Ecdysteroids in Postmenopausal Women– Health Effects and Metabolism

蜕皮类固醇对绝经后女性健康的影响和代谢

• 批准号: 512576039
• 负责人: Professor Dr. Patrick Diel
• 金额: --
• 依托单位: Institut für Pharmazie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/512576039?language=en
• 关键词: Ecdysteroids; Postmenopausal; Women; Health; Effects

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.

蜕皮类固醇是极性的多羟基类固醇，也存在于各种植物中，如菠菜。菠菜中最丰富的蜕皮甾类是蜕皮甾酮。大量研究表明，蜕皮甾酮影响碳水化合物和脂肪的代谢，导致蛋白质合成增加，自身的研究表明，蜕皮甾酮与雌激素受体β的结合是激活这些代谢途径的相关机制。我们还在人体干预研究中检测到蜕皮甾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，并研究了其代谢。根据这些研究活动，世界反兴奋剂机构已将蜕皮甾酮列为潜在的性能增强物质，并将其列入所谓的监测清单，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、骨和脂肪代谢的活性降低相关，导致发生心血管疾病、肥胖症、肌肉减少症、骨质疏松症和2型糖尿病的风险增加。该项目申请的前三年解决的主要研究问题是：·蜕皮甾酮与训练相结合的管理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？蜕皮甾酮代谢物和其他蜕皮甾体的合成代谢潜力是什么？·蜕皮激素及其代谢产物的分子机制是什么？·绝经后妇女服用蜕皮甾酮是否会影响内源性类固醇的排泄？蜕皮甾酮是如何消除的，是否存在性别或年龄相关的差异？·年轻男性服用蜕皮甾酮后，体内通道中如何实现假设的14-脱氧作用？·富含蜕皮甾酮的饮食是否能够提供适量的蜕皮甾酮以支持训练效果？·蜕皮甾酮的生物利用度是否存在依赖于给药来源的相关差异？·植物中可能存在的代谢物和其他蜕皮类固醇是否对德国人口饮食的合成代谢活动有显著贡献？因此，将在一项为期三个月的四臂双盲交叉研究中研究蜕皮甾酮补充剂联合运动对绝经后妇女的影响。 此外，还将进行人体排泄研究和细胞培养实验。这项研究可能提供的风险评估的概念相结合的营养摄取蜕皮类固醇与训练的见解，可能作为一个潜在的预防策略的发展，心血管疾病，肌肉减少症，骨质疏松症，或糖尿病在绝经后妇女。