Sex-specific phenotypes of hyperthyroidism and hypothyroidism in aged mice |
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Authors: | Helena Rakov Kathrin Engels Georg Sebastian Hönes Klaudia Brix Josef Köhrle Lars Christian Moeller Denise Zwanziger Dagmar Führer |
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Institution: | 1.Department of Endocrinology, Diabetology and Metabolism,University Hospital Essen, University Duisburg-Essen,Essen,Germany;2.Department of Life Sciences and Chemistry,Jacobs University Bremen,Bremen,Germany;3.Charité-Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin,,Humboldt-Universit?t zu Berlin, and Berlin Institute of Health, Institut für Experimentelle Endokrinologie,Berlin,Germany;4.Department of Endocrinology, Diabetology and Metabolism, Clinical Chemistry – Division of Laboratory Research,University Hospital Essen, University Duisburg-Essen,Essen,Germany |
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Abstract: | BackgroundSex and age play a role in the prevalence of thyroid dysfunction (TD), but their interrelationship for manifestation of hyper- and hypothyroidism is still not well understood. Using a murine model, we asked whether sex impacts the phenotypes of hyper- and hypothyroidism at two life stages.MethodsHyper- and hypothyroidism were induced by i.p. T4 or MMI/ClO4-/LoI treatment over 7 weeks in 12- and 20-months-old female and male C57BL/6N mice. Control animals underwent PBS treatment (n?=?7–11 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination and strength) and serum thyroid hormone (TH) status.ResultsDistinct sex impact was found in eu- and hyperthyroid mice, while phenotypic traits of hypothyroidism were similar in male and female mice. No sex difference was found in TH status of euthyroid mice; however, T4 treatment resulted in twofold higher TT4, FT4 and FT3 serum concentrations in adult and old females compared to male animals. Hyperthyroid females consistently showed higher locomotor activity and better coordination but more impairment of muscle function by TH excess at adult age. Importantly and in contrast to male mice, adult and old hyperthyroid female mice showed increased body weight. Higher body temperature in female mice was confirmed in all age groups. No sex impact was found on heart rate irrespective of TH status in adult and old mice.ConclusionsBy comparison of male and female mice with TD at two life stages, we found that sex modulates TH action in an organ- and function-specific manner. Sex differences were more pronounced under hyperthyroid conditions. Importantly, sex-specific differences in features of TD in adult and old mice were not conclusively explained by serum TH status in mice. |
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