminant, perchlorate, had the greatest effect on the levels of mRNAs encoding proteins important in neural development and function. Our data identify gene expression profiles that can serve as exposure indicators of these chemicals. Keywords: dose response

2007-05-12 | GSE7057 | GEO

Expression data for brain samples in a metamorphosis assay for thyroid axis disruption - inhibitors

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Expression data from stage 54 Xenopus laevis larvae treated with 20 nM triiodothyronine (T3)

Project description:Induction of Xenopus laevis larvae metamorphosis is dependent on exposure to TH. Metamorphosis involves the regression, growth or remodeling of almost all the tissues in the animals body. Metamorphosis in frogs is induced by thyroid hormone. Each organ system has a unique morphological and genetic program that it follows while undergoing metamorphosis involving both the upregulation and downregulation of genes. In this array we examined the change in gene expression in the tail of larvae undergoing precocious metamorphosis following induction with thyroid hormone. Whole stage 54 xenopus larvae were exposed to either vehicle for 48 hours or 20 nM T3 for 6 or 48 hours. Total RNA was then purified from tail tissue and the samples were examined by hybridization to the Affymetrix Xenopus array. Developmental stage 51-54 Xenopus larvae were selected because these stages do not express high levels of endogenous T3 but are still capable of morphologically responding to exposure.

2010-07-30 | E-GEOD-22643 | biostudies-arrayexpress

Brain gene expression in systemic hypothyroidism and in mouse models of MCT8 deficiency: The Mct8-Oatp1c1-Dio2 triad.

Project description:The monocarboxylate transporter 8 (Mct8) protein is a primary T4 and T3 (TH) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alters thyroid function and thyroid hormone metabolism, and severely impairs neurodevelopment (Allan-Herndon-Dudley syndrome, AHDS). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is thought that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase (D2). The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knock out mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, would be more approriate models of AHDS. The goal of this work was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KOs.

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Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part B

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2010-05-16 | E-GEOD-16017 | biostudies-arrayexpress

Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part C

Project description:Thyroid hormone (TH) controls the remodeling of the pancreas and the liver. TH-induces dedifferentiation of the exocrine pancreas to a progenitor state (Proc. Nat. Acad Sci. 105, 8962-8967 (2008)) and it remodels the endocrine pancreas (Dev. Biol. 328, 384-391 (2009)). The redifferentiated frog pancreas resembles closely the pancreas of other typical vertebrates. Two pancreas arrays were carried out. The first one studied gene expression changes at different developmental stages of Xenopus laevis during metamorphosis. The second array studies gene expression changes at varying times after the addition of TH to premetamorphic tadpoles. Keywords: co-expression design,development or differentiation design,reference design,time series design Overall design: Thyroid hormone (TH) controls remodeling of the pancreas. The microarray was carried out to identify changes in gene expression at different stages of development during metamorphosis.. This is part 3, done on the 22K Xenopus platform version 2. This dataset was from pancreas of Xenopus tadpoles (NF52, NF62, and NF66). Each was made in triplicate. Samples in all 3 parts of the study received the same thyroid hormone levels.

2010-05-16 | E-GEOD-16018 | biostudies-arrayexpress

Expression data from stage 54 Xenopus laevis larvae treated with 20 nM triiodothyronine (T3)

2010-07-01 | GSE22643 | GEO

Transcription profiling of brains, hindlimbs and tails of Xenopus laevis tadpoles after treatment with thyroid hormone

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2006-11-08 | E-MNIA-94 | biostudies-arrayexpress

Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part A

Project description:Thyroid hormone (TH) controls the remodeling of the pancreas and the liver. TH-induces dedifferentiation of the exocrine pancreas to a progenitor state (Proc. Nat. Acad Sci. 105, 8962-8967 (2008)) and it remodels the endocrine pancreas (Dev. Biol. 328, 384-391 (2009)). The redifferentiated frog pancreas resembles closely the pancreas of other typical vertebrates. Two pancreas arrays were carried out. The first one studied gene expression changes at different developmental stages of Xenopus laevis during metamorphosis. The second array studies gene expression changes at varying times after the addition of TH to premetamorphic tadpoles. Keywords: cell cycle design,co-expression design,reference design,time series design Thyroid hormone (TH) controls remodeling of the pancreas. The micro array was carried out to identify changes in gene expression between the tadpole and frog pancreas. This is part 1, done on the 44K Xenopus platform. This dataset was used only for one pancreas experiment with several data points (control, 12h, 24h, 48h and frog). Each was made in triplicate. Samples in all 3 parts of the study received the same thyroid hormone levels.

2010-05-16 | E-GEOD-16074 | biostudies-arrayexpress

Thyroid hormone induced resorption of tail in Xenopus laevis tadpole

Project description:Premetamorphic Xenopus laevis tadpole tail respond to thyroid hormone by resorption. The goal of this experiment is to identify the genes involved in the TH-induced resorption tadpole tail and compare it to TH-induced proliferation and differentiation program in tadpole limb and brain. Xenopus tadpoles (NF54) were treated with 100 nM T3 in 0.1 x MMR for another 24h and 48h or without T3 for 48h (control group). NF 61 tadpoles were in 0.1 X MMR till they reached NF stage 62. The tails were dissected after the experiment. Keywords: development or differentiation design,organism part comparison design,reference design,replicate design,time series design

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