Partial thyrocyte-specific Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.
| Title: | Partial thyrocyte-specific Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice. |
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| Authors: | Patyra K; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Turku Center for Disease Modeling, University of Turku, Turku, Finland.; Jaeschke H; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Löf C; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Turku Center for Disease Modeling, University of Turku, Turku, Finland.; Jännäri M; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Ruohonen ST; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Turku Center for Disease Modeling, University of Turku, Turku, Finland.; Undeutsch H; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Khalil M; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.; Kero A; Department of Pediatrics, Turku University Hospital, Finland.; Poutanen M; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Turku Center for Disease Modeling, University of Turku, Turku, Finland.; Toppari J; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Department of Pediatrics, Turku University Hospital, Finland.; Chen M; Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Weinstein LS; Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Paschke R; Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.; Kero J; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.; Turku Center for Disease Modeling, University of Turku, Turku, Finland.; Department of Pediatrics, Turku University Hospital, Finland. |
| Source: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2018 May 25, pp. fj201800211R. Date of Electronic Publication: 2018 May 25. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J |
| Imprint Name(s): | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley; Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| 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 α 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/Gs/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 Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice. |
| Contributed Indexing: | Keywords: G protein; Gnas; Gsα; thyroglobulin-Cre |
| Entry Date(s): | Date Created: 20180526 Latest Revision: 20240227 |
| Update Code: | 20260130 |
| DOI: | 10.1096/fj.201800211R |
| PMID: | 29799790 |
| Database: | MEDLINE |
Journal Article