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Development of an In Vivo Androgen Receptor Activity System Using Transgenic Xenopus laevisEPA 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) RFA Text | Recipients Lists
Research Category: Academic Fellowships , Biology/Life Sciences , Fellowship - Biochemistry, Molecular Biology, Cell Biology, Development Biology, and Genetics
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.
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.