Hays Marguerite T
Cooperative Studies, VA Palo Alto Health Care System, Palo Alto, California, USA.
Thyroid. 2009 Sep;19(9):1001-4. doi: 10.1089/thy.2008.0375.
Rapid deconjugation of administered thyroxine glucuronide (T4G) to thyroxine (T4) has been observed in human subjects. The goal of this study was to characterize, in the rat, the location and kinetics of this deconjugation process and to identify whether early conjugation of T4 to T4G occurs in the liver.
Normal male rats received intraportal radiolabeled T4 and T4G. Tissues were assayed 1 to 15 minutes after the injection.
After T4G injection, assay of the kidneys, and to a lesser extent assay of the liver and plasma, showed presence of considerable T4, the result of deconjugation. In the kidneys, 79 +/- 12% (mean +/- SD%) of total (T4 + T4G) was in T4 form. In the liver and plasma, T4 was 10 +/- 9% and 6 +/- 5%, respectively, of the total (T4 + T4G). No significant conjugation of T4 occurred in any of the tissues assayed during this short time period. Secretion in the bile of administered T4G as T4G increased with time.
These data, together with the previous observations in human subjects, suggest that T4G, with its greater tissue distribution, may serve as a medium for transfer of T4 into tissues not subject to direct transfer of T4 from the circulation. Hence, the true volume of distribution of T4 is postulated to be greater than that measured by tracer studies of T4 distribution.
在人体受试者中已观察到给予的甲状腺素葡萄糖醛酸苷(T4G)迅速脱结合为甲状腺素(T4)。本研究的目的是在大鼠中表征这种脱结合过程的位置和动力学,并确定T4在肝脏中是否会早期结合为T4G。
正常雄性大鼠经门静脉注射放射性标记的T4和T4G。注射后1至15分钟对组织进行检测。
注射T4G后,对肾脏的检测以及对肝脏和血浆程度较轻的检测显示存在大量T4,这是脱结合的结果。在肾脏中,总(T4 + T4G)的79±12%(平均值±标准差%)为T4形式。在肝脏和血浆中,T4分别占总(T4 + T4G)的10±9%和6±5%。在这段短时间内,所检测的任何组织中均未发生T4的显著结合。给予的T4G以T4G形式分泌到胆汁中的量随时间增加。
这些数据,连同先前在人体受试者中的观察结果,表明T4G具有更广泛的组织分布,可能作为T4转移到无法从循环中直接转移T4的组织中的一种介质。因此,推测T4的真正分布容积大于通过T4分布示踪研究测量的结果。