Organotin compounds (OTs) act as potent endocrine disruptors that are often found in polluted food and water. UDP-glucuronosyltransferases (UGTs) are responsible for termination of multiple endogenous hormones. This study was conducted to investigate the inhibitory effects of two tri-submitted OTs tributyltin (TBT) and triphenyltin (TPT), against activities of UGTs. It is revealed that TBT and TPT act as two potent inhibitors for multiple UGTs. UGT1A8 and -2B15 were coinhibited by the two OTs. UGT1A1 and -1A10 were inhibited by TPT, whereas UGT 2B4 and -2B7 were inhibited by TBT. Kinetic analyses further indicated that TBT and TPT are two competitive nanomolar inhibitors of UGT2B15, with K_i values of 0.45 and 0.46 μM, respectively. K_i values for the other UGTs are determined to be a few micromolars. In addition, the two OTs displayed effective inhibition against UGT2B15 in catalyzing dihydrotestosterone glucuronidation, with IC50 values both in nano-molar range. TPT can additionally inhibit activities of UGT1A1 and -1A10 in estradiol-3-O-glucuronidation, with IC50 values of a few micro-molars. These results indicated that the two OTs can extensively interfere with glucuronidation of endogenous hormones, which may act as a new potential mechanism resulting in endocrine disrupting actions.

有机锡化合物（OTs）充当有效的内分泌干扰物，通常在受污染的食物和水中被发现。UDP-葡萄糖醛酸转移酶（UGT）负责终止多种内源激素。进行本研究以研究两种三价OTs三丁基锡（TBT）和三苯基锡（TPT）对UGT活性的抑制作用。揭示了TBT和TPT充当多种UGT的两种有效抑制剂。UGT1A8和-2B15被这两个OT共同禁止。TGT抑制UGT1A1和-1A10，而TBT抑制UGT 2B4和-2B7。动力学分析进一步表明，TBT和TPT是UGT2B15的两种竞争性纳摩尔抑制剂，K _i值分别为0.45和0.46μM。ķ_我其他UGT的值确定为几微摩尔。另外，两个OTs在催化二氢睾丸激素葡萄糖醛酸化中显示出对UGT2B15的有效抑制，IC50值均在纳摩尔范围内。TPT还可以抑制雌二醇-3-O-葡萄糖醛酸糖苷化中UGT1A1和-1A10的活性，IC50值为几微摩尔。这些结果表明，两个OT可以广泛干扰内源激素的葡萄糖醛酸苷化，这可能是导致内分泌干扰作用的新的潜在机制。