Eelkman Rooda S J, Kaptein E, Visser T J
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1989 Sep;69(3):552-6. doi: 10.1210/jcem-69-3-552.
In humans deiodination and perhaps glucuronidation are important pathways of thyroid hormone metabolism. In animals, sulfation plays an important role in T4 and especially in T3 metabolism, but little is known about sulfate conjugation of thyroid hormone in humans. In this study we used a specific T3 sulfate (T3S) RIA to address this question. Eight normal subjects were given oral T3 (1 microgram/day.kg BW) for 7 weeks. During the fifth week they also received propylthiouracil (PTU; four doses of 250 mg/day) for 2 days and during the seventh week iopanoic acid (IOP; 1 g/day) for 3 days. The mean pre-T3 serum iodothyronine values were: T4, 92 +/- 6 (+/- SE) nmol/L; rT3, 0.24 +/- 0.02 nmol/L; T3, 2.30 +/- 0.10 nmol/L; and T3S, less than 0.1 nmol/L (at or below the detection limit of the RIA). After 4 weeks of T3 administration the mean serum values were: T4, 39 +/- 6; rT3, 0.11 +/- 0.01; T3, 5.31 +/- 0.39; and T3S, 0.10 +/- 0.01 nmol/L. After 2 days of PTU administration, mean serum T4 increased to 48 +/- 7 (P less than 0.005), rT3 to 0.20 +/- 0.03 (P less than 0.025), and T3S to 0.13 +/- 0.01 nmol/L (P = NS), but serum T3 did not change (4.91 +/- 0.35 nmol/L). The effect of IOP was more pronounced; after its administration for 3 days the mean serum T4 was 49 +/- 8 (P less than 0.001), rT3 was 0.48 +/- 0.09 (P less than 0.005), and T3S was 0.29 +/- 0.04 nmol/L (P less than 0.005), and serum T3 decreased to 3.95 +/- 0.25 nmol/L (P less than 0.005). The T3S/T3 ratio was increased by PTU from 0.018 +/- 0.003 to 0.024 +/- 0.004 (P less than = NS) and by IOP to 0.055 +/- 0.007 (P less than 0.005). In conclusion, 1) serum T3S is virtually undetectable (less than 0.1 nmol/L) in normal subjects; 2) low serum T3S concentrations are detected in humans given T3; 3) serum T3S in T3-treated subjects is increased by inhibition of type I deiodinase activity with PTU and especially IOP; and 4) in comparison with previous estimates of the serum T3S/T3 ratio in rats, the low ratio in humans may indicate that sulfation is not an important mechanism of T3 metabolism in humans and/or the kinetics of plasma T3 and T3S differ in humans and rats.
在人类中,脱碘作用或许还有葡萄糖醛酸化作用是甲状腺激素代谢的重要途径。在动物中,硫酸化在T4尤其是T3的代谢中起重要作用,但关于甲状腺激素在人类中的硫酸结合作用却知之甚少。在本研究中,我们使用了一种特异性的T3硫酸盐(T3S)放射免疫分析法来解决这个问题。八名正常受试者口服T3(1微克/天·千克体重),持续7周。在第五周,他们还接受了丙硫氧嘧啶(PTU;每日4剂,每剂250毫克),共2天;在第七周,接受了碘番酸(IOP;1克/天),共3天。服用T3前血清甲状腺素的平均值为:T4,92±6(±标准误)纳摩尔/升;反T3,0.24±0.02纳摩尔/升;T3,2.30±0.10纳摩尔/升;T3S,低于0.1纳摩尔/升(处于或低于放射免疫分析法的检测限)。服用T3 4周后,血清平均值为:T4,39±6;反T3,0.11±0.01;T3,5.31±0.39;T3S,0.10±0.01纳摩尔/升。服用PTU 2天后,血清T4平均值升至48±7(P<0.005),反T3升至0.20±0.03(P<0.025),T3S升至0.13±0.01纳摩尔/升(P = 无显著性差异),但血清T3未改变(4.91±0.35纳摩尔/升)。IOP的作用更明显;服用3天后,血清T4平均值为49±8(P<0.001),反T3为0.48±0.09(P<0.005),T3S为0.29±0.04纳摩尔/升(P<0.005),血清T3降至3.95±0.25纳摩尔/升(P<0.005)。PTU使T3S/T3比值从0.018±0.003增至0.024±0.004(P≤无显著性差异),IOP使其增至0.055±0.007(P<0.005)。总之,1)正常受试者血清T3S实际上无法检测到(低于0.1纳摩尔/升);2)服用T3的人类中可检测到低血清T3S浓度;3)用PTU尤其是IOP抑制I型脱碘酶活性可使T3治疗受试者的血清T3S升高;4)与先前对大鼠血清T3S/T3比值的估计相比,人类中该比值较低可能表明硫酸化不是人类T3代谢的重要机制和/或血浆T3和T3S在人类和大鼠中的动力学不同。