Reproductive impacts of excreted and environmental estrogens, and natural steroid transfer between individuals

排泄物和环境雌激素的生殖影响以及个体之间的天然类固醇转移

• 批准号: 1199-2010
• 负责人: DeCatanzaro, Denys
• 金额: $ 3.06万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=473451
• 关键词: Reproductive; impacts; excreted; environmental; estrogens

Steroid hormones such as estrogens are normally understood to act only within the body that produces them. This lab has been collecting evidence that steroids can also pass between individuals, being excreted by one individual and then absorbed by others. We are studying this in lab mice; however this research should be relevant to many species because steroid dynamics are very similar across mammals. The urine of male mice contains high levels of estradiol, the most powerful estrogen. Males emit more estradiol when they are near females. This is associated with two well-known pheromonal effects: 1) advancement of the age of puberty in juvenile females, and 2) disruption of early pregnancy in females inseminated by another male. Both of these phenomena can be mimicked by giving females very small amounts of estrogens, which produce these effects by acting on receptors in the uterus and possibly also in the brain. We think that the estradiol in males' urine may simply be getting into females' bodies. In order to prove this, we are tracing radiolabelled (3H) estradiol from males' circulation through their urine into nearby females' circulation and to receptors in the uterus. We will also look at 3H-estradiol uptake in the hypothalamus of the brain, where estrogens control female sexual behaviour. Our work on the pheromonal effects of excreted estrogens needs to be reconciled with some older theories about the chemistry of mammalian pheromones. We will compare the impacts of estrogens with chemicals that have been suggested by other researchers. We will also investigate other sources of estrogens from outside the body, including phytoestrogens found in plant-based foods and manmade environmental contaminants such as bisphenol-A (BPA) from some plastics, as these can act on the same mechanisms as do excreted estrogens. We will study how these different sources of estrogens might interact to influence the age of female puberty and the outcome of early pregnancy. This research could transform understanding of the chemical nature of mammalian pheromones, while providing insights into the chemical factors that influence the age of female puberty and determine the success or failure of early pregnancy.

通常认为雌激素等类固醇激素仅在产生它们的体内起作用。该实验室一直在收集证据，证明类固醇也可以在个体之间传递，被一个人排泄，然后被其他人吸收。我们正在实验室小鼠身上研究这一点；然而，这项研究应该与许多物种相关，因为哺乳动物中的类固醇动力学非常相似。雄性小鼠的尿液含有高含量的雌二醇，这是最强的雌激素。当雄性靠近雌性时，会释放更多的雌二醇。这与两种众所周知的信息素效应有关：1）幼年雌性青春期提前，2）由另一名雄性授精的雌性早期妊娠受到破坏。这两种现象都可以通过给女性注射极少量的雌激素来模拟，雌激素通过作用于子宫中的受体（也可能是大脑中的受体）来产生这些效果。我们认为男性尿液中的雌二醇可能只是进入女性体内。为了证明这一点，我们正在追踪男性循环中的放射性标记 (3H) 雌二醇，通过尿液进入附近女性的循环和子宫中的受体。我们还将研究大脑下丘脑中 3H-雌二醇的摄取，雌激素控制女性性行为。我们对分泌雌激素的信息素影响的研究需要与一些关于哺乳动物信息素化学的旧理论相协调。我们将比较雌激素与其他研究人员建议的化学物质的影响。我们还将研究体外雌激素的其他来源，包括植物性食品中发现的植物雌激素和人造环境污染物，例如某些塑料中的双酚 A (BPA)，因为它们的作用机制与排出的雌激素相同。我们将研究这些不同来源的雌激素如何相互作用，从而影响女性青春期的年龄和早期妊娠的结果。这项研究可以改变对哺乳动物信息素化学性质的理解，同时提供对影响女性青春期年龄和决定早期妊娠成败的化学因素的见解。