Atrazine Inhibits Pulsatile Luteinizing Hormone Release Without Altering Pituitary Sensitivity to a Gonadotropin-Releasing Hormone Receptor Agonist in Female Wistar Rats
Atrazine Inhibits Pulsatile Luteinizing Hormone Release Without Altering Pituitary Sensitivity to a Gonadotropin-Releasing Hormone Receptor Agonist in Female Wistar Rats
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DOI：
10.1095/biolreprod.108.075713
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发表时间：
2009-07-01
影响因子：
3.6
通讯作者：
Handa, Robert J.
中科院分区：
文献类型：
--
作者：
Foradori, Chad D.;Hinds, Laura R.;Handa, Robert J.
阿特拉津[2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine]]是美国最常用的除草剂之一。阿特拉津已被证明可以抑制黄体生成素的释放，并能导致大鼠发情周期的延长。本研究的目的是观察阿特拉津对黄体生成素正常的紧张性释放的影响，并阐明阿特拉津在下丘脑-垂体-性腺轴的作用部位。促性腺激素释放激素(GnRH)的间歇性释放和相应的促黄体生成素(LH)的释放是正常生殖功能所必需的。为确定阿特拉津是否影响黄体生成素的脉动性释放，成年雌性Wistar大鼠去卵巢后给予阿特拉津(50、100、200 mg/kg体重，每天灌胃)或溶剂对照组，连续4天。在阿特拉津治疗的最后一天，通过留置右心房插管采集血样。在接受200 mg/kg剂量组中，黄体生成素脉冲频率显著降低，脉冲幅度显著增加。为了确定阿特拉津对促黄体生成素释放的影响是否是由于垂体水平的变化，动物被内源性GnRH被动免疫，用阿特拉津治疗，并用GnRH受体激动剂激发。阿特拉津在任何剂量下都不能改变垂体对GnRH受体激动剂的敏感性。综上所述，这些发现表明，高剂量的阿特拉津影响大脑中的GnRH脉冲发生器，而不是在脑垂体中促性腺激素的水平上。
Atrazine [2- chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine] is one of the most commonly used herbicides in the United States. Atrazine has been shown to suppress luteinizing hormone (LH) release and can lead to a prolongation of the estrous cycle in the rat. The objectives of this study were to examine the effects of atrazine on normal tonic release of LH and to elucidate the site of action of atrazine in the hypothalamic-pituitary-gonadal axis. Episodic release of gonadotropin-releasing hormone (GnRH) and the corresponding release of LH from the anterior pituitary gland are required for normal reproductive function. To determine if atrazine affects pulsatile LH release, ovariectomized adult female Wistar rats were administered atrazine (50, 100, or 200 mg/kg of body weight daily by gavage) or vehicle control for 4 days. On the final day of atrazine treatment, blood samples were obtained using an indwelling right atrial cannula. In the group receiving 200 mg/kg, there was a significant reduction in LH pulse frequency and a concomitant increase in pulse amplitude. To determine if the effects of atrazine on LH release were due to changes at the level of the pituitary, animals were passively immunized against endogenous GnRH, treated with atrazine, and challenged with a GnRH receptor agonist. Atrazine failed to alter pituitary sensitivity to the GnRH receptor agonist at any dose used. Taken together, these findings demonstrate that high doses of atrazine affect the GnRH pulse generator in the brain and not at the level of gonadotrophs in the pituitary.