A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone

Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total) converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well.The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol) or androgens (e.g., 17β-trenbolone) affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.In vertebrates, such as fish, the hypothalamic-pituitary-gonadal (HPG) axis controls reproductive processes through a variety of hormones which act on target tissues directly or indirectly [1,2]. The HPG axis can be altered by endocrine disrupting chemicals (EDCs) in the aquatic environment which mimic endogenous hormones, alter their concentrations, or block their actions [3].In recent years, many scientific studies have been conducted to study reproductive effects of EDCs in fathead minnow (FHM, Pimephales promelas), a model small fish species used in ecotoxicology [4-6]. Two EDCs, 17α-ethynylestradiol and 17β-trenbolone, have been widely studied as model estrogens and androgens, respectively [7-11]. Both compounds also are environmentally relevant contaminants.17α-ethynylestradiol (EE2), a synthetic estrogen used in birth control pills, enters the environment mainly through effluents from wastewater treatment facilities. The reported median EE2 concentration in the aquatic environment varies from <0.5 to 15 ng/L [12]. Due in part to its high binding affinity for estrogen receptor (ER) [13-15], EE2 affects the HPG ax