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ALTERATION OF THE HYPOTHALAMIC-PITUITARY GONADAL (HPG) AXIS IN WISTAR MALE RATS FOLLOWING A PREPUBERTAL EXPOSURE TO THE CHLOROTRIAZINE HERBICIDE SIMAZINE
Citation:
STOKER, T. E., A. R. BUCKALEW, J. M. FERRELL, E. KAYDOS, AND R. L. COOPER. ALTERATION OF THE HYPOTHALAMIC-PITUITARY GONADAL (HPG) AXIS IN WISTAR MALE RATS FOLLOWING A PREPUBERTAL EXPOSURE TO THE CHLOROTRIAZINE HERBICIDE SIMAZINE . Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Chlorotriazine herbicides, such as atrazine and simazine (SIM), are used extensively in the U.S. each year and both parent compounds and metabolites are detected in ground water in areas of major usage. We found previously that atrazine suppresses serum luteinizing hormone and prolactin in the female rat by altering hypothalamic regulation. We have also demonstrated that puberty was delayed in the male and female rat when exposed to atrazine during the juvenile period. In addition, the chlorotriazine metabolites were equally potent in delaying puberty, which led to concern about cumulative effects of the metabolites and other parent compounds on pubertal development. For these reasons, we hypothesized that SIM, like atrazine, would delay pubertal progression in the male rat. In two separate experiments, males were administered SIM (0, 3.13,6.25, 12.5, 25, 50, 75, 100, 150 and 300 mg/kg) by oral gavage from postnatal day (PND)23 to 53. Males were monitored for preputial separation (PPS) and necropsied on PND 53. In both experiments, puberty was significantly advanced at 25 mg/kg. Consistent with the lower dose advancement of PPS, there was a non-monotonic dose response, with an elevation in LH, testosterone and androstenedione at the lower doses (6.25 to 75 mg/kg). There was a corresponding delay in PPS at 300 mg/kg and a decrease in seminal vesicle and prostate weights at the highest doses (150 to 300 mg/kg), with LH concentrations returning to normal. In conclusion, SIM appears to have a bimodal effect on puberty, with an increase in androgens and corresponding advancement in puberty at the lower doses and a delay in reproductive tract development in the higher doses. The fact that the two lower doses of SIM increased serum androgens and LH on PND53 and advanced PPS in the developing male would indicate that SIM activates the HPG axis. Further studies are planned to elucidate this activation and the specific mechanisms of these effects on male development. This abstract does not necessarily reflect EPA policy.