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PREDICTIVE SIMULATION MODELING FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE
Citation:
Barton, H A., R W. Setzer, AND L. K. Potter. PREDICTIVE SIMULATION MODELING FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE. Presented at NIEHS Symp. on Biostatistical and Biomathematical Problems in Environmental Health, RTP, NC, June 7, 2002.
Description:
Predictive simulation modeling for antiandrogen impacts on rodent prostate
HA Barton1, RW Setzer1, LK Potter1,2
1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC
Changes in rodent prostate weight and function are very sensitive endpoints associated with adult and pubertal exposures to several classes of antiandrogens. We are extending a published model for the adult rat central axis (testosterone and luteinizing hormone pharmacokinetics and feedback regulation) to include the prostate and 5alpha-reductase conversion of testosterone to dihydrotestosterone. The goal is to predict how perturbations of the biological system create dose-response behaviors and evaluate assumptions of thresholds for the antiandrogenic impacts on prostate. The targets of antiandrogens include androgen receptor binding (e.g. vinclozolin or flutamide), testosterone synthesis (e.g. phthalates), and dihydrotestosterone synthesis (e.g. finasteride). Impacts on prostate being modeled include alterations in the expression of androgen receptor, 5alpha-reductase, and other genes that result in decreased fluid production, decreased cell proliferation, and increased apoptosis. The model will be a system of delayed differential algebraic equations and may be extended to describe pubertal animals. (This abstract does not represent EPA policy.)