ECE2017 Oral Communications Thyroid Disease 1 (5 abstracts)
Inducible thyrocyte-specific Gs alpha-deficient mice as a novel model for hypothyroidism
Konrad Patyra 1 , Holger Jaeschke 1 , Henriette Undeutsch 1 , Christoffer Löf 1 , Suvi Ruohonen 1 , Meeri Jännäri 1 , Min Chen 2 , Lee S. Weinstein 2 , Ralf Paschke 3 , Jorma Toppari 1 & Jukka Kero 1
1Institute of Biomedicine, Turku, Finland; 2Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; 3Division of Endocrinology and Metabolism, Departments of Medicine and Oncology and Arnie Charbonneau Cancer Institute, Cummings School of Medicine, University of Calgary, Calgary, Canada.
The thyroid gland produces thyroid hormones, which are essential regulators of growth, development and metabolism of the body and is mainly regulated by the thyroid stimulating hormone (TSH)/TSH receptor (TSHR) interplay. The TSHR couples to all four G protein families in vitro but only for the Gs and Gq signaling cascade a role has been identified in vivo. To gain further insights into the complex signaling networks mediated by G proteins in the thyroid, we generated a thyrocyte-specific tamoxifen-inducible Gs deficient mouse line (iTGsKO). Mice were injected with tamoxifen at P28 and phenotypic characterization was carried out by performing thyroid function tests at different ages. iTGsKO mice showed hypothyroidism at P56, four weeks after induction with tamoxifen. Furthermore, a decrease in thyroid weight and an increased pituitary weight support the conclusion of hypothyroidism in these mice. Morphometric analysis of the thyroid histology of iTGsKO mice with an age of 6 months (P168) showed that the thyrocyte layers between adjacent follicles and the follicle areas were significantly reduced when compared with controls. Interestingly, despite of an identical thyroid hormone status we observed a clear sex difference. In iTGsKO males, the body weight was significantly decreased at P70 when compared with control males but no weight difference was seen in females over the investigated time period of 6 months (P168). The lower body weight in iTGsKO males was associated with reduced fat mass. In summary, we show that iTGsKO mice are a useful tool for understanding the role of G-protein signaling in the thyroid as well as investigating the metabolic consequences in hypothyroidism.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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