Department of Biochemistry and Medical Chemistry, University of Pécs, Medical School, Pécs, Hungary.
Curr Med Chem. 2010;17(30):3542-74. doi: 10.2174/092986710792927813.
Herbivorous and omnivorous vertebrates have evolved in the presence of a variety of phytoestrogens, i.e., plant-derived compounds that can mimic, modulate or disrupt the actions of endogenous estrogens. Since the discovery of the estrus-inducing effects of some plant products in 1926, considerable effort has been devoted to the isolation and structural and pharmacological characterization of phytoestrogens. Recently, agricultural and industrial pollution has added anthropogenic estrogenic compounds to the list of environmental estrogens. Unlike phytoestrogens, these xenoestrogens tend to accumulate and persist in adipose tissue for decades and may cause long-lasting, adverse endocrine effects. Here we review the endocrine effects of known phytoestrogens and xenoestrogens with special emphasis on molecular structure-activity relationships. Phytoestrogens include flavonoids, isoflavonoids, chalcons, coumestans, stilbenes, lignans, ginsenosides and other saponins, as well as the recently discovered tetrahydrofurandiols. Fungal estrogenic compounds may enter the food chain via infested crops. Since some phytoestrogens have been shown to display organ-specific actions, pharmaceutical estrogen analogues with similar properties (selective estrogen receptor modulators, SERMs) are also discussed. Xenoestrogens include dichlorodiphenyltrichloroethane (DDT) and its metabolites, bisphenols, alkylphenols, dichlorophenols, methoxychlor, chlordecone, polychlorinated benzol derivatives (PCBs), and dioxins. While most of these compounds act through estrogen receptors alpha and beta, some of their effects may be mediated by other nuclear or membrane-bound receptors or receptor-independent mechanisms. Some might also interfere with the production and metabolism of ovarian estrogens. Better understanding of the molecular pharmacology of phyto- and xenoestrogens may result in the development of novel compounds with therapeutic utility and improved environmental protection.
草食性和杂食性脊椎动物在各种植物雌激素的存在下进化，即植物衍生的化合物，可以模拟、调节或破坏内源性雌激素的作用。自 1926 年发现某些植物产品具有诱导发情作用以来，人们已经投入了大量的精力来分离和结构和药理学表征植物雌激素。最近，农业和工业污染将人为雌激素化合物添加到环境雌激素清单中。与植物雌激素不同，这些外源性雌激素往往在脂肪组织中积累并持续数十年，可能会导致持久的、不利的内分泌影响。在这里，我们回顾了已知的植物雌激素和外源性雌激素的内分泌作用，特别强调了分子结构-活性关系。植物雌激素包括类黄酮、异黄酮、查耳酮、大豆素、苯乙烯、木脂素、人参皂苷和其他皂苷，以及最近发现的四氢呋喃二醇。真菌雌激素化合物可能通过受污染的作物进入食物链。由于一些植物雌激素已被证明具有器官特异性作用，因此也讨论了具有类似性质的药物雌激素类似物（选择性雌激素受体调节剂，SERM）。外源性雌激素包括滴滴涕（DDT）及其代谢物、双酚、烷基酚、二氯酚、甲氧氯、十氯酮、多氯联苯衍生物（PCBs）和二恶英。虽然这些化合物中的大多数通过雌激素受体 alpha 和 beta 起作用，但它们的一些作用可能通过其他核受体或膜结合受体或非受体依赖机制介导。一些化合物也可能干扰卵巢雌激素的产生和代谢。更好地了解植物雌激素和外源性雌激素的分子药理学可能会导致开发具有治疗用途和改善环境保护的新型化合物。
