Partial thyrocyte‐specific Gα s deficiency leads to rapid‐onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma‐like lesions in mice

Thyroid function is controlled by thyroid‐stimulating hormone (TSH), which binds to its G protein‐coupled receptor [thyroid‐stimulating hormone receptor (TSHR)] on thyrocytes. TSHR can potentially couple to all G protein families, but it mainly activates the G s ‐ and G q/11 ‐mediated signaling cascades. To date, there is a knowledge gap concerning the role of the individual G protein cascades in thyroid pathophysiology. Here, we demonstrate that the thyrocyte‐specific deletion of G s protein α subunit (Gαs) in adult mice [tamoxifen‐inducible G s protein a subunit deficient (iTGα s KO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGa s KO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGα s KO mice. Unexpectedly, hyperplastic follicles and papillary thyroid cancer‐like tumor lesions with increased proliferation and slightly increased phospho‐ERK1/2 staining were found in iTGα s KO mice at an older age. These tumors developed from nonrecombined thyrocytes still expressing Gα s in the presence of highly elevated serum TSH. In summary, we report that partial thyrocyte‐specific Gα s deletion leads to hypothyroidism but also to tumor development in thyrocytes with remaining Gα s expression. Thus, these mice are a novel model to elucidate the patho physiological consequences of hypothyroidism and TSHR/G

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here