Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production

• DOI: 10.1172/jci.insight.149425
• Publication Date: 2021-07-08T16:02:30Z
• Authors: Sujie Ke; Yan-Yun Liu; Rajendiran Karthi...; Kurunthachalam Ka...; Jingjing Jiang; Kiyomi Abe; Anna Milanesi; Gregory A. Brent
• Keywords: Thyroid hormone receptor; Thyroglobulin

Thyroid hormone receptor β (THRB) is posttranslationally modified by small ubiquitin-like modifier (SUMO). We generated a mouse model with mutation that disrupted sumoylation at lysine 146 (K146Q) and resulted in desumoylated THRB as the predominant form tissues. The K146Q mutant mice had normal serum thyroxine (T4), markedly elevated thyrotropin-stimulating (TSH; 81-fold above control), enlargement of both pituitary thyroid gland. marked elevation TSH, despite T4, indicated blunted feedback regulation TSH. altered recruitment transcription factors to TSHβ gene promoter, compared WT, hyperthyroidism hypothyroidism. content (T4, T3, rT3) gland was 10-fold lower (per gram tissue) than control, TSH bioactivity. expression thyroglobulin dual oxidase 2 genes reduced associated modifications cAMP response element-binding protein DNA binding cofactor interactions presence THRB. Therefore, production TSH-dependent TSH-independent components. conclude K146 required for TH synthesis gland, pathway.