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Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz
Citation:
BREEN, M., D. L. VILLENEUVE, G. T. ANKLEY, K. H. WATANABE, M. BREEN, A. L. LLOYD, AND R. B. CONOLLY. Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz. Presented at 49th annual meeting of SOT, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and altered dose response and time-course (DRTC) behaviors to minimize the effects caused by stressors. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict DRTC for endocrine disrupting fungicide prochloraz. The model includes several feedback regulatory loops to analyze the adaptive response to endocrine stress from exposures to the fungicide prochloraz. Experiments were performed using adult fathead minnows with an 8-day exposure and 8-day recovery phase, and multiple samples were collected during both phases. Computer simulations were performed to compare the model-predicted DRTC with experimental data. This model characterizes the mechanisms underlying the adaptive response to refine DRTC behavior for prochloraz, and helps us better understand whether exposures pose health risks.
Description:
There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and altered dose response and time-course (DRTC) behaviors to minimize the effects caused by stressors. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict DRTC for endocrine disrupting fungicide prochloraz. The model includes several feedback regulatory loops to analyze the adaptive response to endocrine stress from exposures to the fungicide prochloraz. Experiments were performed using adult fathead minnows with an 8-day exposure and 8-day recovery phase, and multiple samples were collected during both phases. Computer simulations were performed to compare the model-predicted DRTC with experimental data. This model characterizes the mechanisms underlying the adaptive response to refine DRTC behavior for prochloraz, and helps us better understand whether exposures pose health risks.