Dataset Information

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

ABSTRACT:

Background

Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17?-ethynylestradiol is a synthetic estrogen used in birth control pills. 17?-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17?-ethynylestradiol and 17?-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., 17?-ethynylestradiol) or androgens (i.e., 17?-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17?-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, 17?-ethynylestradiol-exposed, and 17?-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., 17?-ethynylestradiol) or androgens (e.g., 17?-trenbolone) affect plasma concentrations of 17?-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.

SUBMITTER: Li Z

PROVIDER: S-EPMC3118352 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Publications

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

Li Zhenhong Z Kroll Kevin J KJ Jensen Kathleen M KM Villeneuve Daniel L DL Ankley Gerald T GT Brian Jayne V JV Sepúlveda María S MS Orlando Edward F EF Lazorchak James M JM Kostich Mitchell M Armstrong Brandon B Denslow Nancy D ND Watanabe Karen H KH

BMC systems biology 20110505

<h4>Background</h4>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 physiol ...[more]

PMID: 21545743

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