EAPSI: Membrane Steroid Hormone Receptor Activity of Fathead Minnow when Exposed to a Contaminants of Emerging Concern Mixture

在水生生态系统中，鱼类一生都暴露在复杂的化学混合物中。其中一些化学物质模仿生物体中的激素。这些类似激素的化学物质可能反过来改变鱼类的行为，从降低雄性保卫巢穴的活力到幼鱼的游泳表现。在化学物质暴露的严重情况下，整个鱼类种群可能会崩溃。这种新出现的化学品混合物（CECs）是水生生态系统中激素样化合物的常见来源。在过去几年中，CEC的使用随着人口的增长而增加。虽然单一的CECs对鱼类的影响已经被探索过，但整个CECs混合物的影响还没有。这项获奖研究将通过克隆和表征膜类固醇激素受体，包括雌激素受体，来阐明化学物质在复杂混合物中所采取的途径，以确定分子差异是否与行为终点的变化有关。这项研究将与日本札幌北海道大学的内分泌干扰和雌激素样化学物质对发育的影响方面的知名专家吉野胜博士合作进行。已经发现CECs会影响繁殖力、觅食能力和其他顶端端点。本项目将重点研究环境来源的城市CEC混合物对promelas膜受体（即GPR30和膜孕酮受体）的激活。大多数膜类固醇激素受体是G蛋白偶联受体，因此将进行第二信使分析以了解膜类固醇受体的机制，并确定其是否与cec暴露和/或行为终点有关。本项目的目的是：(1)克隆和鉴定promelas膜类固醇激素受体；(2)研究cecc暴露下膜受体活性与行为终点的相互作用。该项目将支持一个更大的项目，旨在描述和评估来自城市来源的环境来源的CECs混合物如何影响劳伦森大湖盆地的黑头鲦鱼种群。该奖项由美国国家科学基金会和日本科学促进会共同资助，隶属于东亚和太平洋暑期研究所项目，支持一名美国研究生进行暑期研究。

In the aquatic ecosystem, fish are exposed throughout life to complex mixtures of chemicals. Some of these chemicals mimic hormones in organisms. These hormone-like chemicals may in turn alter fish behavior, from decreased the vigor of male nest defense to swimming performance in larval fathead minnows (Pimephales promelas). In severe cases of chemical exposure, the entire fish population can collapse. This mixture of chemicals of emerging concern (CECs), are a common source of hormone-like compounds in aquatic ecosystems. Over the past few years, CEC use has increased alongside the growth in human population. Though the effects of single CECs have been explored in fishes, the effects of an entire mixture of CECs has not. The award research will shed light on the pathway chemicals take when present in a complex mixture by cloning and characterizing membrane steroid hormone receptors, including the estrogen receptors, to determine if a molecular difference is related to changes in behavioral endpoints. This research will be conducted in collaboration with Dr. Yoshinao Katsu, a noted expert in endocrine disruption and developmental effects of estrogen-like chemicals, at Hokkaido University in Sapporo, Japan. CECs have been found to affect fecundity, foraging ability, and other apical endpoints. This project will focus on the membrane receptors (i.e. GPR30 and membrane progesterone receptor) activation by an environmentally derived urban CEC mixture in P. promelas. Most membrane steroid hormone receptors are G protein-coupled receptors, thus a second messenger analysis will be conducted to understand the membrane steroid receptors mechanisms and determine if it is linked to CEC-exposure and/or behavioral endpoints. The objectives of this projects are: (1) To clone and characterize membrane steroid hormone receptors in P. promelas; (2) To examine the interaction of the membrane receptor activity with behavioral endpoints under CEC-exposure. This project will support a larger project seeking to characterize and evaluate how environmentally derived CECs mixture from urban sources affect fathead minnow populations in the Laurentian Great Lake Basin. This award, under the East Asia and Pacific Summer Institutes program, supports summer research by a U.S. graduate student and is jointly funded by NSF and the Japan Society for the Promotion of Science.