Rooda S J, Kaptein E, Rutgers M, Visser T J
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Endocrinology. 1989 Feb;124(2):740-5. doi: 10.1210/endo-124-2-740.
In contrast to the glucuronide conjugate, T3 sulfate (T3S) undergoes rapid deiodinative degradation in the liver and accumulates in rats and rat hepatocyte cultures if type I iodothyronine deiodinase activity is inhibited. We here report the RIA of plasma T3S in rats treated with the antithyroid drugs propylthiouracil (PTU) or methimazole (MMI), of which only PTU inhibits type I deiodinase. Male Wistar rats were treated acutely by ip injection with 1 mg PTU or MMI/100 g BW and subsequently for 4 days by twice daily injections with these drugs together with 0.5 microgram T4 or 0.25 microgram T3/100 g BW. Blood was obtained 4 h after the last injection, and plasma T4, rT3, T3, and T3S were determined by RIA and compared with pretreatment values. Serum concentrations (mean +/- SEM; nanomoles per liter) in untreated rats were: T4, 51 +/- 1; T3, 1.37 +/- 0.03; T3S, 0.09 +/- 0.01; and rT3, 0.03 +/- 0.002. Serum T3 was decreased, and T3S and rT3 were increased by acute PTU treatment [T3, 1.16 +/- 0.05 (P less than 0.01); T3S, 0.33 +/- 0.04 (P less than 0.001); rT3, 0.27 +/- 0.02 (P less than 0.001)], but unaffected by acute MMI treatment (T3, 1.37 +/- 0.05; T3S, 0.09 +/- 0.01; rT3, 0.02 +/- 0.003). In T4-treated rats, serum T3 was decreased and T4, T3S, and rT3 were increased by PTU vs. MMI [T4, 86 +/- 5 vs. 58 +/- 4 (P less than 0.001); T3, 0.51 +/- 0.07 vs. 0.88 +/- 0.06 (P less than 0.001); T3S, 0.38 +/- 0.03 vs. 0.12 +/- 0.01 (P less than 0.001); rT3, 0.86 +/- 0.19 vs. 0.08 +/- 0.01 (P less than 0.005)]. In T3-substituted rats T3S was increased by PTU vs. MMI (1.09 +/- 0.13 vs. 0.25 +/- 0.03; P less than 0.001). The T3S/T3 ratio in the PTU-treated T3 -replaced rats (0.60 +/- 0.09) was in agreement with that determined by HPLC of serum radioactivity in animals that in addition to this treatment also received about 10 microCi [125I]T3 with the last two injections (0.92 +/- 0.13). In conclusion, this investigation demonstrates the feasibility of the measurement of serum T3S by RIA. Our findings confirm previous observations with radioactive isotopes, suggesting that sulfation is an important pathway for the metabolism of T3 in rats. Analogous to rT3, the accumulation of T3S in PTU-treated rats indicates that this conjugate is metabolized predominantly by type I deiodination.
与葡萄糖醛酸结合物不同，硫酸化三碘甲状腺原氨酸（T3S）在肝脏中经历快速脱碘降解，并且如果I型碘甲状腺原氨酸脱碘酶活性受到抑制，它会在大鼠和大鼠肝细胞培养物中积累。我们在此报告用抗甲状腺药物丙硫氧嘧啶（PTU）或甲巯咪唑（MMI）处理的大鼠血浆T3S的放射免疫分析（RIA），其中只有PTU抑制I型脱碘酶。雄性Wistar大鼠通过腹腔注射1mg PTU或MMI/100g体重进行急性处理，随后连续4天每天两次注射这些药物以及0.5μg T4或0.25μg T3/100g体重。在最后一次注射后4小时采集血液，通过RIA测定血浆T4、反式三碘甲状腺原氨酸（rT3）、T3和T3S，并与预处理值进行比较。未处理大鼠的血清浓度（平均值±标准误；纳摩尔/升）为：T4，51±1；T3，1.37±0.03；T3S，0.09±0.01；rT3，0.03±0.002。急性PTU处理使血清T3降低，T3S和rT3升高[T3，1.16±0.05（P＜0.01）；T3S，0.33±0.04（P＜0.001）；rT3，0.27±0.02（P＜0.001）]，但不受急性MMI处理影响（T3，1.37±0.05；T3S，0.09±0.01；rT3，0.02±0.003）。在T4处理的大鼠中，与MMI相比，PTU使血清T3降低，T4、T3S和rT3升高[T4，86±5对58±4（P＜0.001）；T3，0.51±0.07对0.88±0.06（P＜0.001）；T3S，0.38±0.03对0.12±0.01（P＜0.001）；rT3，0.86±0.19对0.08±0.01（P＜0.005）]。在T3替代的大鼠中，与MMI相比，PTU使T3S升高（1.09±0.13对0.25±0.03；P＜0.001）。PTU处理的T3替代大鼠中的T3S/T3比值（0.60±0.09）与通过高效液相色谱法（HPLC）测定的动物血清放射性比值一致，这些动物除了这种处理外，在最后两次注射时还接受了约10微居里[125I]T3（0.92±0.13）。总之，本研究证明了通过RIA测量血清T3S的可行性。我们的发现证实了先前用放射性同位素的观察结果，表明硫酸化是大鼠中T3代谢的重要途径。与rT3类似，PTU处理的大鼠中T3S的积累表明这种结合物主要通过I型脱碘代谢。
