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ATRAZINE STIMULATES THE RELEASE OF ACTH AND ADRENAL STEROIDS IN MALE WISTAR RATS
Citation:
LAWS, S. C., J. M. FERRELL, D. S. BEST, A. R. BUCKALEW, A. E. MURR, AND R. L. COOPER. ATRAZINE STIMULATES THE RELEASE OF ACTH AND ADRENAL STEROIDS IN MALE WISTAR RATS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Previously, we reported that atrazine (ATR) alters steroidogenesis in male Wistar rats resulting in increased serum corticosterone (C), progesterone (P), androgens and estrogens. The observation of increased C following single or multiple doses of ATR (up to 21 days of dosing) suggested that this chlorotriazine herbicide may alter corticotrophin releasing factor (CRF) and/or adrenocorticortropic hormone (ACTH) release. This study evaluates ACTH, C, P and testosterone (T) following a single dose of ATR. Sixty-day-old rats were acclimated to dosing with vehicle (methylcellulose) for 7-days by gavage. On day 8, the rats were divided into groups of 10, given a single dose of ATR (0, 5, 50, 100, 200 mg/kg, gavage) at 0900 (12/12 light cycle, on @ 0700) and killed 5, 15, 30, 60 or 180 min later. A dose-dependent increase in plasma ACTH was observed 15 and 30 min after ATR. Maximal ACTH levels were observed at 15 min with 2.5, 4.9 and 9.6-fold increases in the 50, 100 and 200 mg/kg groups,respectively. Dose-dependent increases in serum C and P were observed at 15 and 30 min. in the 50, 100, and 200 mg/kg groups with the maximal responses (9 ? 12 fold increases) occurring at 30 min post-dosing. C and P remained elevated in the 200 mg/kg males through 180 and 60 min., respectively. Increased serum T was observed at 30 min in the 100 and 200 mg/kg groups, and at 60 min in the 50 -200 mg/kg groups. Thus, this study shows that the ATR-induced increase in steroidogenesis is the result of increased ACTH secretion that may be mediated through a direct effect on the pituitary or central nervous system CRF release. Additional studies are ongoing to identify the primary target site for these effects, and to determine the role that fluctuations in adrenal steroids may play in mediating ATR-related adverse effects on the reproductive system. This abstract does not necessarily reflect EPA policy.