Comprehensive kinetics of triiodothyronine production, distribution, and metabolism in blood and tissue pools of the rat using optimized blood-sampling protocols

Abstract

We have determined estimates for 24 physiological parameters of production, interpool transport, distribution, and metabolism of T3 in the major T3 pools of the unanesthetized male Sprague-Dawley rat, from blood-borne data and a comprehensive model and analysis of this system. Most of these indices have previously been unavailable. Whereas only 3% (2 ng/100 g BW) of the total body T3 pool (74 ng/100 g BW) is in plasma, the composite of slowly equilibrating (slow) tissue pools (e.g. muscle, skin, and brain) appears to contain most of the T3, 76% (57 ng/100 g BW) of the total. The composite of rapidly equilibrating (fast) tissue pools (e.g. liver and kidney) contains the remaining 19% (16 ng/100 g BW). The total body T3 production rate is 0.12 ng/100 g BW . min, and we estimate that about half of this emanates directly from T4 in the slow pools, whereas the remainder is derived from both thyroidal secretion and T4 to T3 conversion in the fast pools. Our results also indicate that T3 molecules spend an average of only 0.5 min in transit each time through plasma, whereas the single pass mean transit times in fast and slow tissue pools (the times available for hormone action) are 10 times and 200 times greater. In contrast, the mean residence time for T3 in the entire system is greater than 12 h despite the extremely rapid early disappearance of injected T3 from plasma. To obtain the required accuracy, we used a novel optimization approach for choosing blood-sampling schedules (1, 4, 44, 202, and 600 min), a remarkably small number of sample times, and each was adjustable by about +/- 20% without effect on optimized parameter accuracies.