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ATRAZINE ALTERS STEROIDOGENESIS IN MALE WISTAR RATS
Citation:
Modic, W., J M. Ferrell, C R. Wood, J. W. LASKEY, R. L. COOPER, AND S. C. LAWS. ATRAZINE ALTERS STEROIDOGENESIS IN MALE WISTAR RATS. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
We have reported that atrazine (ATR, 200 mg/kg x 30 d) causes increased serum estrone (E) and estradiol (E2) in male wistar rats (Toxicol. Sci. 2000, 58:50-59). This study evaluates the short-term effects of ATR on E, E2 and their precursors in the steroidogenic pathway. Sixty-day-old male Wistar rats were gavaged once per day with ATR (0, 50 , 200 mg/kg) for 1, 4 or 21 days. Following the single dose, males were killed at 3, 6, or 24 hr. Males receiving multiple doses (4 or 21 days) were killed 3 hr following the last dose. Serum E, E2, testosterone (T), androstenedione (A), progesterone (P), and corticosterone (C) were measured. After one dose of ATR (200 mg/kg), P and C were increased at 3 hr. By 24 hr this dose elevated C and E. A and T were increased at 6 hrs for both doses. After 4 or 21 days of treatment with 200 mg/kg, C, E and E2 were elevated, but A and T remained at control levels. To determine the effect of ATR on adrenal steroidogenesis, ATR treated castrated males were examined. Despite reduced A and T levels in the castrated 200 mg/kg males, increased serum C, E, E2 mirrored previous results. Elevated P was also observed. No change in aromatase CYP19 mRNA was detected by real time RT-PCR in the testicular or hypothalamic tissues at any time point. These data suggest that elevated E and E2 were not strictly due to increased testicular steroidogenesis, altered aromatase mRNA, or substrate availability, but do not rule out a change in steroid metabolism or elimination. Although no CYP19 mRNA was detected in the adrenals, a stress-induced adrenal response may be partially responsible for the increase in steroids. However, in vitro data using a minced testes assay show an increase in T following a 4 hr exposure to ATR. Together, these data demonstrate that ATR can alter the steroidogenic pathway in male Wistar rats.