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Adaptive Responses to Prochloraz Exposure in the Hypothalamic-Pituitary Gonadal Axis of Fathead Minnows
Citation:
BREEN, M., D. L. Villeneuve, G. T. Ankley, K. H. Watanabe, A. L. LLoyd, AND R. CONOLLY. Adaptive Responses to Prochloraz Exposure in the Hypothalamic-Pituitary Gonadal Axis of Fathead Minnows. Presented at Society of Toxicology 49th Annual meeting, Salti Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (DRTC) behaviors for endocrine effects ofthe fungicide prochloraz.
Description:
Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (DRTC) behaviors for endocrine effects ofthe fungicide prochloraz. The model includes several feedback regulatory loops within the HPG axis that mediate adaptive responses to endocrine stress. Fathead minnows were exposed to prochloraz at 30 or 300 ug/L for 8 days followed by an 8-day recovery phase. Adaptive changes in plasma estradiol levels occurred during exposure and treatment-related oscillations occurred post-exposure. Computer simulations were performed to compare the model-predicted DRTC with experimental data and to gain insight into how the feedback control mechanisms embedded in the HPG axis mediate these changes. As this work progresses we will obtain a refined understanding of how adaptive responses within the HPG axis of fathead minnows affect DRTC behaviors for prochloraz. This work was reviewed by the us. EPA and approvedjor publication but does not necessarily reflect Agency policy.