Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice. Aged (18–20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting. Serial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference and p < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways. We identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction.

中文翻译：

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性别影响老年小鼠的心脏功能和蛋白质组对甲状腺激素的反应

性别和年龄对甲状腺功能有重要影响。性别会影响甲状腺疾病（TDs）的风险和临床表达，随着年龄的增长，可能会引发TDs的发展。心脏功能受甲状腺激素水平和性别差异的影响。因此，我们调查了老年小鼠甲状腺功能异常的基于性别的心脏反应中涉及的蛋白质组学变化。年龄（18–20个月）的雄性和雌性C57BL / 6小鼠被喂食以产生正常的甲状腺，甲状腺功能减退或甲状腺功能亢进状态。进行连续超声心动图检查以评估心脏功能。通过2-D DIGE和LC-MS / MS评估心脏蛋白质谱中的蛋白质组学变化，并通过免疫印迹确认其子集。连续超声心动图检查显示，无论治疗如何，心室功能均保持不变。与性别无关，心率和大小增加（甲状腺功能亢进）或减少（甲状腺功能减退）。六组之间的成对比较确定了55种蛋白质（差异≥1.5倍，p <0.1）。与同性对照相比，雌性甲状腺功能减退心脏中有26/55蛋白的变化，而男性甲状腺功能减退以及雄性和雌性甲状腺功能亢进的心脏中有15/55的蛋白变化。这些蛋白质定位于氧化磷酸化，组织重塑和炎症反应途径。我们鉴定了预测的和新型的蛋白，这些蛋白具有响应甲状腺激素状态的性别特异性差异表达，提供了与甲状腺功能障碍相关的蛋白目录。