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Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###
Citation:
Riffle, B., S. Laws, AND R. Cooper. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###. Presented at Triangle Consortium for Reproductive Biology, March 01 - 02, 2013.
Impact/Purpose:
This abstract will be presented at the Triangle Consortium for Reproductive Biology, March 1-2, 2013, Duke University, Durham, NC
Description:
While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone (P4) over a 21- day exposure to the chiorotriazine herbicide, ATR. Adult Wistar male rats were dosed by oral gavage with 0, 5, 25, 75, or 200 mg/kg/d given either as a single dose or multiple daily doses (7, 14, or 21 doses) at 0900 hrs (nadir of circadian CORT rhythm) and were decapitated 30 minutes after the last dose (n10/group). Necropsy body weight was significantly lower than controls (p < 0.05) only in the 200 mg/kg group dosed for 21 days. Adrenal weights were unaffected by ATR at any time point. Serum CORT was elevated in response to a single dose of ATR (LOEL=5mg/kg). Serum CORT was also increased following 7 (LOEL=75mg/kg), 14 (LOEL=25mg/kg), and 21 (LOEL=75mg/kg) daily doses. A similar profile was observed for serum P4 following a single dose (LOEL=25 mg/kg), or 7 (L0EL75 mg/kg), 14 (LOEL75 mg/kg), and 21 (LOEL=200 mg/kg) doses of ATR. Urinary CORT (ratio of CORT/urinary creatinine), measured over a 6 hr period after dosing, was significantly increased in the ATR groups (e.g., LOEL for one dose =75 mg/kg, LOEL for 21 doses =75 mg/kg). These data demonstrate a HPA response after daily doses of ATR (e.g., 75 and 200 mg/kg) for up to 21 days. Further work is needed to evaluate the effects of ATR on the circadian CORT rhythm and to discern any impact on reproductive function. This abstract does not reflect US. EPA policy.