You are here:
Potiential role of the adrenal axis on the reproductive effects of Atrazine
Citation:
FRAITES, M. P., A. R. BUCKALEW, AND R. L. COOPER. Potiential role of the adrenal axis on the reproductive effects of Atrazine. Presented at 2009 Society of Toxicology Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
To present at SOT 2009 Annual meeting.
Description:
We and others reported that atrazine (ATR) disrupts the regulation of the ovulatory luteinizing hormone (LH) surge and the hormonal control of other reproductive functions in the rat. In addition, administration of ATR or the intermediate metabolite deisopropylatrazine (DIA) stimulate adrenocorticotropin (ACTH), corticosterone (CORT), and progesterone (P4). In contrast, the diaminochlorotriazine (DACT) metabolite minimally affects the hypothalamic-pituitary-adrenal axis (HPA). As adrenal activation may adversely affect LH secretion, these findings suggest that an atrazine-induced activation of the HPA axis may be an important part of the mode of action (MOA) through which the chlorotriazines alter reproductive function. Therefore, we hypothesized that only those metabolites that activate the HPA axis will affect LH release. Long-Evans rats displaying 4-day estrous cycles were restrained for 5 minutes or dosed by oral gavage at 0900h over one estrous cycle with vehicle (1% methyl cellulose), 75 mg/kg ATR, 10 or 60.2 mg/kg DIA, and 8.4 or 50.6 mg/kg DACT (14/10 light cycle, on at 0500h). Dosing began on the day of vaginal estrus. On the next vaginal proestrus, groups of rats were decapitated at 1600, 1800, and 2000h. Serum LH, prolactin (PRL), and P4 were measured by radioimmunoassay. Restraint, ATR, and both doses of DIA decreased the amplitude of the proestrous LH surge. In contrast, only the highest dose of DACT affected the surge. PRL was unchanged by any treatment. Unlike ATR, both doses of DIA decreased P4. Higher plasma levels achieved by direct dosing with DIA may have contributed to this. These results confirm that treatments which activate the HPA axis also alter LH release. These data suggest that activation of this axis contributes to the ATR- and DIA-induced disruption of LH secretion. Other MOAs must also be explored due the ability of DACT to alter LH without significant adrenal activation. Additional studies are planned using specific inhibitors of the HPA axis response to determine the role of this axis in the reproductive toxicity of ATR. This abstract does not necessarily reflect EPA policy.