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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
Aging Alters Phenotypic Traits of Thyroid Dysfunction in Male Mice With Divergent Effects on Complex Systems but
Kathrin Engels1, Helena Rakov1, Georg Sebastian Hönes1
1Department of Endocrinology, Diabetes, and Metabolism, University Hospital Essen, University Duisburg-Essen, Germany.
Abstract:
Clinical manifestation of hyperthyroidism and hypothyroidism vary with age, with an attenuated, oligosymptomatic presentation of thyroid dysfunction (TD) in older patients. We asked, whether in rodents TD phenotypes are influenced by age and whether this involves changes in systemic and/or organ thyroid hormone (TH) signaling. Chronic hyper- or hypothyroidism was induced in male mice at different life stages (5, 12, and 20 months). TH excess resulted in pronounced age-specific body weight changes (increase in youngest and decrease in old mice), neither explained by changes in food intake (similar increase at all ages), nor by thermogenic gene expression in brown adipose tissue (BAT) or TH serum concentrations. Relative increase in body temperature and activity were more pronounced in old compared to young hyperthyroid mice. An attenuated hypothyroid state was found in old mice for locomotor activity and in heart and BAT on functional (less bradycardia) and gene expression level (heart and BAT). In contrast, decrease in body weight was pronounced in old hypothyroid mice. Thus, age has divergent impact on features of TD in mice, whereby effects on highly complex systems, such as energy homeostasis are not proportional to serum TH state, in contrast to organ-specific responses in heart and BAT.
Insights
Age significantly alters thyroid dysfunction (TD) in mice. Older mice show distinct responses to hyperthyroidism and hypothyroidism, impacting body weight and energy homeostasis differently than younger mice.
Area of Science:
- Endocrinology
- Comparative Physiology
- Aging Research
Background:
- Thyroid dysfunction (TD) presents differently across age groups, often with milder symptoms in older individuals.
- Understanding age-related variations in TD is crucial for accurate diagnosis and treatment.
Purpose of the Study:
- To investigate how age influences the phenotypic expression of thyroid dysfunction in rodents.
- To determine if age-related changes in systemic and organ-specific thyroid hormone (TH) signaling underlie these altered TD phenotypes.
Main Methods:
- Induced chronic hyperthyroidism and hypothyroidism in male mice at three different life stages (5, 12, and 20 months).
- Monitored body weight, food intake, body temperature, activity levels, and gene expression in brown adipose tissue (BAT).
- Assessed functional and gene expression changes in the heart and BAT.
Main Results:
- Hyperthyroidism caused age-specific body weight changes (gain in young, loss in old mice), independent of food intake or TH serum levels.
- Older hyperthyroid mice exhibited more pronounced increases in body temperature and activity.
- Hypothyroidism was attenuated in older mice regarding locomotor activity and cardiac/BAT function and gene expression, yet body weight loss was more severe.
Conclusions:
- Age significantly impacts the manifestation of thyroid dysfunction in mice, affecting complex systems like energy homeostasis in non-proportional ways to serum TH levels.
- Organ-specific responses in the heart and brown adipose tissue show age-dependent alterations in thyroid hormone signaling.
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