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Bidirectional impact of atrazine-induced elevations in progesterone (P4) on the LH surge in the ovariectomized, estradiol (E2)-primed rat
Goldman, J., L. Davis, A. Murr, AND R. Cooper. Bidirectional impact of atrazine-induced elevations in progesterone (P4) on the LH surge in the ovariectomized, estradiol (E2)-primed rat. Presented at Society of Toxicology, March 11 - 14, 2013.
The present data show distinct and previously unreported differences in the effects of atrazine on the LH surge that are linked to stimulated adrenal steroid secretion and were dependent on the temporal relationship of the treatment to the surge. The results had been included in data previously made available for the scientific review of atrazine held during the late summer, 2011.
Multiple daily exposures to the herbicide atrazine (ATZ) have been reported to suppress the luteinizing hormone surge (LHS) in female rats. Exposure has also been found to elevate P4 concentrations, and an increase in P4 is known to have a different directional effect on LH depending on its temporal association to the surge. Consequently, the present study focused on the effects of ATZ dose and exposure duration on the LHS in OVX, E2-primed Long-Evans rats. ATZ was administered by gavage (1300h), and serial tail blood samples were taken at 1400, 1600, 1800 and 2000h following 1, 2 and 4 days of exposure. An initial study with 0 and 100 mg/kg (a dose previously demonstrated to suppress the surge after multiple treatments) significantly enhanced the afternoon LHS peak and area under the curve (AUC) in response to a 1-day exposure. In contrast, 4 daily treatments caused a significant suppression in both measures, whereas no effects were present following 2 days of dosing. After a 1-day treatment, prompt and marked elevations in serum P4 concentrations, attributable to adrenal secretion, were present at both 30 minutes and 1 hour, but by the 4th day a marked fall was present at 1 hour. A dose-response assessment was subsequently conducted with 0, 10, 30 and 100 mg/kg ATZ for 1 & 4 days. At 1 day, 100 mg/kg caused similar elevations in circulating P4, the LH peak and AUC, whereas 4 daily exposures resulted in a shift to a reduced AUC. No effects on the surge were observed with 10 or 30 mg/kg at 1 or 4 days. This influence on the LH surge indicates that the effectiveness of ATZ in inducing P4-associated bidirectional shifts in LH depends on both the dosage administered and importantly on the temporal association of exposure to the appearance of the surge. (This abstract does not represent EPA policy.)