Sex-specific selenoprotein expression and selenium metabolism

必需微量元素硒（Se）对维持健康和预防疾病很重要。硒水平低是癌症、心血管疾病和传染病的危险因素，还会损害免疫系统。硒代谢的性别差异可能影响某些疾病的易感性、发病机制和治疗效果。在主要硒转运蛋白硒蛋白P （SePP）基因失活的小鼠中，我们观察到性别特异性缺乏症状。肝源性SePP对硒代谢和体内平衡至关重要。有趣的是，SePP表现出性别二态表达模式。因此，我们的目的是分析硒代谢的性别特异性差异，并阐明为什么女性肝脏在某些硒蛋白的生物合成方面相对低效。以硒吸收、硒蛋白生物合成和硒代谢为重点，从硒的状态、形态和性别等方面进行比较。硒蛋白生物合成的两性二态途径将被表征，以考虑其对硒依赖健康效应的重要性，例如在实验诱发的抗炎反应中。这些数据将阐明硒代谢是否存在性别特异性途径，并可能表明雌性和雄性生物对硒的不同需求。

The essential trace element selenium (Se) is important for maintaining health and preventing disease. Poor Se status is a risk factor for cancer, cardiovascular and infectious diseases and compromises the immune system. Sex-specific differences in Se metabolism might impact on susceptibility, pathogenesis, and treatment efficiency of certain diseases. We observed sex-specific deficiency symptoms in mice upon genetic inactivation of the major Se transport protein, selenoprotein P (SePP). Liver-derived SePP turned out to be of central importance for Se metabolism and homeostasis. Interestingly, SePP displays a sexual dimorphic expression pattern. Therefore, we aim to analyse sex-specific differences of Se metabolism and elucidate why female liver is relatively inefficient in biosynthesis of certain selenoproteins. As main focus, Se uptake, selenoprotein biosynthesis and Se metabolism will be compared with respect to Se status, Se form and sex. Sexual dimorphic pathways for selenoprotein biosynthesis will be characterized in order to consider their importance for Se-dependent health effects, e.g. during an experimentally evoked antiinflammatory response. The data will clarify if there are sex-specific routes in Se metabolism and might indicate different needs of female and male organisms for this trace element.