Jennings A S, Ferguson D C, Utiger R D
J Clin Invest. 1979 Dec;64(6):1614-23. doi: 10.1172/JCI109623.
This study was undertaken to determine what factors control the conversion of thyroxine (T(4)) to triiodothyronine (T(3)) in rat liver under conditions approximating those found in vivo. Conversion of T(4) to T(3) was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T(4) from perfusion medium and converted it to T(3). Production of T(3) by the perfused liver was a function of the size of the liver, the uptake of T(4) by the liver, and the presence of T(4)-5'-deiodinase activity. Production of T(3) was increased by increasing the uptake of T(4) by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T(4) concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T(4) to T(3). The liver had a large capacity for extracting T(4) and for T(4)-5'-deiodination to T(3), which was not saturated at a T(4) concentration of 60 mug/dl. Production of T(3) was decreased by inhibiting hepatic T(4)-5'-deiodinase with propylthiouracil, which decreased T(3) production by decreasing the conversion of T(4) to T(3). Propylthiouracil did not alter hepatic T(4) uptake. Fasting resulted in a progressive decrease in hepatic T(4) uptake to 42% of control levels by the 3rd d of fasting; this was accompanied by a proportionate decrease in T(3) production. The rate of conversion of T(4) to T(3) did not change during fasting. When T(4) uptake in 2-d-fasted rat livers was raised to levels found in fed rats by increasing the perfusate T(4) concentration from 10 to 30 mug/dl, T(3) production returned to normal. Again, no change in the rate of conversion of T(4) to T(3) was observed. These results indicate that the decreased hepatic T(3) production during fasting primarily results from decreased hepatic uptake of T(4), rather than from changes in T(4)-5'-deiodinase activity. Thus, these studies have delineated a new mechanism that functions independently of enzyme quantity or activity whereby production of T(3) from T(4) is regulated.
本研究旨在确定在接近体内情况的条件下，哪些因素控制大鼠肝脏中甲状腺素（T4）向三碘甲状腺原氨酸（T3）的转化。在离体灌注大鼠肝脏中研究了T4向T3的转化，该制备方法能维持细胞和结构完整性，且能执行肝脏的大部分生理功能。灌注肝脏能轻易地从灌注培养基中摄取T4并将其转化为T3。灌注肝脏产生T3的量是肝脏大小、肝脏对T4的摄取以及T4 - 5'-脱碘酶活性的函数。通过增加肝脏对T4的摄取可提高T3的产生量，这可通过增大肝脏大小、提高灌注液中T4浓度或降低灌注液白蛋白浓度来实现。这些变化并未改变T4向T3的转化。肝脏对T4的摄取以及将T4 - 5'-脱碘化为T3的能力很强，在T4浓度为60μg/dl时未达到饱和。用丙硫氧嘧啶抑制肝脏T4 - 5'-脱碘酶可降低T3的产生，这是通过减少T4向T3的转化来实现的。丙硫氧嘧啶并未改变肝脏对T4的摄取。禁食导致肝脏对T4的摄取逐渐减少，到禁食第3天时降至对照水平的42%；同时T3的产生也相应减少。禁食期间T4向T3的转化速率未改变。当通过将灌注液中T4浓度从10μg/dl提高到30μg/dl，使禁食2天的大鼠肝脏对T4的摄取量提高到喂食大鼠的水平时，T3的产生恢复正常。同样，未观察到T4向T3的转化速率有变化。这些结果表明，禁食期间肝脏T3产生量的减少主要是由于肝脏对T4的摄取减少，而非T4 - 5'-脱碘酶活性的变化。因此，这些研究阐明了一种独立于酶量或活性起作用的新机制，通过该机制可调节T4生成T3的过程。
