Transcriptomic landscape of hyperthyroidism in mice overexpressing thyroid-Stimulating hormone

Activation of thyroid-stimulating hormone receptor (TSHR) fundamentally leads to hyperthyroidism. To elucidate TSHR signaling, we conducted transcriptome analyses for hyperthyroid mice that we generated by overexpressing TSH. TSH overexpression drastically changed their thyroid transcriptome. In par...

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Bibliographic Details
Published in:iScience 2025-01, Vol.28 (1), Article 111565
Main Authors: Yamauchi, Ichiro, Sugawa, Taku, Hakata, Takuro, Yoshizawa, Akira, Kita, Tomoko, Kishimoto, Yo, Kimura, Sadahito, Sakurai, Aya, Kosugi, Daisuke, Fujita, Haruka, Okamoto, Kentaro, Ueda, Yohei, Fujii, Toshihito, Taura, Daisuke, Sakane, Yoriko, Yasoda, Akihiro, Inagaki, Nobuya
Format: Article
Language:English
Subjects:
Endocrine system physiology
Endocrinology
Model organism
Transcriptomics
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Summary:Activation of thyroid-stimulating hormone receptor (TSHR) fundamentally leads to hyperthyroidism. To elucidate TSHR signaling, we conducted transcriptome analyses for hyperthyroid mice that we generated by overexpressing TSH. TSH overexpression drastically changed their thyroid transcriptome. In particular, enrichment analyses identified the cell cycle, phosphatidylinositol 3-kinase/Akt pathway, and Ras-related protein 1 pathway as possibly associated with goiter development. Regarding hyperthyroidism, Slc26a4 was exclusively upregulated with TSH overexpression among genes crucial to thyroid hormone secretion. To verify its significance, we overexpressed TSH in Slc26a4 knockout mice. TSH overexpression caused hyperthyroidism in Slc26a4 knockout mice, equivalent to that in control mice. Thus, we did not observe significant changes in known genes and pathways involved in thyroid hormone secretion with TSH overexpression. Our datasets might include candidate genes that have not yet been identified as regulators of thyroid function. Our transcriptome datasets regarding hyperthyroidism can contribute to future research on TSHR signaling. [Display omitted] •We generated mice overexpressing thyroid-stimulating hormone (TSH) via gene delivery•These mice exhibited hyperthyroidism and goiters•TSH overexpression drastically changed their thyroid transcriptome•Our transcriptome datasets can contribute to future research on hyperthyroidism Endocrine system physiology; Endocrinology; Transcriptomics; Model organism
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.111565