FUNCTIONAL GENOMICS OF ENDOCRINE DISRUPTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究以花椒(Axolotl)为材料，建立了一种生态毒理基因组学模型。火蜥蜴基因组计划包括大约25,000个表达序列标签(EST)，用于定制设计包含4800个寡核苷酸引物的微阵列(即基因芯片)。该基因芯片被用来提供甲状腺激素(TH)介导的变态过程中的基因表达谱(GEP)，该变态是从三个不同发育阶段的紫杉醇提取的红细胞群体。两栖动物的变态和成熟是由内分泌系统通过下丘脑-垂体-甲状腺(HPT)轴来调节的。甲状腺分泌几种激素系统，包括三碘甲腺原氨酸和甲状腺素，统称为TH。其他激素，包括促性腺激素释放激素(GnRH)，也由HPT轴产生，影响发育至性成熟。由于许多环境污染物作为内分泌干扰物(EDs)，导致形态和生活史上的影响(如两性生殖、生长速度减慢、变态延迟)，因此有必要为正常的TH调节的变态和成熟建立一个标准。我们将遵循这一标准，并与Ed axolotl进行比较。我们还将改变生态背景(生长速度、竞争、温度)以及几种亚致死浓度的ED，阿特拉津。形态分析将与ED诱导的GEP变异进行比较。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An ecotoxicological genomics model was developed using salamander (axolotl). The salamander genome project includes approximately 25,000 expressed sequence tags (ESTs) that were used to custom design a microarray (i.e., gene chip) that included 4800 oligonucleotide primers. This gene chip was used to provide gene expression profiles (GEP) during thyroid hormone (TH) mediated metamorphosis is red-blood cell populations drawn from axolotl at three different developmental stages. Amphibian metamorphosis and maturation are regulated by the endocrine system via the hypothalamus-pituitary-thyroid (HPT) axis. The thyroid secretes several hormone systems, including triiodothyronine and thyroxine, referred to collectively as TH. Other hormones, including gonadotropin-releasing hormone (GNRH), are also produced by the HPT axis and influence development to sexual maturation. Because many environmental pollutants serve as endrocrine disruptors (EDs) that result in morphological and life historical effects (e.g., hermaphroditism, reduction in growth rate, delay in metamorphosis), it is essential to establish a standard for normal TH-regulated metamorphosis and maturation. We will follow this standard with comparison to ED axolotl. We will also vary ecological background (growth rate, competition, temperature) in conjunction with several sub-lethal concentrations of the ED, atrazine. Morphological assays will be compared with ED-induced variation in GEPs.