You are here:
EFFECTS OF ATRAZINE (ATR), DEISOPROPYLATRAZINE (DIA), AND DIAMINOCHLOROTRIAZINE (DACT) ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN FEMALE RATS
Citation:
FRAITES, M. P., S. C. LAWS, J. M. FERRELL, A. R. BUCKALEW, AND R. L. COOPER. EFFECTS OF ATRAZINE (ATR), DEISOPROPYLATRAZINE (DIA), AND DIAMINOCHLOROTRIAZINE (DACT) ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN FEMALE RATS. Presented at SOT Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
presentation
Description:
Previously we reported that a single dose of ATR herbicide stimulated HPA axis activation in the male rat while its primary metabolite, DACT, did so to a lesser extent. In this study, we evaluated the effects of ATR, DACT, and an intermediate metabolite, DIA, on adrenocorticotropin (ACTH), corticosterone (C) and progesterone (P) in the female rat. Females displaying 4-day estrous cycles were predosed by oral gavage with vehicle (1% methyl cellulose, MC) for 5 days after which they received 4 consecutive doses of vehicle, ATR (12.5 or 75 mg/kg/day), or equimolar doses of DACT or DIA beginning on the day of estrus at 0900 (14/10 light cycle, lights on at 0500). Another group of regularly cycling females was dosed once with MC, 75 mg/kg ATR, or an equimolar dose of DACT or DIA at 0900 on proestrus. All rats were decapitated 15 minutes after the last dose. Plasma ACTH and serum C and P were measured by radioimmunoassay. Four doses of 75 mg/kg/day ATR significantly elevated circulating ACTH, C, and P compared to MC-treated controls. Multiple doses of 12.5 mg/kg/day ATR significantly elevated C, but not ACTH or P. Circulating ACTH, C, and P rose after multiple high, but not low, doses of DIA while neither exposure to DACT had an effect. A single high dose of ATR or DIA significantly elevated all hormones examined. Levels of ACTH and P were markedly greater than those measured after 4 doses while C levels were comparable between dose groups. One high dose of DACT had no effect on hormone levels. We conclude that ATR and DIA activate HPA axis activity in the female rat while DACT has no effect 15 minutes after dosing. Observed differences in hormone responses between single and multiple doses may reflect augmented adrenal sensitivity or higher baseline C after a 4-dose exposure. Additional studies will identify the primary target site of these effects, and will determine the role of adrenal steroids in mediating ATR-induced adverse effects on the reproductive system.