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Cited by 83Effects and risks of endocrine disrupting chemicalsThyroid Disorders and TreatmentsToxic Organic Pollutants Impact

Regulation of thyroid-disrupting chemicals to protect the developing brain

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Gilbert, Mary E, O’Shaughnessy, Katherine L, Axelstad, Marta·2020·Endocrinology
DOI 10.1210/endocr/bqaa106PMC PMC8650774
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Abstract

Synthetic chemicals with endocrine disrupting properties are pervasive in the environment and are present in the bodies of humans and wildlife. As thyroid hormones (THs) control normal brain development, and maternal hypothyroxinemia is associated with neurological impairments in children, chemicals that interfere with TH signaling are of considerable concern for children’s health. However, identifying thyroid-disrupting chemicals (TDCs) in vivo is largely based on measuring serum tetraiodothyronine in rats, which may be inadequate to assess TDCs with disparate mechanisms of action and insufficient to evaluate the potential neurotoxicity of TDCs. In this review 2 neurodevelopmental processes that are dependent on TH action are highlighted, neuronal migration and maturation of gamma amino butyric acid-ergic interneurons. We discuss how interruption of these processes by TDCs may contribute to abnormal brain circuitry following developmental TH insufficiency. Finally, we identify issues in evaluating the developmental neurotoxicity of TDCs and the strengths and limitations of current approaches designed to regulate them. It is clear that an enhanced understanding of how THs affect brain development will lead to refined toxicity testing, reducing uncertainty and improving our ability to protect children’s health.

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  • The close integration of synaptic and endocrine signaling renders the CNS particularly vulnerable to EDCs.

    “This close integration of synaptic and endocrine signaling renders the CNS particularly vulnerable to EDCs, which are exogenous substances or mixtures that interfere with endocrine function and thereby cause adverse effects in exposed organisms or their offspring (Damiano et al., 2025; Gilbert et al., 2020; Klyubin et al., 2022; Schug et al., 2015).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Gilbert et al., 2020

    The Abstract links thyroid-hormone signaling to brain development, and “Synaptic Function in the Hippocampus” reports lasting synaptic effects of developmental thyroid-hormone insufficiency. These passages support vulnerability to thyroid-disrupting chemicals during development, but not the broader claim that close integration of synaptic and endocrine signaling makes the CNS particularly vulnerable to EDCs generally. No page numbers are available in our copy. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Gilbert, M. E., O’Shaughnessy, K. L., & Axelstad, M.
Affiliations
  • Environmental Protection Agency (US)
  • Technical University of Denmark (DK)
Corresponding author
Gilbert, Mary E
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2020-07-02
Volume
161
Issue
10
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endocr/bqaa106
PMC
PMC8650774
OpenAlex
W3039243158
Cited by
83
References
13
Citations by year
2026: 12 · 2025: 14 · 2024: 12 · 2023: 24 · 2022: 12 · 2021: 8 · 2020: 1
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Endocrinology (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Keywords
thyroid disrupting chemicals, endocrine disruptors, thyroid hormones, brain development, developmental neurotoxicity, maternal hypothyroxinemia, neuronal migration, thyroxine, regulatory toxicology, child health
MeSH terms
Animals, Brain, Child, Humans, Thyroid Gland, Neurotoxicity Syndromes, Rats, Endocrine Disruptors, Neurogenesis

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