Partial thyrocyte‐specific Gαs deficiency leads to rapid‐onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma‐like lesions in mice. Issue 11 (25th May 2018)

• Record Type: Journal Article
• Authors: Patyra, Konrad; Jaeschke, Holger; Löf, Christoffer; Jännäri, Meeri; Ruohonen, Suvi T.; Undeutsch, Henriette; Khalil, Moosa; Kero, Andreina; Poutanen, Matti; Toppari, Jorma; Chen, Min; Weinstein, Lee S.; Paschke, Ralf; Kero, Jukka
• Is Part Of: FASEB journal. Volume 32:Issue 11(2018)
• Page Start: 6239
• Page End: 6251
• Publication Date: 2018-05-25
• Subjects: Gnas -- thyroglobulin-Cre -- Gsa -- G protein; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201800211R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: 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 Gs ‐ and Gq/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 Gs protein α subunit (Gαs) in adult mice [tamoxifen‐inducible Gs protein a subunit deficient (iTGαs KO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGas KO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGαs 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 iTGαs KO mice at an older age. These tumors developed from nonrecombined thyrocytes still expressing Gαs in the presence of highly elevated serum TSH. In summary, we report that partial thyrocyte‐specific Gαs deletion leads to hypothyroidism but also to tumor development in thyrocytes with remaining Gαs expression. Thus, these mice are a novel model to elucidate the patho physiological consequences of hypothyroidism and TSHR/G</cAMP‐mediated tumorigenesis.—Patyra, K., Jaeschke, H., Löf, C., Jännäri, M., Ruohonen, S. T., Undeutsch, H., Khalil, M., Kero, A., Poutanen, M., Toppari, J., Chen, M., Weinstein, L. S., Paschke, R., Kero, J. Partial thyrocyte‐specific Gas deficiency leads to rapid‐onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma‐like lesions in mice. FASEB J. 32, 6239–6251 (2018). www.fasebj.org