Perinatal and chronic effects of flavonoids and polyphenolic compounds, contained in nutrition, on the thyroid hormone axis as well as endpoints and networks regulated by thyroid hormones

营养中所含的类黄酮和多酚化合物对甲状腺激素轴以及甲状腺激素调节的终点和网络的围产期和慢性影响

• 批准号: 5403296
• 负责人: Professor Dr. Josef Köhrle
• 金额: --
• 依托单位: Institut für Experimentelle Endokrinologie (CVK)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5403296?language=en
• 关键词: Perinatal; chronic; effects; flavonoids; polyphenolic

Phenolic secondary metabolites of plants, ubiquitous dietary constituents, influence feedback regulation of hormonal networks, such as the pituitary-thyroid-periphery axis. They disturb thyroid hormone action, especially under iodine deficiency, which still prevails in many parts of Europe. Apart from direct effects on the thyroid gland, flavonoids displace thyroid hormone from transthyretin, the most conserved transport protein for thyroid hormone and retinol (Vitamin A) and thus alter hormone bioavailability. We hypothesise that flavonoids interfere with further thyroid hormone binding sites especially during the peri- and postnatal period which is most sensitive to altered thyroid hormone state, especially under concomitant iodine deficiency. To identify novel targets of flavonoid and thus also thyroid hormone action (pregnant) transthyretin knockout mice will be (chronically) exposed to representative nutritional flavonoids and polyphenolic compounds. Using gene expression profiling techniques (DNA-arrays and DNA-chips) and molecular target analysis of (tissue-specific) thyroid hormone action our studies aim to identify new endpoints and readouts for flavonoid and thyroid hormone action especially during development. Experiments using established human thyroid cell lines will analyse mechanisms of flavonoid action on thyrocytes apart from binding competition to transthyretin. We expect novel information on i) potential flavonoid effects on the perinatal 'imprinting' and programming of the set points of endocrine feedback regulation of the thyroid axis, both for the exposed and the subsequent generation(s), ii) new endpoints of flavonoid action and their suitability as 'biomarkers' in animal and human thyrocyte models, and on iii) useful parameters for future safety and risk Initially apigenin, 8-prenylnaringenin, xanthohumol, malvidin-3-Glycoside, the synthetic F21388 and, as 'standard', genistein will be employed.

植物的酚类次生代谢物是普遍存在的膳食成分，影响激素网络的反馈调节，如垂体-甲状腺-外周轴。它们干扰甲状腺激素的作用，特别是在缺碘的情况下，这种情况在欧洲许多地区仍然普遍存在。除了对甲状腺的直接影响外，类黄酮还取代甲状腺素运载蛋白（甲状腺素运载蛋白是甲状腺激素和视黄醇（维生素A）最保守的转运蛋白）中的甲状腺激素，从而改变激素的生物利用度。我们假设，黄酮类化合物干扰进一步甲状腺激素结合位点，特别是在出生后和出生后期间，这是最敏感的甲状腺激素状态改变，特别是在伴随碘缺乏症。为了鉴定类黄酮的新靶点以及甲状腺激素作用的新靶点，将甲状腺素运载蛋白敲除小鼠（长期）暴露于代表性的营养类黄酮和多酚化合物。使用基因表达谱技术（DNA阵列和DNA芯片）和（组织特异性）甲状腺激素作用的分子靶点分析，我们的研究旨在确定黄酮和甲状腺激素作用的新终点和读数，特别是在发育过程中。使用已建立的人甲状腺细胞系的实验将分析类黄酮对甲状腺细胞的作用机制，除了与甲状腺素运载蛋白的结合竞争。我们期待新的信息i）潜在的黄酮类化合物对围产期的“印记”和甲状腺轴的内分泌反馈调节的设定点的编程的影响，对于暴露的和随后的几代人，ii）黄酮类化合物作用的新终点及其作为动物和人类甲状腺细胞模型中的“生物标志物”的适用性，以及iii）用于未来安全性和风险的有用参数。将使用8-异戊烯基柚皮素、黄腐酚、锦葵色素-3-糖苷、合成的F21388和作为“标准”的染料木黄酮。