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
Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
iScience. 2024 Dec 10;28(1):111565. doi: 10.1016/j.isci.2024.111565. eCollection 2025 Jan 17.
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, was exclusively upregulated with TSH overexpression among genes crucial to thyroid hormone secretion. To verify its significance, we overexpressed TSH in knockout mice. TSH overexpression caused hyperthyroidism in 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.
促甲状腺激素受体(TSHR)的激活从根本上导致甲状腺功能亢进。为了阐明TSHR信号传导,我们对通过过度表达TSH产生的甲状腺功能亢进小鼠进行了转录组分析。TSH的过度表达极大地改变了它们的甲状腺转录组。特别是,富集分析确定细胞周期、磷脂酰肌醇3-激酶/蛋白激酶B途径和Ras相关蛋白1途径可能与甲状腺肿的发展有关。关于甲状腺功能亢进,在对甲状腺激素分泌至关重要的基因中, 仅在TSH过度表达时上调。为了验证其重要性,我们在 基因敲除小鼠中过度表达TSH。TSH的过度表达在 基因敲除小鼠中引起了甲状腺功能亢进,与对照小鼠相当。因此,我们没有观察到TSH过度表达时甲状腺激素分泌相关的已知基因和途径有显著变化。我们的数据集可能包括尚未被鉴定为甲状腺功能调节因子的候选基因。我们关于甲状腺功能亢进的转录组数据集可以为未来TSHR信号传导的研究做出贡献。