Atrazine disrupts the hypothalamic control of pituitary-ovarian function
Atrazine disrupts the hypothalamic control of pituitary-ovarian function
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DOI：
10.1093/toxsci/53.2.297
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发表时间：
2000-02-01
影响因子：
3.8
通讯作者：
McElroy, WK
中科院分区：
文献类型：
--
作者：
Cooper, RL;Stoker, TE;McElroy, WK
氯- s -三嗪类除草剂（即阿特拉津、西马津、氰嗪）是在美国销售的最大一类除草剂。尽管它们被广泛使用，但对这些化合物可能对人类健康的影响和作用机制所知相对较少。我们实验室以前的研究表明，氯三嗪类药物会破坏卵巢周期的激素控制。这些研究的结果使我们假设这些除草剂主要通过对中枢神经系统的作用来破坏内分泌功能。为了验证这一假设，我们对去卵巢的Sprague-Dawley （SD）和lang - evans hood （LE）大鼠给予阿特拉津（50-300 mg/kg/天，灌胃）1、3和21天，观察了雌激素诱导的促黄体生成素（LH）和催乳素的激增。1剂量阿特拉津（300 mg/kg）可抑制LE去卵巢雌性大鼠LH和催乳素的升高，但对SD大鼠无抑制作用。在阴道发情当天给药阿特拉津（300 mg/kg）对正常LE雌性没有影响排卵，但在9只雌性中有7只诱导了假妊娠。每日三剂量的阿特拉津抑制卵巢切除的LE女性雌激素诱导的LH和催乳素激增呈剂量依赖性，但同样的治疗对SD女性血清LH和催乳素没有影响。阿特拉津（75 ~ 300 mg/kg/天）对雌性小鼠雌激素诱导的两种垂体激素的抑制呈剂量依赖性。然后进行了三个实验来确定脑、垂体或两个器官是否是氯三嗪的靶点，这些实验包括检查(1)垂体乳滋养细胞分泌催乳素的能力，使用垂体切除的女性携带垂体自体移植（异位垂体）；(2)合成促性腺激素释放激素（GnRH）诱导高浓度阿特拉津处理3天的雌性黄体生成素分泌；(3)阿特拉津（体内或体外）通过血流灌注法抑制垂体LH和催乳素分泌。综上所述，这些研究结果表明，阿特拉津通过改变下丘脑对LH和催乳素的控制来改变LE和SD雌性大鼠血清LH和催乳素水平。在这方面，LE雌性似乎对阿特拉津的激素抑制作用更敏感，正如治疗第3天观察到的下降所表明的那样。这些实验支持了阿特拉津对LH和催乳素分泌的影响是通过下丘脑作用部位介导的假设。
The chloro-S-triazine herbicides (i.e., atrazine, simazine, cyanazine) constitute the largest group of herbicides sold in the United States. Despite their extensive usage, relatively little is known about the possible human-health effects and mechanism(s) of action of these compounds. Previous studies in our laboratory have shown that the chlorotriazines disrupt the hormonal control of ovarian cycles. Results from these studies led us to hypothesize that these herbicides disrupt endocrine function primarily through their action on the central nervous system. To evaluate this hypothesis, we examined the estrogen-induced surges of luteinizing hormone (LH) and prolactin in ovariectomized Sprague-Dawley (SD) and Long-Evans hooded (LE) rats treated with atrazine (50-300 mg/kg/day, by gavage) for 1, 3, or 21 days. One dose of atrazine (300 mg/kg) suppressed the LH and prolactin surge in ovariectomized LE, but not SD female rats. Atrazine (300 mg/kg) administered to intact LE females on the day of vaginal proestrus was without effect on ovulation but did induce a pseudopregnancy in 7 of 9 females. Three daily doses of atrazine suppressed the estrogen-induced LH and prolactin surges in ovariectomized LE females in a dose-dependent manner, but this same treatment was without effect on serum LH and prolactin in SD females. The estrogen-induced surges of both pituitary hormones were suppressed by atrazine (75-300 mg/kg/day) in a dose-dependent manner in females of both strains evaluated after 21 days of treatment. Three experiments were then performed to determine whether the brain, pituitary, or both organs were the target sites for the chlorotriazines, These included examination of the ability of (1) the pituitary lactotrophs to secrete prolactin, using hypophyosectomized females bearing pituitary autotransplants (ectopic pituitaries); (2) the synthetic gonadotropin-releasing hormone (GnRH) to induce LH secretion in females treated with high concentrations of atrazine for 3 days; and (3) atrazine (administered in vivo or in vitro) to suppress LH and prolactin secretion from pituitaries, using a flow-through perifusion procedure, In conclusion, the results of these studies demonstrate that atrazine alters LH and prolactin serum levels in the LE and SD female rats by altering the hypothalamic control of these hormones. In this regard, the LE female appeared to be more sensitive to the hormone suppressive effects of atrazine, as indicated by the decreases observed on treatment-day 3. These experiments support the hypothesis that the effect of atrazine on LH and prolactin secretion is mediated via a hypothalamic site of action.