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三丁基锡暴露后河口糠虾(甲壳纲;糠虾目)体内的睾酮代谢

Testosterone metabolism in the estuarine mysid Neomysis integer (Crustacea; Mysidacea) following tributyltin exposure.

作者信息

Verslycke Tim, Poelmans Sofie, De Wasch Katia, Vercauteren Jordy, Devos Christophe, Moens Luc, Sandra Patrick, De Brabander Hubert F, Janssen Colin R

机构信息

Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent, Belgium.

出版信息

Environ Toxicol Chem. 2003 Sep;22(9):2030-6.

Abstract

Current evidence suggests that the biocide tributyltin (TBT) causes the development of imposex, a state of pseudohermaphrodism in which females exhibit functional secondary male characteristics, by altering the biotransformation or elimination of testosterone. Imposex in gastropods following TBT exposure is the most complete example of the effects of an endocrine disrupter on marine invertebrates. Previous studies have demonstrated that the estuarine mysid Neomysis integer converts testosterone into multiple polar and nonpolar metabolites resulting from both phase I and phase II biotransformations. In this study, the effects of TBT chloride (TBTCl) on the phase I and II testosterone metabolism of N. integer were evaluated. The TBTCl was highly toxic to N. integer (96-h median lethal concentration [LC50] of 164 ng/L). To assess the effects on testosterone metabolism, mysids were exposed for 96 h to different concentrations of TBTCl (control, 10, 100, and 1,000 ng/L), and testosterone elimination as polar hydroxylated, nonpolar oxido-reduced, and glucose- and sulfate-conjugated metabolites was examined. The TBTCl differentially affected testosterone metabolism. The effect of TBTCl on phase I metabolism was unclear and has been shown to vary among species, likely depending on the inducibility or presence of certain P450 isozyme families. Reductase activity and metabolic androgenization were induced in the 10-ng/L treatment, whereas higher concentrations resulted in a reduction of sulfate conjugation. The exact mechanisms underlying TBT-induced imposex and alterations in the steroid metabolism need to be further elucidated.

摘要

目前的证据表明,杀生物剂三丁基锡(TBT)通过改变睾酮的生物转化或消除过程,导致了性畸变的发生,性畸变是一种假两性畸形状态,其中雌性表现出功能性的第二性征。TBT暴露后腹足类动物出现的性畸变是内分泌干扰物对海洋无脊椎动物影响的最典型例子。先前的研究表明,河口糠虾Neomysis integer能将睾酮转化为多种由I相和II相生物转化产生的极性和非极性代谢产物。在本研究中,评估了氯化三丁基锡(TBTCl)对Neomysis integer睾酮I相和II相代谢的影响。TBTCl对Neomysis integer具有高毒性(96小时半数致死浓度[LC50]为164 ng/L)。为了评估对睾酮代谢的影响,将糠虾暴露于不同浓度的TBTCl(对照组、10、100和1000 ng/L)96小时,并检测睾酮作为极性羟基化、非极性氧化还原以及葡萄糖和硫酸盐结合代谢产物的消除情况。TBTCl对睾酮代谢有不同影响。TBTCl对I相代谢的影响尚不清楚,并且已表明在不同物种间存在差异,这可能取决于某些P450同工酶家族的可诱导性或存在情况。在10 ng/L处理组中诱导了还原酶活性和代谢雄激素化,而较高浓度则导致硫酸盐结合减少。TBT诱导性畸变和类固醇代谢改变的具体机制需要进一步阐明。

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