Goldman J M, Stoker T E, Perreault S D, Cooper R L, Crider M A
Reproductive Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Toxicol Appl Pharmacol. 1993 Aug;121(2):279-90. doi: 10.1006/taap.1993.1155.
The formamidine pesticide chlordimeform (CDF) has been found to interfere with the hormonal control of ovulation in the rat by a presumptive disruption in the catecholaminergic regulation of the midcycle surge of luteinizing hormone (LH). While the brain hypothalamic mechanisms underlying generation of the hamster surge have not been as well-defined, there is evidence for an adrenergic component. The present experiments were designed to investigate the effects of CDF on ovulation in the golden hamster and whether any observed alterations are associated with differences in the appearance of the surge. Intraperitoneal CDF injections (0, 75, 150, or 200 mg/kg) at 1400 hr on proestrus caused a dose-related reduction in oocytes retrieved at 0700 hr on the day of estrus. Additional experiments demonstrated that this effect was due to a delay in ovulation and not a decrease in the complement of oocytes released. Doses of 150 or 200 mg/kg at 1100 hr or 200 mg/kg at 1600 hr were without a comparable ovulatory effect. Characterization of the LH surge indicated that there was a dose-related delay, but that this effect was not sufficient to account for the delay in ovulation. Animals dosed at 1100 hr (150 or 200 mg/kg) exhibited shifts in the surge identical to those animals injected at 1400 hr, but did not show any such detectable effects on the time of oocyte release. CDF administered at 1100 or 1400 hr also caused alterations in serum estradiol and progesterone, even at a relatively low dose of 37.5 mg/kg. The results indicate that CDF given at a time just prior to the preovulatory rise in LH is able to impede ovulation in the hamster by possibly influencing some ovulatory event(s) triggered by the surge. Also, the ability of CDF to alter the timing of LH release is consistent with catecholaminergic participation in the generation of the gonadotropin signal stimulating the final events leading to ovulation. Under the present conditions, this perturbation can be characterized as a delay in the LH trigger, rather than a blockade.
已发现甲脒类杀虫剂杀虫脒（CDF）会干扰大鼠排卵的激素控制，推测其通过破坏促黄体生成素（LH）中期激增的儿茶酚胺能调节来实现。虽然仓鼠LH激增产生的脑下丘脑机制尚未明确，但有证据表明存在肾上腺素能成分。本实验旨在研究CDF对金黄仓鼠排卵的影响，以及观察到的任何变化是否与激增的出现差异有关。在发情前期14:00腹腔注射CDF（0、75、150或200mg/kg），导致在发情日07:00回收的卵母细胞数量呈剂量相关减少。额外实验表明，这种效应是由于排卵延迟，而非释放的卵母细胞数量减少。在11:00给予150或200mg/kg剂量或在16:00给予200mg/kg剂量均无类似的排卵效应。对LH激增的特征分析表明，存在剂量相关延迟，但这种效应不足以解释排卵延迟。在11:00给药（150或200mg/kg）的动物与在14:00注射的动物相比，激增出现了相同的变化，但对卵母细胞释放时间未显示出任何可检测到的影响。在11:00或14:00给予CDF，即使剂量相对较低（37.5mg/kg），也会导致血清雌二醇和孕酮发生变化。结果表明，在LH排卵前升高之前给予CDF能够通过可能影响由激增触发的某些排卵事件来阻碍仓鼠排卵。此外，CDF改变LH释放时间的能力与儿茶酚胺能参与促性腺激素信号生成一致，该信号刺激导致排卵的最终事件。在当前条件下，这种干扰可被描述为LH触发延迟，而非阻断。
