2,2',4,4',5,5'- and 3,3',4,4',5,5'-hexachlorobiphenyl alteration of uterine progesterone and estrogen receptors coincides with embryotoxicity in mink (Mustela vision).
2,2',4,4',5,5'- and 3,3',4,4',5,5'-hexachlorobiphenyl alteration of uterine progesterone and estrogen receptors coincides with embryotoxicity in mink (Mustela vision).
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子宫孕酮和雌激素受体的 2,2,4,4,5,5- 和 3,3,4,4,5,5-六氯联苯改变与水貂的胚胎毒性一致（Mustela 视觉）。
DOI：
10.1006/taap.1994.1133
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发表时间：
1994
影响因子：
3.8
通讯作者：
Curtis,LR
中科院分区：
文献类型：
--
作者：
Patnode,KA;Curtis,LR
雌性水貂（Mustela vison）对有机氯（OC）引起的生殖损伤高度敏感。然而，这种生殖毒性的机制尚不清楚。我们已经研究了类固醇受体在胚胎毒性和减少新生儿体重中的可能作用。未发情的雌性水貂和怀孕的成年水貂暴露于3,3 ',4,4 ',5,5 ' -六氯联苯（3HCB），共面多氯联苯（PCB），或2,2 ',4,4 ',5,5 ' -六氯联苯（2HCB），非共面PCB同族物。两种同族基因均破坏了17 β -雌二醇刺激（100 μg E2β ip后24小时）的失情水貂细胞核雌激素受体（ERn）上调。在接触0.4 mg 3HCB/kg、0.8 mg 3HCB/kg、20 mg 2HCB/kg后第14天，首次观察到胚胎毒性和胚胎生长下降。在妊娠水貂中，所有3HCB处理均显著增加孕酮受体解离常数（PR Kd）。ER浓度和PR总受体数（Rt）分别增加20 mg 2HCB/kg和0.8 mg 3HCB/kg，但未受0.4 mg 3HCB/kg的影响。血清E2β低于检测限。孕酮(P)浓度增加2HCB，降低0.8 mg 3HCB/kg, 0,4 mg 3HCB/kg不变。3HCB对妊娠水貂的肝细胞色素P450 （P450）的诱导作用是妊娠水貂的2.2倍，妊娠水貂的1.8倍。雌水貂和妊娠水貂的乙氧基间苯二酚- o -去乙基酶（EROD）分别达到13倍和4倍。2HCB暴露导致无情幼体P450浓度降低，但对妊娠期P450和EROD活性均无影响。我们认为胚胎毒性和胚胎发育迟缓是由于PR功能受损造成的，而HCB治疗效果的差异是由于它们的剂量依赖性，部分雌激素作用通过上调ER来增加PR rt0。
Female mink (Mustela vison) are highly sensitive to organochlorine (OC)-induced reproductive impairment. However, mechanisms of this reproductive toxicity are unknown. We have investigated the possible role of steroid receptors in embryotoxicity and reduced neonate weights. Anestrous, juvenile female mink and pregnant adult mink were exposed to 3,3′,4,4′,5,5′-hexachlorobiphenyl (3HCB), a coplanar polychlorinated biphenyl (PCB), or 2,2′,4,4′,5,5′-hexachlorobiphenyl (2HCB), a noncoplanar PCB congener. Both congeners impaired 17 beta-estradiol-stimulated (24 hr after ip administration of 100 μg E2β ip) up-regulation of uterine nuclear estrogen receptors (ERn) in anestrous mink. Embryotoxicity and reduced embryo growth were first observed 14 days after exposure to 0.4 mg 3HCB/kg > 0.8 mg 3HCB/kg > 20 mg 2HCB/kg. In pregnant mink, all 3HCB treatments significantly increased progesterone receptor dissociation constants (PR Kd). ER concentration and PR total receptor number (Rt) were increased by 20 mg 2HCB/kg > 0.8 mg 3HCB/kg, but were unaffected by 0.4 mg 3HCB/kg. Serum E2β was below assay detection limits. Progesterone (P) concentrations were increased by 2HCB, decreased by 0.8 mg 3HCB/kg, and unchanged by 0,4 mg 3HCB/kg. Hepatic cytochrome P450 (P450) was induced 1.8-fold in anestrous and 2.2-foId in pregnant mink by 3HCB. Ethoxyresorufin-O-deethylase (EROD) was induced 13- and 4-fold in anestrous and pregnant mink, respectively. 2HCB exposure resulted in decreased P450 concentration in anestrous juveniles, but had no effect on P450 during gestation or EROD activity at any time. We propose that embryotoxicity and retarded embryo growth result from impairment of PR function and that differences in the efficacy of HCB treatments are a result of their dose-dependent, partial estrogenic actions which increase PR Rtvia up-regulation of ER.