A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone

dc.contributor.authorLi, Zhenhong
dc.contributor.authorKroll, Kevin J
dc.contributor.authorJensen, Kathleen M
dc.contributor.authorVilleneuve, Daniel L
dc.contributor.authorAnkley, Gerald T
dc.contributor.authorBrian, Jayne V
dc.contributor.authorSepúlveda, María S
dc.contributor.authorOrlando, Edward F
dc.contributor.authorLazorchak, James M
dc.contributor.authorKostich, Mitchell
dc.contributor.authorArmstrong, Brandon
dc.contributor.authorDenslow, Nancy D
dc.contributor.authorWatanabe, Karen H
dc.date.accessioned2021-11-09T14:56:33Z
dc.date.available2021-11-09T14:56:33Z
dc.date.issued2011-05-05
dc.description.abstractEndocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17β-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17β-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., 17α-ethynylestradiol) or androgens (i.e., 17β-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17β-estradiol and testosterone) and vitellogenin (a precursor to egg yolk proteins). Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-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. 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., 17α-ethynylestradiol) or androgens (e.g., 17β-trenbolone) affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.en_US
dc.description.urihttps://doi.org/10.1186/1752-0509-5-63
dc.identifierhttps://doi.org/10.13016/zyxd-pbgn
dc.identifier.citationLi, Z., Kroll, K.J., Jensen, K.M. et al. A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone. BMC Syst Biol 5, 63 (2011).en_US
dc.identifier.urihttp://hdl.handle.net/1903/28095
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isAvailableAtCollege of Agriculture & Natural Resourcesen_us
dc.relation.isAvailableAtAnimal & Avian Sciencesen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectAndrogen Receptoren_US
dc.subjectLuteinizing Hormoneen_US
dc.subjectMarkov Chain Monte Carlo Simulationen_US
dc.subjectCalibrate Model Parameteren_US
dc.subjectReproductive Endpointen_US
dc.titleA computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenboloneen_US
dc.typeArticleen_US

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