Ecdysteroids in Postmenopausal Women– Health Effects and Metabolism

表皮甾体是一种极性多羟基甾体，也存在于各种植物中，如菠菜。菠菜中最丰富的表皮甾体是表皮酮。各种研究表明，蜕皮酮影响碳水化合物和脂肪代谢，并导致蛋白质生物合成的增加。自身的研究表明蜕皮酮与雌激素受体β的结合是激活这些代谢途径的相关机制。我们还在人类干预研究中检测到蜕皮酮的合成代谢和性能增强活性，并开发了血液和尿液的检测方法并研究其代谢。基于这些研究活动，世界反兴奋剂机构将蜕皮酮列为一种潜在的提高成绩的物质，并将其列入所谓的监测名单，以检测2020年体育运动中的滥用模式。同样，在绝经期和绝经后的女性中，肌肉质量和表现也起着至关重要的作用。雌激素血清浓度的降低与碳水化合物、蛋白质、骨骼和脂肪代谢活性的降低有关，从而增加患心血管疾病、肥胖、肌肉减少症、骨质疏松症和2型糖尿病的风险。本项目前三年的主要研究问题是：•蜕皮酮联合训练如何影响绝经后妇女的能量代谢、心血管和代谢风险、身体表现和身体成分？蜕皮酮代谢物和其他蜕皮类固醇的合成代谢效力是什么？蜕皮甾体和代谢物的分子机制是什么？绝经后妇女使用蜕皮酮是否会影响内源性类固醇的排泄？蜕皮酮是如何消除的，是否存在性别或年龄相关的差异？•年轻男性口服蜕皮酮后，在身体通道中，假设的14-脱氧是如何实现的？•富含蜕皮酮的饮食是否能够提供适量的蜕皮酮以支持训练效果？依给药来源，蜕皮酮的生物利用度是否有相关差异？•植物中潜在存在的代谢物和其他体外类固醇是否对德国人群饮食中的合成代谢活动有显著贡献？因此，在为期三个月的交叉设计四组双盲研究中，将对绝经后妇女补充ecdysterone与运动相结合的效果进行调查。此外，还将进行人体排泄研究和细胞培养实验。本研究可能为将皮质类固醇的营养摄取与训练相结合的概念的风险评估提供见解，该概念可能作为绝经后妇女心血管疾病、肌肉减少症、骨质疏松症或糖尿病发展的潜在预防策略。

Ecdysteroids are polar, polyhydroxy steroids that are also present in various plants such as spinach. The most abundant ecdysteroid in spinach is ecdysterone. A variety of studies showed that ecdysterone affects carbohydrate and fat metabolism and results in an increase in protein biosynthesis.Own investigations demonstrated binding of ecdysterone to the estrogen receptor beta as a relevant mechanism to activate these metabolic pathways. We also detected an anabolic and performance-enhancing activity of ecdysterone in a human intervention study and developed detection methods for blood and urine and study its metabolism. Based on these research activities the World Anti-Doping Agency has classified ecdysterone as a potential performance enhancing substance and included it on the so-called monitoring list to detect patterns of misuse in sports in 2020. Also in women during and after menopause, muscle mass and performance play a crucial role. The decrease in estrogen serum concentrations is associated with a decreased activity of carbohydrate, protein, bone, and fat metabolism resulting in an increased risk to develop cardiovascular diseases, obesity, sarcopenia, osteoporosis, and diabetes type 2. The main research questions addressed in the first three years of this project application are:•How does an administration of ecdysterone in combination with training affect energy metabolism, cardiovascular and metabolic risk, physical performance, and body composition in postmenopausal women?•What is the anabolic potency of ecdysterone metabolites and other ecdysteroids?•Which are the molecular mechanisms of ecdysteroids and metabolites? •Is the excretion profile of endogenous steroids influenced by an administration of ecdysterone in postmenopausal women?•How is ecdysterone eliminated and are there sex or age-related differences?•How is the hypothesized 14-desoxygenation, known from ecdysterone administration in young men, achieved during body passage following an oral administration of ecdysterone?•Is an ecdysterone-rich diet able to supply ecdysterone in suitable amounts to support training effects?•Is there a relevant difference in the bioavailability of ecdysterone dependent on the source of administration? •Do metabolite(s) and other ecdysteroids potentially present in plants significantly contribute to the anabolic activities of the diet of German population?Therefore, the effects of an ecdysterone supplementation in combination with exercise in postmenopausal women will be investigated in a four-arm double-blind study in a crossover design over a period of three months. Also, excretion studies in humans and cell culture experiments will be performed. This study may provide insights for risk assessment of the concept of combining nutritional uptake of ecdysteroids with training may serve as a potential prevention strategy for the development of cardiovascular disease, sarcopenia, osteoporosis, or diabetes in postmenopausal women.