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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/5497

Title: A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17a-ethynylestradiol and 17b-trenbolone
Authors: Li, Z
Kroll, KJ
Jensen, KM
Villeneuve, DL
Ankley, GT
Brian, JV
Sepulveda, MS
Orlando, EF
Lazorchak, JM
Kostich, M
Armstrong, B
Denslow, ND
Watanabe, KH
Publication Date: 2011
Publisher: BioMed Central Ltd
Citation: BMC Systems Biology 5: 63, May 2011
Abstract: BACKGROUND: Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17a-ethynylestradiol is a synthetic estrogen used in birth control pills. 17b-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17a-ethynylestradiol and 17b-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas), a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17a-ethynylestradiol) or androgens (i.e., 17b-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17b-estradiol and testosterone) and vitellogenin (a precursor to egg yolk proteins). RESULTS: Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17aethynylestradiol- exposed, and 17b-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total) converged within 20,000 iterations. With the converged parameter values, we evaluated the model’s predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well. CONCLUSIONS: The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17a-ethynylestradiol) or androgens (e.g., 17b-trenbolone) affect plasma concentrations of 17b-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.
Description: Copyright @ 2011 Li et al.
Sponsorship: This research was supported in part by grants from the Medical Research Foundation of Oregon [Grant #0634 to K.W.]; U.S. Environmental Protection Agency (EPA) Science to Achieve Results (STAR) program [Cooperative Agreement # RD-83184801-0 to N.D., K.W., M.S., and E.O.]; and by resources from the National Center for Computational Toxicology of the EPA Office of Research and Development, awarded to the Ecological Exposure Research and Ecosystem Research Divisions (National Exposure Research Laboratory) in Cincinnati, OH and Athens, GA, respectively, and the Mid-Continent Ecology Division (National Health and Environmental Effects Research Laboratory) in Duluth, MN.
URI: http://www.biomedcentral.com/1752-0509/5/63
http://bura.brunel.ac.uk/handle/2438/5497
DOI: http://dx.doi.org/10.1186/1752-0509-5-63
ISSN: 1752-0509
Appears in Collections:Institute for the Environment Research Papers
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