Khan Moazzam A, Lichtensteiger Carol A, Faroon Obaid, Mumtaz Moiz, Schaeffer David J, Hansen Larry G
Department of Veterinary Biosciences, College of Veterinary Medicine, 2001 S. Lincoln Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
Toxicol Sci. 2002 Jan;65(1):52-61. doi: 10.1093/toxsci/65.1.52.
Coplanar polychlorinated biphenyls (PCBs) cause adverse effects in developing and adult animals. Less is known about the effects of nonplanar ortho-substituted PCBs. We investigated the effects of 2 nonplanar PCB congeners, 95 (2,3,6-2',5'-penta CB) or 101 (2,4,5-2',5'-penta CB), and estradiol on selected endocrine parameters. In Study 1, weanling female Sprague-Dawley (S-D) rats were given a single dose of PCB 95 ip at 4, 8, 16, and 32 mg/kg/day for 2 consecutive days and killed 24 h after the last dose. PCB 95 exposure caused a dose-dependent (p < 0.001) decrease in serum thyroxine (T4) levels. Serum thyroid stimulating hormone (TSH) concentrations did not change, but prolactin (PRL) levels increased in a nonlinear (with dose) manner. No significant changes were seen in thyroid gland morphology and pituitary lactotroph number. In Study 2, progression or regression of effects was assessed by lengthening the time and a second congener was tested. Weanling female S-D rats received a single dose of PCB 95 or PCB 101 ip at 16 and 32 mg/kg/day for 2 days and were killed 48 h after the last dose. PCB 95 and PCB 101 both decreased serum T4 (p < 0.001) and hypothalamic dopamine (DA; p < 0.05) levels. No changes were seen in serum triiodothyronine (T3), TSH, and PRL concentrations. Morphological analysis of the thyroid gland showed a decrease (p < 0.05) in colloid area in rats treated with PCB 95 or 101. However, the epithelial cell height increased only in PCB 95 treated rats. Thyroid epithelial cell proliferation increased (p < 0.05) following exposure to estradiol and PCB 95. The results suggest that the HPT axis appears to be a target of ortho-substituted PCBs. PCB 95 was more effective than PCB 101 in causing these changes.
共平面多氯联苯（PCBs）会对发育中的动物和成年动物产生不良影响。关于非平面邻位取代多氯联苯的影响，人们了解得较少。我们研究了两种非平面多氯联苯同系物，即95号（2,3,6 - 2',5'-五氯联苯）或101号（2,4,5 - 2',5'-五氯联苯）以及雌二醇对选定内分泌参数的影响。在研究1中，给断乳雌性斯普拉格 - 道利（S - D）大鼠连续2天腹腔注射单剂量的95号多氯联苯，剂量分别为4、8、16和32毫克/千克/天，在最后一剂后24小时处死。暴露于95号多氯联苯导致血清甲状腺素（T4）水平呈剂量依赖性下降（p < 0.001）。血清促甲状腺激素（TSH）浓度未发生变化，但催乳素（PRL）水平呈非线性（与剂量相关）升高。甲状腺形态和垂体催乳细胞数量未见明显变化。在研究2中，通过延长时间来评估效应的进展或消退，并测试了另一种同系物。断乳雌性S - D大鼠腹腔注射单剂量的95号或101号多氯联苯，剂量为16和32毫克/千克/天，共2天，在最后一剂后48小时处死。95号和101号多氯联苯均降低了血清T4（p < 0.001）和下丘脑多巴胺（DA；p < 0.05）水平。血清三碘甲状腺原氨酸（T3）、TSH和PRL浓度未见变化。对甲状腺的形态学分析显示，用95号或101号多氯联苯处理的大鼠甲状腺胶体面积减少（p < 0.05）。然而，仅在95号多氯联苯处理的大鼠中上皮细胞高度增加。暴露于雌二醇和95号多氯联苯后甲状腺上皮细胞增殖增加（p < 0.05）。结果表明，下丘脑 - 垂体 - 甲状腺（HPT）轴似乎是邻位取代多氯联苯的作用靶点。在引起这些变化方面，95号多氯联苯比101号多氯联苯更有效。
