Thyroid in a jar: towards an integrated in vitro testing strategy for thyroid-active compounds

B. Jomaa

Research output: Thesisinternal PhD, WUAcademic

Abstract

 

Jomaa, B. (2015). Thyroid in a Jar: Towards an Integrated In Vitro Testing Strategy for Thyroid-Active Compounds. PhD thesis, Wageningen University, the Netherlands

Abstract

The aim of this thesis was to find in vitro and toxicogenomics-based alternatives to in vivo thyroid hormone disruption tests. In vitro alternatives can help reduce the amount of animal testing required under the European Union regulation for the registration, evaluation, authorization and restriction of chemicals (REACH). Moreover, with the use of human cell lines and human-identical synthetic proteins, interspecies differences can be reduced and in some cases eliminated. This thesis has shed light on the relevance of current in vitro assays for thyroid and pituitary cell proliferation, has led to the development of the TSH screen, a luminol-based thyroid peroxidase inhibition assay and the zebrafish-based general development score (GDS) for the detection of developmental toxicants, including those that act through the thyroid hormone system. Moreover, the microarray assay for real-time coregulator-nuclear receptor interaction (MARCoNI) assay was used to reveal the modulating effects of thyroid-active compounds on TRα and TRβ interactions with a peptide array representing 66 different coregulators. These developments along with an in-depth analysis of the thyroid hormone system and the presentation of the state of the art in thyroid disruption testing have highlighted the progress made and at the same time have underlined the challenges that lay ahead.

LanguageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Rietjens, Ivonne, Promotor
  • Aarts, Jac, Co-promotor
  • Peijnenburg, Ad, Co-promotor
Award date5 Jun 2015
Place of PublicationWageningen
Publisher
Print ISBNs9789090290089
Publication statusPublished - 2015

Fingerprint

Thyroid Gland
Thyroid Hormones
Toxicogenetics
Luminol
Iodide Peroxidase
Zebrafish
European Union
Cytoplasmic and Nuclear Receptors
Netherlands
Cell Proliferation
In Vitro Techniques
Cell Line
Peptides
Proteins

Keywords

  • thyroid diseases
  • thyroid hormones
  • endocrine disruptors
  • in vitro
  • assays
  • cell growth

Cite this

Jomaa, B.. / Thyroid in a jar: towards an integrated in vitro testing strategy for thyroid-active compounds. Wageningen : Wageningen University, 2015. 187 p.
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Jomaa, B 2015, 'Thyroid in a jar: towards an integrated in vitro testing strategy for thyroid-active compounds', Doctor of Philosophy, Wageningen University, Wageningen.

Thyroid in a jar: towards an integrated in vitro testing strategy for thyroid-active compounds. / Jomaa, B.

Wageningen : Wageningen University, 2015. 187 p.

Research output: Thesisinternal PhD, WUAcademic

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AB -   Jomaa, B. (2015). Thyroid in a Jar: Towards an Integrated In Vitro Testing Strategy for Thyroid-Active Compounds. PhD thesis, Wageningen University, the Netherlands Abstract The aim of this thesis was to find in vitro and toxicogenomics-based alternatives to in vivo thyroid hormone disruption tests. In vitro alternatives can help reduce the amount of animal testing required under the European Union regulation for the registration, evaluation, authorization and restriction of chemicals (REACH). Moreover, with the use of human cell lines and human-identical synthetic proteins, interspecies differences can be reduced and in some cases eliminated. This thesis has shed light on the relevance of current in vitro assays for thyroid and pituitary cell proliferation, has led to the development of the TSH screen, a luminol-based thyroid peroxidase inhibition assay and the zebrafish-based general development score (GDS) for the detection of developmental toxicants, including those that act through the thyroid hormone system. Moreover, the microarray assay for real-time coregulator-nuclear receptor interaction (MARCoNI) assay was used to reveal the modulating effects of thyroid-active compounds on TRα and TRβ interactions with a peptide array representing 66 different coregulators. These developments along with an in-depth analysis of the thyroid hormone system and the presentation of the state of the art in thyroid disruption testing have highlighted the progress made and at the same time have underlined the challenges that lay ahead.

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KW - assays

KW - cell growth

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