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首页> 外文期刊>Environmental Health Perspectives >ENVIRONMENTAL XENOBIOTICS MAY DISRUPT NORMAL ENDOCRINE FUNCTION BY INTERFERING WITH THE BINDING OF PHYSIOLOGICAL LIGANDS TO STEROID RECEPTORS AND BINDING PROTEINS
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ENVIRONMENTAL XENOBIOTICS MAY DISRUPT NORMAL ENDOCRINE FUNCTION BY INTERFERING WITH THE BINDING OF PHYSIOLOGICAL LIGANDS TO STEROID RECEPTORS AND BINDING PROTEINS

机译:环境异种药物可能会干扰生理性液体与类固醇受体和蛋白质的结合,从而破坏正常的内分泌功能

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The disruption of the reproductive system of male and female animals in the wild has been attributed to environmental chemicals (xenobiotics). The effects seen mirror alterations one might anticipate if the steroid hormone-dependent processes chat regulate these systems were impaired. To determine whether xenobiotics (present at a concentration of 100 mu M) exert their action through steroid-mediated pathways, we examined their ability to inhibit the binding of [H-3]physiological ligands (present at a concentration of 7 nM) to the androgen and estrogen receptors, rat androgen-binding protein (ABP), and human sex hormone-binding globulin (hSHBG). The gamma- and delta-isomers of hexachlorocyclohexane, congeners of dichlorodiphenyltrichloroethane (DDT; p,p'-DDT; p,p'-DDE; o,p'-DDT), dieldrin, atrazine, and pentachlorophenol, caused a statistically significant inhibition of specific binding of [H-3]5 alpha-DHT to the androgen receptor that ranged from 100% (p,p'-DDE) to 25% (dieldrin). Methoxychlor, o,p'-DDT, pentachlorophenol, and nonylphenol significantly reduced [H-3]17 beta-estradiol binding to the estrogen receptor by 10, 60, 20, and 75%, respectively. The binding of [H-3]5 alpha-DHT to ABP was inhibited 70% by the delta-isomer of hexachlorocyclohexane, but the gamma-isomer did not reduce binding significantly. Methoxychlor, p,p'-DDT, atrazine, and nonylphenol reduced [H-3]5 alpha-DHT binding to ABP by approximately 40%. Nonylphenol reduced the binding of [H-3]5 alpha-DHT to hSHBG by 70%. Hexachlorocyclohexane reduced [H-3]5 alpha-DHT binding to hSHBG by 20%, but the stereospecific effects observed with ABP did not occur. o,p'-DDT and pentachlorophenol resulted in a statistically significant 20% inhibition of [H-3]5 alpha-DHT binding to hSHBG. Some xenobiotics resulted in dissociation of [H-3]ligands from their binding proteins that was statistically identical to that caused by the unlabeled natural ligand, whereas others resulted in slower or more rapid dissociation rates. [References: 42]
机译:野外雄性和雌性动物生殖系统的破坏被归因于环境化学物质(异生物素)。如果视类固醇激素依赖的过程调节这些系统受损,则可以预见镜子改变的效果。为了确定异种生物(浓度为100μM)是否通过类固醇介导的途径发挥作用,我们检查了它们抑制[H-3]生理性配体(浓度为7 nM)与药物结合的能力。雄激素和雌激素受体,大鼠雄激素结合蛋白(ABP)和人性激素结合球蛋白(hSHBG)。六氯环己烷的γ-异构体和δ-异构体,二氯二苯基三氯乙烷(DDT; p,p'-DDT; p,p'-DDE; o,p'-DDT),狄氏剂,at去津和五氯苯酚的同类物引起统计学上显着的抑制作用[H-3]5α-DHT与雄激素受体的特异性结合的比例为100%(p,p'-DDE)至25%(狄氏剂)。甲氧氯,o,p'-DDT,五氯苯酚和壬基苯酚分别将[H-3] 17β-雌二醇与雌激素受体的结合作用分别降低了10%,60%,20%和75%。 [H-3] 5α-DHT与ABP的结合被六氯环己烷的δ-异构体抑制了70%,但γ-异构体并未显着降低结合。甲氧氯,p,p'-DDT,at去津和壬基酚使[H-3] 5α-DHT与ABP的结合降低约40%。壬基酚使[H-3] 5α-DHT与hSHBG的结合降低了70%。六氯环己烷使[H-3] 5α-DHT与hSHBG的结合降低了20%,但未发生ABP所观察到的立体定向作用。 o,p'-DDT和五氯苯酚对[H-3] 5 alpha-DHT与hSHBG的结合产生了统计上显着的20%抑制作用。一些外源生物导致[H-3]配体从其结合蛋白上解离,这在统计学上与未标记的天然配体引起的解离相同,而另一些导致了更慢或更快速的解离速率。 [参考:42]

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