Veronikis I E, Alex S, Fang S L, Wright G, Wu S Y, Chanoine J P, Emerson C H, Braverman L E
Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA.
Eur J Endocrinol. 1996 Apr;134(4):519-23. doi: 10.1530/eje.0.1340519.
Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5'D-I activity is markedly decreased.
肠道细菌被认为可通过促进胆汁来源的甲状腺激素结合物的水解，从而在甲状腺代谢中发挥作用，进而使甲状腺素（T4）和三碘甲状腺原氨酸（T3）得以吸收和再循环。在I型碘甲状腺原氨酸脱碘酶活性（5'D-I）受到抑制的情况下，T3的肠肝循环可能会更加显著，因为这会增加胆汁中T3硫酸盐结合物的积累。T3肠道重吸收增加的这种可能性至少可以部分解释，当硒缺乏或给予6-苯胺基-2-硫脲（ATU）导致外周5'D-I活性显著降低时，血清T3值为何没有明显下降。因此，开展了相关研究，以确定在不存在和存在5'D-I抑制的情况下，肠道去污对血浆T4和T3浓度的影响。成年雄性大鼠分组，一组接受肠道抗生素治疗12天，另一组不接受抗生素治疗，然后在每组的一半大鼠中，用ATU治疗10天，ATU是一种不影响甲状腺激素合成的5'D-I抑制剂。无论是否同时接受ATU，接受抗生素治疗的大鼠中，催化甲状腺激素结合物水解的肠道芳基硫酸酯酶和芳基硫酸转移酶的活性均显著降低了约87%。ATU治疗显著抑制了抗生素治疗组和未接受抗生素治疗组（对照组）大鼠的肝脏5'D-I活性（对照组=399±32 U/mg蛋白质（平均值±标准误）；ATU组=152±17；抗生素组=351±29；抗生素+ATU组=130±10；p<0.01），并显著提高了血浆T4和T3硫酸盐（T4S、T3S）浓度（对照组：T4S=2.8±0.4，T3S=6.7±1.3 ng/dl；ATU组：T4S=6.2±1.4，T3S=10.6±2.1 ng/dl；抗生素组：T4S=1.8±0.2，T3S=3.6±1.0 ng/dl；抗生素+ATU组：T4S=6.8±0.7，T3S=9.7±1.8 ng/dl；p<0.05）。ATU治疗使血浆T4和反T3浓度显著升高，但不影响血浆T3浓度，肠道去污也未改变ATU对循环甲状腺激素的这些影响。这些结果表明，大鼠体内的厌氧肠道细菌在甲状腺激素再循环中，无论是在正常情况下还是在5'D-I活性显著降低的情况下，都没有重要作用，并且T3从T3S增加的肠道吸收不能解释当外周5'D-I活性显著降低时血清T3值接近正常的现象。
