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THE EFFECTS OF ATRAZINE AND ITS METABOLITE DACT ON HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVATION IN ADULT MALE WISTAR RATS
Citation:
HOTCHKISS, M. G., J. M. FERRELL, A. E. MURR, R. L. COOPER, AND S. C. LAWS. THE EFFECTS OF ATRAZINE AND ITS METABOLITE DACT ON HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVATION IN ADULT MALE WISTAR RATS. Presented at Triangle Consortium for Reproductive Biology, Chapel Hill, NC, January 27, 2007.
Description:
Previous work in our laboratory has shown that a single administration of atrazine (ATR), a chloro-s-triazine herbicide that is used extensively throughout the USA and world, is able to induce a dose-dependent increase in plasma ACTH, with maximal concentrations observed at 15 min in the 50, 100 and 200 mg/kg dose groups. Dose-dependent increases in serum corticosterone (CORT) were also observed with maximal responses occurring at 30 min post-dosing. Administration of the ATR metabolite DACT (33.7 and 135 mg/kg) also increased ACTH, though this increase was not entirely dose responsive and was moderate when compared with the response to equimolar doses of ATR. The mechanism for this increase in hypothalamic-pituitary-adrenal axis (HPA-axis) activation observed after a single administration of these chemicals is unknown. To test whether administration of these chemicals by oral gavage alone could be causing HPA-axis activation through a generalized stress response, we conducted a conditioned taste aversion experiment using the same doses of ATR (5, 25, 50, 100, and 200mg/kg) and a single high dose of DACT (135mg/kg). Conditioned taste aversion is a classical conditioning paradigm that includes single trial learning of the association between consuming a novel food item and the development of illness or general malaise. This paradigm relies on activation of the HPA-axis for successful acquisition of the aversion and usually includes an all or nothing response that can last indefinitely. Results of our experiment showed a distinct dose-response relationship between ATR administration and the development of conditioned taste aversion, suggesting that the response is a graded one, more likely due to a direct effect of ATR on the HPA-axis than on an indirect effect through generalized stress or malaise. Finally, an in vitro pituitary perifusion experiment has been conducted to determine whether ATR has a direct agonistic effect on the pituitary gland, causing rapid release of ACTH into the bloodstream. Results from this experiment will also be reported. Given that there is considerable interaction between the hormonal regulation of the HPA and hypothalamic-pituitary-gonadal (HPG) axes in mammals, hormonal changes in the HPA-axis can greatly influence endocrine responses in the HPG-axis that can ultimately alter reproductive function. Thus, it is important to clearly understand the role that direct HPA-axis activation may have on reproductive function following exposure to environmental chemicals such as ATR and its metabolites.