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Neural cell screening models for endocrine disruption of thyroid hormone signaling

Thyroid hormone is crucial for proper brain development. Transmembrane thyroid hormone transport, intracellular deiodination and binding of T3 to the thyroid hormone receptor determine thyroid hormone action in target tissues. Chemical exposure can disrupt these intracellular mechanisms, thereby negatively influencing thyroid hormone homeostasis in the brain. To understand how chemicals affect thyroid hormone homeostasis and brain development, new screening methods are needed. We used different human-based in vitro assays to screen endocrine disrupting chemicals (EDCs) for their capacity to disrupt thyroid hormone homeostasis in the brain. Human cell lines representing astrocytes (H4), oligodendrocytes (MO3.13) and neurons (SK-N-AS) were used. Thyroid hormone transport and deiodinase-mediated metabolism were tested using 1 nM radiolabeled thyroid hormone; thyroid hormone receptor activation was measured using qPCR of the T3-responsive gene KLF9. Twelve EDCs were tested, of which six were reference compounds used for validation and six were test compounds.

Details
Type
study
Internal ID
S-VHPS22
Release date
2026-05-27
Version
—
License
CC-BY
URL
https://www.ebi.ac.uk/biostudies/studies/S-VHPS22
DOI
10.6019/S-VHPS22
Publications

No linked publications available.

Files

No files listed.

Authors
  • Nathalie Dierichs
    National Institute for Public Health and the Environment (RIVM), Centre for Health Protection, Bilthoven
    ORCID iD 0009-0000-5074-6239
  • W. Edward Visser
    Erasmus MC University Medical Centre, Rotterdam
    ORCID iD 0000-0002-5248-863X
  • Max Tio
    Erasmus MC University Medical Centre, Rotterdam
    ORCID iD 0009-0001-9438-5508
  • Daniëlle Westerbeek
    Erasmus MC University Medical Centre, Rotterdam
    ORCID iD 0000-0001-6004-8653
  • Aldert Piersma
    National Institute for Public Health and the Environment (RIVM), Centre for Health Protection, Bilthoven
    ORCID iD 0000-0002-1943-7793
  • Ellen Hessel
    National Institute for Public Health and the Environment (RIVM), Centre for Health Protection, Bilthoven
    ORCID iD 0000-0003-3960-7523
  • Robin Peeters
    Erasmus MC University Medical Centre, Rotterdam
    ORCID iD 0000-0001-7732-9371
  • Marcel Erwin Meima
    Erasmus MC University Medical Centre, Rotterdam
    ORCID iD 0000-0002-5392-0519
Funding
  • Dutch Research Agenda (NWA)
    1292.19.272
SK-N-AS
RRID: CVCL_1700 · Supplier: ATCC
Homo sapiens · Brain · Neural tissue · Neuron

Human neuroblastoma cell line used as a neuronal model.

H4
RRID: CVCL_1239 · Supplier: ATCC
Homo sapiens · Brain · Neural tissue · Astrocyte

Human neuroglioma cell line used as an astrocyte model.

MO3.13
RRID: CVCL_D357 · Supplier: Cedarlane Laboratories
Homo sapiens · Brain · Neural tissue · Oligodendrocyte

Human oligodendrocyte cell line.

Exposure duration: 10 minutes
Exposure type: single · Exposure-measurement interval: 0 minutes
Bioassays: Thyroid hormone uptake
Exposure duration: 120 minutes
Exposure type: single · Exposure-measurement interval: 0 minutes
Bioassays: Deiodinase activity (D3)
Exposure duration: 24 hours
Exposure type: single · Exposure-measurement interval: 0 minutes
Bioassays: Whole-cell thyroid hormone metabolism
Exposure duration: 24 hours
Exposure type: single · Exposure-measurement interval: 0 minutes
Bioassays: T3-responsive gene expression (KLF9)
Bioassays
AOP Linkage

Coming soon: normalization, model fitting, statistics, QC, etc.

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Thyroid Question 2 Toxicodynamics