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Development of an In Vivo Androgen Receptor Activity System Using Transgenic Xenopus laevis

EPA Grant Number: FP916443
Title: Development of an In Vivo Androgen Receptor Activity System Using Transgenic Xenopus laevis
Investigators: Roessig, Julie M.
Institution: University of California - Davis
EPA Project Officer: Manty, Dale
Project Period: January 1, 2004 through December 31, 2006
Project Amount: $105,344
RFA: STAR Graduate Fellowships (2004)
Research Category: Academic Fellowships , Fellowship - Biochemistry, Molecular Biology, Cell Biology, Development Biology, and Genetics , Biology/Life Sciences

Description:

Objective:

Over the last few decades, scientists have witnessed a significant decline in worldwide amphibian populations. Many factors have been suggested to contribute to this decline, including endocrine disruption (by endocrine disrupting compounds or EDCs). Many anthropogenic chemicals have the potential to interfere with an organism’s endocrine system, acting either as receptor agonists or antagonists, or by altering hormone metabolism. To determine the effects of EDCs, we must know an organism’s normal functioning state. Thyroid hormone (TH) is the inducer of amphibian metamorphosis, the process of converting a tadpole into a frog. Sex steroid hormones, such as androgens (testosterone, and dihydrotestosterone), drive the development of secondary sexual characteristics after metamorphosis is initiated. Important interactions between TH and androgens have been demonstrated in various vertebrates, although the precise mechanism is unknown. The objective of this research is to investigate the nature of the TH/androgen interaction.

Approach:

An in vivo androgen-responsive reporter system will be created using Xenopus laevis that will allow the investigation of the nature of this interaction. I plan to create transgenic animal models to serve as an in vivo detection system for androgen receptor activity. Two parallel systems will be employed: one utilizing an androgen response element based reporter gene, and a second approach utilizing a Gal4 DNA binding domain substituted AR and upstream activation sequence containing reporter genes. The system also should be useful for screening xenobiotics that interfere with both TH and androgen-dependent developmental processes at the molecular level.

Supplemental Keywords:

fellowship, endocrine disrupting compounds, EDCs, thyroid hormone, androgen receptor activity, amphibian declines, amphibian metamorphosis, androgens, Xenopus laevis, , Scientific Discipline, Health, RFA, Endocrine Disruptors - Environmental Exposure & Risk, Biology, endocrine disruptors, Biochemistry, Environmental Microbiology, Environmental Chemistry, Endocrine Disruptors - Human Health, aquatic ecosystem, endocrine disrupting chemicals, sexual development, EDCs, androgen responsive reporter system, in vivo screening system, reproductive processes, frog embryo study, estrogen response, sex differences

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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