Endocrine Toxicology Branch, MD72, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Reproduction. 2013 Aug 12;146(4):305-14. doi: 10.1530/REP-13-0011. Print 2013 Oct.
Multiple exposures to the herbicide atrazine (ATRZ) were shown to suppress the LH surge in both cycling female rats and those ovariectomized (OVX) and primed with estradiol (E2). A single ATRZ administration was found to induce a prompt and marked increase in progesterone (P4). As exogenous P4 is known to have a differential effect on the LH surge depending on its temporal relationship with the surge, it was hypothesized that a single treatment in an OVX, E2-primed rat would augment the surge, whereas several exposures would cause a decrease. Following four daily treatments with 100 mg/kg, LH surge was suppressed. In contrast, a single ATRZ exposure elevated the surge. Two treatments were without effect. The single administration caused a large increase in P4 at 30 and 60 min that was likely attributable to adrenal secretion. Four exposures also elevated P4 after the final treatment, although the duration of the increase was shortened. A single treatment with 0, 10, 30, and 100 mg/kg ATRZ showed similar elevations at the highest concentration in P4, the LH peak, and area under the curve (AUC), whereas four exposures reduced the AUC. An increase at 1 h in the expression of Kiss1 in the anteroventral periventricular nucleus suggests that this regional kisspeptin neuronal population has a role in the ATRZ augmentation of the surge. These data support the hypothesis that ATRZ-induced changes in adrenal P4 can either augment or attenuate the surge depending on the temporal proximity of exposure to the rise in LH.
多次接触除草剂莠去津 (ATRZ) 被证明会抑制循环雌性大鼠和去卵巢并接受雌二醇 (E2) 预处理的大鼠的 LH 激增。单次 ATRZ 给药被发现会导致孕酮 (P4) 迅速而显著增加。由于外源性 P4 对 LH 激增的影响因其与激增的时间关系而异，因此假设在去卵巢、E2 预处理的大鼠中单次治疗会增强激增，而多次暴露会导致激增减少。在每日用 100mg/kg 进行四次治疗后，LH 激增受到抑制。相比之下，单次 ATRZ 暴露会升高激增。两次处理没有效果。单次给药会在 30 和 60 分钟时引起 P4 的大幅增加，这可能归因于肾上腺分泌。四次暴露也会在最后一次治疗后升高 P4，尽管增加的持续时间缩短了。单次给予 0、10、30 和 100mg/kg ATRZ 显示出相似的 P4、LH 峰值和曲线下面积 (AUC) 升高，而四次暴露降低了 AUC。在 1 小时时，前腹侧室旁核中 Kiss1 的表达增加表明，该区域 kisspeptin 神经元群体在 ATRZ 增强激增中起作用。这些数据支持这样的假设，即 ATRZ 诱导的肾上腺 P4 变化可以增强或减弱激增，具体取决于暴露与 LH 升高的时间接近程度。
