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 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. Our hyperthyroid mice exhibited excessive secretion of thyroid hormones and goiter development through the effects of TSH overexpression. Using this model, we subsequently obtained data on the thyroid transcriptome using RNA-seq. Empty = mice injected with pLIVE-Empty vector TSH = mice overexpressing TSH by injecting with pLIVE-TSHB and pLIVE-CGA vectors TSH-MMI = mice overexpressing TSH that were treated with thiamazole (MMI) Empty-MMI = mice injected with pLIVE-Empty vector that were treated with MMI more details in bioRxiv 2023.10.27.564354.