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




Julkaisun tekijät: Konrad Patyra, Holger Jaeschke, Christoffer Löf, Meeri Jännäri, Suvi T. Ruohonen, Henriette Undeutsch, Moosa Khalil, Andreina Kero, Matti Poutanen, Jorma Toppari, Min Chen, Lee S. Weinstein, Ralf Paschke, Jukka Kero

Kustantaja: FEDERATION AMER SOC EXP BIOL

Julkaisuvuosi: 2018

Journal: FASEB Journal

Tietokannassa oleva lehden nimi: FASEB JOURNAL

Lehden akronyymi: FASEB J

Volyymi: 32

Julkaisunumero: 11

Sivujen määrä: 13

ISSN: 0892-6638

DOI: http://dx.doi.org/10.1096/fj.201800211R


Tiivistelmä
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 subunit (Gαs) in adult mice [tamoxifen-inducible G(s) protein subunit deficient (iTGαsKO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGαsKO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGαsKO mice. Unexpectedly, hyperplastic follicles and papillary thyroid cancer-like tumor lesions with increased proliferation and slightly increased phospho-ERK1/2 staining were found in iTGαsKO 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 pathophysiological consequences of hypothyroidism and TSHR/G(s)/cAMP-mediated tumorigenesis.Patyra, K., Jaeschke, H., Lof, C., Jannari, 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 Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.


Last updated on 2021-24-06 at 09:33