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: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=513029
• 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只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，由一个个体排出，然后被另一个个体吸收。我们正在实验室老鼠身上进行研究；然而，这项研究应该与许多物种相关，因为类固醇动力学在哺乳动物中非常相似。雄性老鼠的尿液中含有高水平的雌二醇，这是最强大的雌激素。当雄性靠近雌性时，它们会释放出更多的雌二醇。这与两种众所周知的信息素效应有关：1)年轻雌性的青春期提前；2)被另一只雄性授精的雌性的早孕中断。这两种现象都可以通过给女性极少量的雌激素来模拟，这些雌激素通过作用于子宫和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了女性的体内。为了证明这一点，我们正在追踪放射性标记（3H）雌二醇从男性血液循环通过尿液进入附近女性血液循环并进入子宫内的受体。我们还将研究大脑下丘脑中3h -雌二醇的摄取，在那里雌激素控制着女性的性行为。我们对排泄的雌性激素的信息素效应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。我们将比较雌激素和其他研究人员提出的化学物质的影响。我们还将研究体外雌激素的其他来源，包括植物性食品中的植物雌激素和人造环境污染物，如一些塑料中的双酚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，影响女性青春期的年龄和早孕的结果。这项研究可以改变对哺乳动物信息素化学性质的理解，同时为影响女性青春期年龄和决定早孕成败的化学因素提供见解。