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A Computational Model of the Hypothalamic-pituitary-gonadal Axis in Male Fathead Minnows Exposed to 17 | *alpha* | -ethinylestradiol and 17 | *beta* | -estradiol
Citation:
WATANABE, K. H., Z. LI, K. KROLL, D. L. VILLENEUVE, N. GARCIA-REYERO, E. F. ORLANDO, M. S. SEPULVEDA, T. W. COLLETTE, D. R. EKMAN, G. T. ANKLEY, AND N. DENSLOW. A Computational Model of the Hypothalamic-pituitary-gonadal Axis in Male Fathead Minnows Exposed to 17 | *alpha* | -ethinylestradiol and 17 | *beta* | -estradiol. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 109(2):180-192, (2009).
Impact/Purpose:
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, 17-ethinylestradiol and 17ß-estradiol, 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 17-ethinylestradiol and 17ß-estradiol. Independent experimental datasets were used to evaluate model predictions. Although the model underpredicts the variance in some of the measured steroid hormone concentrations, we found good agreement between our model predictions and a variety of measured endpoints, and conclude that this model provides a reasonable representation of the HPG-axis in male FHM.
Description:
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, 17-ethinylestradiol and 17â-estradiol, 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 17-ethinylestradiol and 17â-estradiol. Independent experimental datasets were used to evaluate model predictions. Although the model underpredicts the variance in some of the measured steroid hormone concentrations, we found good agreement between our model predictions and a variety of measured endpoints, and conclude that this model provides a reasonable representation of the HPG-axis in male FHM.