Comparative analysis of zearalenone effects on thyroid receptor alpha (TRα) and beta (TRβ) expression in rat primary cerebellar cell cultures

Kiss, David; Ioja, Eniko; Toth, Istvan; Barany, Zoltan; Jocsak, Gergely; Bartha, Tibor; Horvath, Tamas; Zsarnovszky, Attila

doi:10.3390/ijms19051440

Cited by 18Mycotoxins in Agriculture and FoodEstrogen and related hormone effectsEffects and risks of endocrine disrupting chemicals

Comparative analysis of zearalenone effects on thyroid receptor alpha (TRα) and beta (TRβ) expression in rat primary cerebellar cell cultures

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Kiss, David, Ioja, Eniko, Toth, Istvan, Barany, Zoltan, Jocsak, Gergely, Bartha, Tibor, Horvath, Tamas, Zsarnovszky, Attila·2018·International Journal of Molecular Sciences

DOI 10.3390/ijms19051440PMC PMC5983839

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Abstract

Thyroid receptors play an important role in postnatal brain development. Zearalenone (ZEN), a major mycotoxin of Fusarium fungi, is well known to cause serious health problems in animals and humans through various mechanisms, including the physiological pathways of thyroid hormone (TH). In the present study, we aimed to investigate the expression of thyroid receptors α (TRα) and β (TRβ) in primary cerebellar neurons in the presence or absence of glia and following ZEN treatment, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Primary cerebellar granule cells were treated with low doses of ZEN (0.1 nM) in combination with physiologically relevant concentrations of l-thyroxine (T4), 3,3',5-triiodo-l-thyronine (T3) and 17β-estradiol (E2). Expression levels of TRα and TRβ at mRNA and protein levels were slightly modified by ZEN administered alone; however, along with thyroid and steroid hormones, modelling the physiological conditions, expression levels of TRs varied highly depending on the given treatment. Gene expression levels were also highly modulated by the presence or absence of glial cells, with mostly contrasting effects. Our results demonstrate divergent transcriptional and translational mechanisms involved in the expression of TRs implied by ZEN and hormonal milieu, as well as culturing conditions.

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Zearalenone (ZEN) can directly interfere with hormonal signaling pathways as a phytoestrogen due to its structural similarity to 17-β-estradiol.
“Among them, zearalenone (ZEN) plays a special role, as it can directly interfere with hormonal signaling pathways as a phytoestrogen due to its structural similarity to 17-β-estradiol (Jocsak et al., 2019; Kiss et al., 2018).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Kiss et al., 2018
The Introduction describes ZEN as an estrogenic mycotoxin that binds estrogen receptors, and the Discussion calls it an endocrine disruptor. The paper does not state that ZEN is a phytoestrogen or that structural similarity to 17β-estradiol explains its effects; the Introduction compares their reported effects, not their structures. Page numbers are unavailable in our copy. (LLM, conf=0.85)
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“Among them, zearalenone (ZEN) plays a special role, as it can directly interfere with hormonal signaling pathways as a phytoestro-gen due to its structural similarity to 17-β -estradiol (Jocsak et al., 2019; Kiss et al., 2018).”
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Authors: Kiss, D., Ioja, E., Toth, I., Barany, Z., Jocsak, G., Bartha, T., Horvath, T., & Zsarnovszky, A.
Affiliations: Department of Physiology and Biochemistry, University of Veterinary Medicine, 1078 Budapest, Hungary
Department of Animal Physiology and Animal Health, Faculty of Agricultural and Environmental Sciences, Szent István University, Páter Károly u. 1, H-2100 Gödöllő, Hungary
University of Veterinary Medicine (HU)
Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Magyar Agrár- és Élettudományi Egyetem (HU)
Corresponding author: Zsarnovszky, Attila
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2018-05-11
Volume: 19
Issue: 5
Pages: 1440
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms19051440
PMC: PMC5983839
OpenAlex: W2802487450
Cited by: 18
References: 104
Citations by year: 2026: 1 · 2025: 6 · 2024: 4 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1
FWCI: 1.33
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Hungarian Scientific Research Fund (104982, 115613)
Topics: Life Sciences › Agricultural and Biological Sciences › Plant Science › Mycotoxins in Agriculture and Food
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords: zearalenone, thyroid receptor alpha, thyroid hormone receptor beta, cerebellar granule cells, mycotoxins, thyroid hormones, levothyroxine, triiodothyronine, estradiol, glial cells, postnatal brain development, gene expression
MeSH terms: Animals, Cerebellum, Estrogens, Non-Steroidal, Gene Expression Regulation, Neurons, Zearalenone, Thyroid Hormone Receptors alpha, Thyroid Hormone Receptors beta, Rats, Primary Cell Culture

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Comparative analysis of zearalenone effects on thyroid receptor alpha (TRα) and beta (TRβ) expression in rat primary cerebellar cell cultures

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