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EVALUATION OF PITUITARY AND ADRENAL HORMONE RELEASE FOLLOWING EXPOSURE TO ATRAZINE AND ITS METABOLITE DEISOPROPYL-ATRAZINE (DIA), USING TISSUE PERIFUSION
Citation:
HOTCHKISS, M. G., S. C. LAWS, AND R. L. COOPER. EVALUATION OF PITUITARY AND ADRENAL HORMONE RELEASE FOLLOWING EXPOSURE TO ATRAZINE AND ITS METABOLITE DEISOPROPYL-ATRAZINE (DIA), USING TISSUE PERIFUSION. Presented at 2009 SOT Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This abstract represents a summary of data that will be presented at the SOT annual meeting. This work was conducted to elucidate the mechanisms underlying the endocrine effects and possible adverse outcomes associated with exposure to the chlorotriazine herbicide atrazine and its metabolites.
Description:
Atrazine (ATR) is one of the most widely used herbicides in the United States, with current total annual use of approximately 76 million pounds of active ingredient. Previous work in our laboratory has shown that ATR and its metabolite deisopropyl-atrazine (DIA) induce a dose-dependent increase in plasma ACTH, and serum corticosterone (CORT) and progesterone (P4), at 15 and 30 min after a single oral administration in vivo. Although the neuroendocrine mechanism for this increase in hypothalamic-pituitary-adrenal axis activation is currently unknown, ATR and DIA have been reported to directly alter steroidogenesis in vitro. To test whether ATR and DIA have a direct effect on the pituitary or adrenal glands, we examined hormone release from pituitary and adrenal tissue exposed to 50μM ATR or DIA, using a perifusion procedure. Tissues from adult male Wistar rats were exposed to two, twenty-minute challenges over a three hour period. A positive control challenge was included for pituitary (10nM CRF) and adrenal (1nM ACTH) tissues, as well as final challenge with KCl (60mM, pituitary), or ACTH (10nM, adrenal) to test for viability of the tissue at the completion of the perifusion. ATR and DIA had no apparent effect on release of ACTH or CORT. Interestingly, under these conditions, the parent compound (ATR) had no effect in either tissue, while treatment of adrenal tissue with its metabolite DIA produced a greater than two-fold increase from basal P4 release (3-7 pg/mg/min) during the 90 min following the onset of the first challenge. The DIA-induced increase in P4 release from the adrenal demonstrates a direct effect of the chemical on steroidogenesis in this tissue. These results suggest that increased adrenal hormone release observed in the male Wistar rat following in vivo exposure to these chlorotriazines is, in part, the result of a direct effect on the gland. This abstract does not necessarily reflect EPA policy.