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Cited by 6Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersThyroid Disorders and Treatments

The interplay of the mammalian brain and thyroid hormones, and the threat of endocrine-disrupting chemicals

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Dsouki, Nuha Ahmad, Pereira, Bruno Fiorelini, da Silva, Roberta Goes, Rodrigues, Vinicius Gonçalves, Brito, Rafaella da Silva, Kizys, Marina Malta Letro, Chiamolera, Maria Izabel, Maciel, Rui Monteiro +2 more·2024·Endocrines
DOI 10.3390/endocrines5040036
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Abstract

Introduction: During the formation of neural circuits, the developing brain demonstrates extraordinary plasticity, heavily influenced by hormones. These chemical messengers interact with specific receptors to regulate vital physiological functions. The thyroid gland plays a pivotal role in maintaining hormonal balance and guiding brain development. However, emerging threats like endocrine-disrupting chemicals (EDCs) can interfere with this intricate system. EDCs are exogenous substances that can mimic, enhance, or block the actions of endogenous hormones, disrupting hormonal signaling in the brain at various developmental stages. Exposure can impair cognitive function and behavior due to disruptions in thyroid function. Studies indicate that mixtures of EDCs negatively impact brain development, leading to lower IQ and behavioral problems. Reducing EDC exposure through regulations and public awareness is crucial, and further research is needed to elucidate their mechanisms. Conclusions: Protecting vulnerable populations, such as pregnant women and children, is essential through prompt regulatory measures.

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  • Sex steroids, thyroid hormones, and glucocorticoids modulate synaptic transmission, dendritic spine dynamics, neuronal excitability, and circuit maturation, particularly in the hippocampus and hypothalamus.

    “Sex steroids, thyroid hormones, and glucocorticoids modulate synaptic transmission, dendritic spine dynamics, neuronal excitability, and circuit maturation, particularly in plasticity-relevant regions such as the hippocampus and hypothalamus (Damiano et al., 2025; Dos-Santos et al., 2023; Dsouki et al., 2024; Ogiue-Ikeda et al., 2008; Pang and Han, 2012; Parent et al., 2011; Weiss, 2007).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dsouki et al., 2024

    Section 1.1.5 reports that thyroid-hormone imbalances may alter synaptic development and that hypothyroidism affects hippocampal neurogenesis; section 1.1.3 discusses thyroid-hormone receptors in the hypothalamus. This supports the thyroid-hormone and brain-development portion of the multi-cited sentence, but the cited paper does not establish the specific claims about dendritic spine dynamics or neuronal excitability. It also does not address the sex-steroid or glucocorticoid portions. (LLM, conf=0.86)

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  • PCBs reduce circulating thyroxine, interfere with hepatic and cerebral thyroid hormone metabolism, compete with T4 for binding to transthyretin, and can interact directly with thyroid hormone receptors, acting in a context-dependent agonistic or antagonistic manner.

    “PCBs reduce circulating thyroxine, interfere with hepatic and cerebral thyroid hormone metabolism, compete with thyroxine (T4) for binding to transthyretin, and can interact directly with thyroid hormone receptors, acting in a context-dependent agonistic or antagonistic manner [a8] (Dsouki et al., 2024; Schug et al., 2015; Zoeller et al., 2000).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dsouki et al., 2024

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  • PBDEs are persistent and lipophilic, and due to regulatory restrictions are increasingly replaced by OPFRs, which are not harmless.

    “Among the most prominent representatives are polybrominated diphenyl ethers (PBDEs), which are characterized by their persistence and lipophilic nature. Due to regulatory restrictions, PBDEs are increasingly being replaced by organophosphate flame retardants (OPFRs), which are by no means harmless (Damiano et al., 2025; Dsouki et al., 2024; Rojas et al., 2025).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dsouki et al., 2024

    The PBDEs section (page not provided) says certain PBDE congeners have been prohibited in Europe and some U.S. states but remain prevalent because of their long half-lives, supporting the persistence and regulatory-restriction points. It does not describe PBDEs as lipophilic or say they are increasingly replaced by organophosphate flame retardants (OPFRs), or assess OPFRs' safety. The paper's discussion of organophosphates concerns pesticides, not flame retardants. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Dsouki, N. A., Pereira, B. F., da Silva, R. G., Rodrigues, V. G., Brito, R. D. S., Kizys, M. M. L., Chiamolera, M. I., Maciel, R. M., Serrano-Nascimento, C., & Giannocco, G.
Affiliations
  • Universidade Federal de São Paulo (BR)
  • Laboratório de Endocrinologia Molecular e Translacional, Departamento de Medicina, Universidade Federal de São Paulo, UNIFESP, São Paulo 04039-032, SP, Brazil
  • Instituto de Ciências Ambientais, Químicas e Farmacêuticas (BR)
Corresponding author
Giannocco, Gisele
ORCID
Venue
Endocrines
Publisher
MDPI AG
Published
2024-10-25
Volume
5
Issue
4
Pages
501-515
ISSN
2673-396X (ISSN-L)
DOI
10.3390/endocrines5040036
OpenAlex
W4403762863
Cited by
6
References
7
Citations by year
2026: 2 · 2025: 4
FWCI
1.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrines (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • São Paulo Research Foundation (FAPESP) (2022/03094-5, 2021/02752-6, 2022/10804-9, 2016/18517-8, 406643/2022-9, 405825/2021-8, 406997/2023-3)
  • Brazilian National Council for Scientific and Technological Development (CNPq) (2022/03094-5, 2021/02752-6, 2022/10804-9, 2016/18517-8, 406643/2022-9, 405825/2021-8, 406997/2023-3)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Keywords
thyroid hormones, endocrine disruptors, brain development, neuroplasticity, hormone signaling, cognitive function, behavioral problems, IQ, chemical mixtures, prenatal exposure, children, pregnant women, hormonal regulation, chemical regulation

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