title: A computational model of the hypothalamic: pituitary: gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone.
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.
authors.affiliation: Division of Environmental and Biomolecular Systems, Oregon Health & Science University, Beaverton, USA.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Li
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kroll
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Jensen
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
authors.forename: Jayne V
authors.initials: JV
authors.lastname: Brian
authors.forename: María S
authors.initials: MS
authors.lastname: Sepúlveda
authors.forename: Edward F
authors.initials: EF
authors.lastname: Orlando
authors.forename: James M
authors.initials: JM
authors.lastname: Lazorchak
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kostich
authors.forename: Brandon
authors.initials: B
authors.lastname: Armstrong
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Denslow
authors.forename: Karen H
authors.initials: KH
authors.lastname: Watanabe
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002138:Calibration; D003198:Computer Simulation; D003530:Cyprinidae; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008954:Models, Biological; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015203:Reproducibility of Results; D012098:Reproduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D014204:Trenbolone Acetate / Q000494:pharmacology*; D014819:Vitellogenins / Q000097:blood
chemical_list: D000728:Androgens; D004967:Estrogens; D014819:Vitellogenins; D013739:Testosterone; D004997:Ethinyl Estradiol; D004958:Estradiol; D014204:Trenbolone Acetate