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

Zhenhong Li, Kevin J. Kroll, Kathleen M. Jensen, Daniel L. Villeneuve, Gerald T. Ankley, Jayne V. Brian, María S. Sepúlveda, Edward F. Orlando, James M. Lazorchak, Mitchell Kostich, Brandon Armstrong, Nancy D. Denslow, Karen Watanabe-Sailor

Research output: Contribution to journalArticle

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Abstract

Background: Endocrine 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).Results: 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.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., 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.

Original languageEnglish (US)
Article number63
JournalBMC Systems Biology
Volume5
DOIs
StatePublished - May 5 2011

Fingerprint

Trenbolone Acetate
Estrogen
Cyprinidae
Fish
Computational Model
Estradiol
Fishes
Androgens
Vitellogenins
Markov Chains
Estrogens
Plasma
Experimental Data
Markov Chain Monte Carlo Simulation
Steroids
Reproduction
Testosterone
Markov processes
Hormones
Testosterone Congeners

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Applied Mathematics
  • Modeling and Simulation
  • Computer Science Applications

Cite this

A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone. / Li, Zhenhong; Kroll, Kevin J.; Jensen, Kathleen M.; Villeneuve, Daniel L.; Ankley, Gerald T.; Brian, Jayne V.; Sepúlveda, María S.; Orlando, Edward F.; Lazorchak, James M.; Kostich, Mitchell; Armstrong, Brandon; Denslow, Nancy D.; Watanabe-Sailor, Karen.

In: BMC Systems Biology, Vol. 5, 63, 05.05.2011.

Research output: Contribution to journalArticle

Li, Z, Kroll, KJ, Jensen, KM, Villeneuve, DL, Ankley, GT, Brian, JV, Sepúlveda, MS, Orlando, EF, Lazorchak, JM, Kostich, M, Armstrong, B, Denslow, ND & Watanabe-Sailor, K 2011, 'A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone', BMC Systems Biology, vol. 5, 63. https://doi.org/10.1186/1752-0509-5-63
Li, Zhenhong ; Kroll, Kevin J. ; Jensen, Kathleen M. ; Villeneuve, Daniel L. ; Ankley, Gerald T. ; Brian, Jayne V. ; Sepúlveda, María S. ; Orlando, Edward F. ; Lazorchak, James M. ; Kostich, Mitchell ; Armstrong, Brandon ; Denslow, Nancy D. ; Watanabe-Sailor, Karen. / A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone. In: BMC Systems Biology. 2011 ; Vol. 5.
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abstract = "Background: Endocrine 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).Results: 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.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., 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.",
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AU - Kroll, Kevin J.

AU - Jensen, Kathleen M.

AU - Villeneuve, Daniel L.

AU - Ankley, Gerald T.

AU - Brian, Jayne V.

AU - Sepúlveda, María S.

AU - Orlando, Edward F.

AU - Lazorchak, James M.

AU - Kostich, Mitchell

AU - Armstrong, Brandon

AU - Denslow, Nancy D.

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