Pine Michelle D, Hiney Jill K, Lee Boyeon, Dees W Les
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77843-4458, USA.
Environ Health Perspect. 2008 Sep;116(9):1243-7. doi: 10.1289/ehp.11119.
One of the most widely used classes of insecticides is the synthetic pyrethroids. Although pyrethroids are less acutely toxic to humans than to insects, in vitro studies have suggested that pyrethroids may be estrogenic.
We assessed pubertal effects by orally administering 0.5, 1.0, and 5.0 mg/kg/day of the type II pyrethroid esfenvalerate (ESF) to female rats beginning on postnatal day (PND) 22 until vaginal opening. ESF administration suppresses serum estradiol and delays pubertal onset.
To assess possible hypothalamic and/or pituitary effects, animals received 0.5 or 1.0 mg/kg ESF or corn oil on PNDs 22-29. On PND30, we drew three blood samples (200 microL) from each rat at 15-min intervals beginning at 1000 hours, and again at 1500 hours. To test hypothalamic responsiveness, after the third afternoon sample, all animals received an intravenous injection of N-methyl-d,l-aspartic acid (NMA; 40 mg/kg), and then we drew two more samples. We performed a second experiment as above except that animals received luteinizing hormone-releasing hormone (LHRH; 25 ng/rat) to test pituitary responsiveness.
Basal levels of luteinizing hormone (LH) in the afternoon hours were higher in control animals than in animals treated with 1.0 mg/kg ESF (p < 0.05). Furthermore, NMA- and LHRH-stimulated LH release was similar in control and ESF-treated animals, indicating that both hypothalamic and pituitary responsiveness, respectively, were unaffected.
Although the hypothalamus is able to respond to exogenous stimuli, absence of a normal afternoon rise in LH would indicate a hypothalamic deficit in ESF-treated animals.
合成拟除虫菊酯是使用最为广泛的一类杀虫剂。尽管拟除虫菊酯对人类的急性毒性低于对昆虫的毒性,但体外研究表明拟除虫菊酯可能具有雌激素活性。
从出生后第22天(PND)开始,对雌性大鼠每日经口给予0.5、1.0和5.0 mg/kg的II型拟除虫菊酯乙氰菊酯(ESF),直至阴道开口,以此评估其对青春期的影响。给予ESF会抑制血清雌二醇水平并延迟青春期开始。
为评估可能对下丘脑和/或垂体产生的影响,在出生后第22至29天,动物接受0.5或1.0 mg/kg ESF或玉米油处理。在出生后第30天,从每只大鼠身上于10:00开始每隔15分钟采集三份血样(200微升),15:00时再次采集。为测试下丘脑反应性,在第三次下午血样采集后,所有动物接受静脉注射N-甲基-D,L-天冬氨酸(NMA;40 mg/kg),然后再采集两份血样。我们进行了第二项实验,除动物接受促黄体生成素释放激素(LHRH;25 ng/只大鼠)以测试垂体反应性外,其余与上述实验相同。
下午时段,对照动物的促黄体生成素(LH)基础水平高于接受1.0 mg/kg ESF处理的动物(p < 0.05)。此外,对照动物和接受ESF处理的动物中,NMA和LHRH刺激的LH释放相似,这分别表明下丘脑和垂体的反应性均未受影响。
尽管下丘脑能够对外源刺激作出反应,但ESF处理的动物中LH在下午未出现正常升高,这表明存在下丘脑功能缺陷。