Estrogen receptor activity in zebrafish mating behaviors

斑马鱼交配行为中的雌激素受体活性

基本信息

批准号：
8130941
负责人：
Daniel Gorelick
金额：
$ 5.87万
依托单位：
CARNEGIE INSTITUTION OF WASHINGTON, D.C.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8130941
关键词：
Adult Affect Animals Behavior Biological Assay Brain Cell Count Cell Nucleus Cells Defect Development Dominant-Negative Mutation Doxycycline Embryo Environmental Pollution Estradiol Estrogen Receptors Estrogens Female Fishes Fluorescence Future Gene Expression Genetic Techniques Germ Cells Goals Gonadal Hormones Gonadal Steroid Hormones Gonadal structure Green Fluorescent Proteins Growth Hormones Human Hypothalamic structure In Vitro Label Lead Life Malignant Neoplasms Mammals Medial Mediating Methods Modeling Neurons Partner in relationship Pesticides Physiology Play Preoptic Areas RNA Splicing Rattus Receptor Activation Receptor Gene Reporter Role Site Staging Testing Tissues Transgenic Organisms Variant Vertebrates Zebrafish combat critical period dimorphism environment related cancer in vivo insight male neuronal circuitry neuronal growth protein expression receptor reproductive response sex small molecule steroid hormone tool

项目摘要

DESCRIPTION (provided by candidate): Differences between the brains of males and females contribute to their distinct physiology and behavior. Prominent sex-specific differences in cell number and connectivity are found in the hypothalamic nuclei of many vertebrates. These dimorphisms are mediated by sex hormones. In rats, for example, sex hormones secreted by the gonad during a critical period of development determine the size of the "sexually dimorphic nucleus" in the medial preoptic area of the hypothalamus, which contains more cells in males than in females. However, steroid hormones synthesized directly in the brain may also play a role in its sexual differentiation. The zebrafish provides a unique opportunity to visualize estrogen receptor activity directly in a live, developing vertebrate brain. Genetic techniques can also be used to produce adults that completely lack gonadal tissue. The overall goal of my project is to capitalize on transgenic zebrafish I have already developed to characterize estrogen-sensitive neurons in the preoptic area and hypothalamus and compare their organization in males and females. I will also explore the role gonadal hormones play in their development and in the activation of sexually dimorphic mating behaviors. The specific aims of this proposal are: 1) to assess whether the number and projections of estrogen sensitive neurons in the preoptic area differ between male and female zebrafish; 2) to determine whether inhibiting gonad differentiation and survival alters the organization of estrogen sensitive neurons in the preoptic area and the activation of mating behaviors; 3) to generate transgenic zebrafish that conditionally express a dominant negative estrogen receptor. This proposal seeks to understand how estrogen hormones affect the growth and connection of cells in the brain. Abnormal estrogen activity has been implicated in the growth of certain cancers, while many environmental contaminants (such as pesticides) disrupt normal estrogen activity, which can lead to reproductive defects or cancer. Gaining a better understanding of how estrogens function in the brain may provide insights that will allow us to better combat toxic environmental contaminants and cancer.

描述（由候选人提供）：男性和女性大脑的差异导致了他们独特的生理和行为。在许多脊椎动物的下丘脑核中发现了细胞数量和连接性的显着性别特异性差异。这些二态性是由性激素介导的。例如，在大鼠中，性腺在发育关键时期分泌的性激素决定了下丘脑内侧视前区“性二形核”的大小，雄性比雌性含有更多的细胞。然而，直接在大脑中合成的类固醇激素也可能在其性别分化中发挥作用。斑马鱼提供了一个独特的机会，可以直接在活的、发育中的脊椎动物大脑中观察雌激素受体的活动。遗传技术还可用于培育完全缺乏性腺组织的成年人。我的项目的总体目标是利用我已经开发的转基因斑马鱼来表征视前区和下丘脑的雌激素敏感神经元，并比较它们在雄性和雌性中的组织。我还将探讨性腺激素在其发育和性二态性交配行为激活中所发挥的作用。该提案的具体目的是：1）评估雄性和雌性斑马鱼视前区雌激素敏感神经元的数量和投射是否不同； 2) 确定抑制性腺分化和存活是否会改变视前区雌激素敏感神经元的组织和交配行为的激活； 3) 产生条件性表达显性负性雌激素受体的转基因斑马鱼。该提案旨在了解雌激素如何影响大脑细胞的生长和连接。异常的雌激素活性与某些癌症的生长有关，而许多环境污染物（例如农药）会破坏正常的雌激素活性，从而导致生殖缺陷或癌症。更好地了解雌激素在大脑中的作用可能会提供见解，使我们能够更好地对抗有毒环境污染物和癌症。