Syngenta Crop Protection LLC, Greensboro, North Carolina.
Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona.
Birth Defects Res. 2018 Feb 15;110(3):246-258. doi: 10.1002/bdr2.1130. Epub 2017 Nov 14.
Atrazine suppression of the LH surge slowly develops over time and peaks after 4 days; sensitivity to atrazine decreases after 8 or 14 days of dosing. Adaptation of the LH response was correlated with increased phase I and phase II liver enzyme activity/expression.
The effect of atrazine on the LH surge was evaluated in female Sprague-Dawley rats administered 100 mg/kg/day atrazine by gavage for 1, 2, 3, or 4 consecutive days or 6.5, 50, or 100 mg/kg/day atrazine for 4, 8, or 14 days.
No statistically significant effects of atrazine were seen on peak plasma LH or LH area under the curve (AUC) after one, two, or three doses of 100 mg/kg/day. Four daily doses of 50 or 100 mg/kg atrazine significantly reduced peak LH and LH AUCs, whereas 6.5 mg/kg/day had no effect. After 8 or 14 days of treatment, statistically significantly reduced peak LH and LH AUC were observed in the 100 mg/kg/day dose group, but not in the 6.5 or 50 mg/kg/day dose groups, although significantly reduced LH was observed in one sample 9 hr after lights-on in the 50 mg/kg/day dose group on day 14. The number of days of treatment required to achieve a significant suppression of the LH surge is consistent with the repeat-dose pharmacokinetics of the chlorotriazines.
The apparent adaptation to the effect of atrazine on the LH surge after 8 or 14 days may be related to the induction of phase I or, more likely, phase II metabolism observed in this study after 8 days, or to a decreased sensitivity of the hypothalamic-pituitary-adrenal axis or an homeostatic adaption of the effect of atrazine on the LH surge mechanism. Birth Defects Research 110:246-258, 2018. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.
莠去津对 LH 峰的抑制作用会随着时间的推移而缓慢发展，在 4 天后达到峰值；在给药 8 或 14 天后，对莠去津的敏感性会降低。LH 反应的适应性与Ⅰ相和Ⅱ相肝酶活性/表达的增加有关。
通过灌胃给予雌性 Sprague-Dawley 大鼠 100mg/kg/天莠去津，连续 1、2、3 或 4 天，或 6.5、50 或 100mg/kg/天莠去津，连续 4、8 或 14 天，评估莠去津对 LH 峰的影响。
单次、两次或三次给予 100mg/kg/天莠去津后，血浆 LH 峰值或 LH 曲线下面积（AUC）无统计学意义。连续 4 天给予 50 或 100mg/kg/天莠去津可显著降低 LH 峰值和 LH AUC，而 6.5mg/kg/天则无影响。8 或 14 天后，100mg/kg/天剂量组的 LH 峰值和 LH AUC 明显降低，但 6.5 或 50mg/kg/天剂量组无明显降低，尽管在第 14 天第 1 次光照后 9 小时，50mg/kg/天剂量组的一个样本中观察到 LH 明显降低。达到显著抑制 LH 峰所需的治疗天数与氯三嗪的重复剂量药代动力学一致。
8 或 14 天后对莠去津对 LH 峰抑制作用的明显适应可能与本研究中 8 天后观察到的Ⅰ相或更可能是Ⅱ相代谢诱导有关，也可能与下丘脑-垂体-肾上腺轴的敏感性降低或对 LH 峰机制的莠去津作用的体内平衡适应有关。出生缺陷研究 110:246-258,2018。©2017 作者。出生缺陷研究由 Wiley Periodicals, Inc. 出版。
