FUNCTIONAL GENOMICS OF ENDOCRINE DISRUPTION

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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.