Partial thyrocyte-specific Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma–like lesions in mice

What is it about?

Thyroid diseases are common and affect more than 10 % of the population. The thyroid gland produces and secretes hormones, which are essential for health, brain, and growth development. Thyroid dysfunction can be associated with an increased risk of cardiovascular morbidity and mortality, dyslipidemia, obesity, fracture risk, and an elevated lifetime cancer risk. _x000D_ _x000D_ The thyroid is mainly controlled by the thyroid-stimulating hormone (TSH), which binds to its receptor (TSHR) on thyrocytes and mediates its action via different G protein-mediated signaling pathways. Data from the last two decades have shown that TSHR can couple to all G protein families, but it mainly activates the Gs- and Gq/11-mediated signaling cascades. However, there is still a knowledge gap concerning the role of the individual G protein cascades in thyroid pathophysiology and their putative significance in vivo._x000D_ _x000D_ Here, we show, that partial thyrocyte-specific Gαs deficiency leads to rapid onset hypothyroidism and sex-dependent metabolic adaptations using a novel genetically inducible hypothyroidism model. Unexpectedly, a partial thyrocyte-specific Gαs deficiency is also associated with hyperplastic and neoplastic lesions in thyroid. The latter tumor phenotype was demonstrated to develop from a small part of nonrecombined thyrocytes still expressing Gαs in the presence of highly elevated serum TSH.

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