Journal Article

A Computational Model of the Hypothalamic-Pituitary-Gonadal Axis in Male Fathead Minnows Exposed to 17α-Ethinylestradiol and 17β-Estradiol

Karen H. Watanabe, Zhenhong Li, Kevin J. Kroll, Daniel L. Villeneuve, Natàlia Garcia-Reyero, Edward F. Orlando, Maria S. Sepúlveda, Timothy W. Collette, Drew R. Ekman, Gerald T. Ankley and Nancy D. Denslow

in Toxicological Sciences

Volume 109, issue 2, pages 180-192
Published in print June 2009 | ISSN: 1096-6080
Published online April 2009 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfp069
A Computational Model of the Hypothalamic-Pituitary-Gonadal Axis in Male Fathead Minnows Exposed to 17α-Ethinylestradiol and 17β-Estradiol

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

Estrogenic chemicals in the aquatic environment have been shown to cause a variety of reproductive anomalies in fish including full sex reversal, intersex, and altered population sex ratios. Two estrogens found in the aquatic environment, 17α-ethinylestradiol (EE2) and 17β-estradiol (E2), have been measured in wastewater treatment effluents and have been shown to cause adverse effects in fish. To further our understanding of how estrogen exposure affects reproductive endpoints in the male fathead minnow (FHM, Pimephales promelas), a physiologically based computational model was developed of the hypothalamic-pituitary-gonadal (HPG) axis. Apical reproductive endpoints in the model include plasma steroid hormone and vitellogenin concentrations. Using Markov chain Monte Carlo simulation, the model was calibrated with data from unexposed FHM, and FHM exposed to EE2 and E2. Independent experimental data sets were used to evaluate model predictions. We found good agreement between our model predictions and a variety of measured reproductive endpoints, although the model underpredicts unexposed FHM reproductive endpoint variances, and overpredicts variances in estrogen-exposed FHM. We conclude that this model provides a robust representation of the HPG axis in male FHM.

Keywords: EE2; E2; fish; steroid hormones; environmental estrogen; Markov chain Monte Carlo simulation; predictive toxicology; system model

Journal Article.  8566 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.