Sex-specific phenotypes of hyperthyroidism and hypothyroidism in aged mice

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.Electronic supplementary materialThe online version of this article (10.1186/s13293-017-0159-1) contains supplementary material, which is available to authorized users.

Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine

“…A shortcoming of our study is that we only determined the age effect at two time points (basal and 12 hours after acute T 4 challenge), and that we cannot extrapolate on long-term effects on the organism. However, in previous studies we have observed age-dependent differences on phenotypic traits of chronic hyper-and hypothyroidism in mice and think that they are of physiological relevance (26,27). A strength of our study is the characterization of very old mice of 23 months of age in a direct comparison to 3 months old mice.…”

Partial thyrocyte‐specific Gα s deficiency leads to rapid‐onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma‐like lesions in mice

“…In contrast, no weight difference was seen in hypothyroid female iTGa s KO mice compared with controls despite a similar degree of hypothyroidism. Unlike in humans, where weight gain is a classic symptom of hypothyroidism, weight loss has been reported when hypothyroidism is induced pharmacologically in rodents (44,45). The reason for the different adaptation of body weight in hypothyroidism between male and female iTGa s KO mice remains unclear, but it may reflect, for example, sex-specific differences in tissue deiodinase activities, thyroid hormone uptake, and/or energy expenditure, as suggested previously (46).…”

Sex Impacts Cardiac Function and the Proteome Response to Thyroid Hormone in Aged Mice

“…One explanation is that the proteins we observed altered by TH status are predominantly involved in myocardial substrate utilization as opposed to structural or hypertrophic changes. Supporting this rationale, previous work in our lab showed TH treated aged male mouse heart experienced signi cant alterations in substrate utilization with fatty acids, but exhibited limited or unchanged cardiac functions compared to baseline or aged untreated [30,32,33]. Thus, we would need to do speci c studies on cardiac substrate utilization for fatty acids to de ne these sex-differences.…”

“…A prior investigation [30] reported that sex modulates TH action in both 12 and 20 months old C5/BL/7 mice. Those investigators studied effects of thyroid state on multiple systemic parameters such as body temperature and weight, as well as muscle strength and locomotor coordination.…”