Exchange of triiodothyronine derived from thyroxine with circulating triiodothyronine as studied in the rat

At present it is widely assumed that T3 derived from T4 is rapidly and totally exchangeable within the volume of distribution of T3 secreted by the thyroid into the bloodstream. This concept is implied when conclusions are drawn from comparisons between a biological effect in a responsive tissue and circulating T3 and T4 levels. Such conclusions are often in conflict with those derived by comparing the biological effect with the concentrations of T3 and T4 in the responsive tissue itself. Thus, it appeared important to test the above assumption directly. Thyroidectomized rats have been treated for 4-4 1/2 days with a mixture of 131I labelled T4 (131T4) and 125I labelled T3 (125T3), which was either injected twice daily or administered by continuous i.v. infusion. The rats were bled, perfused, and their plasma and tissues submitted to extraction and paper chromatography. If the tested assumption were correct, the ratio between the T3 derived from T4 and the T3 injected as such (namely, the 131T3/125T3 ratio) should be the same in plasma, liver, kidney, heart, muscle, etc. It was evident that the 131T3/125T3 ratio was not the same for different tissues. The differences were not merely due to artefactual deiodinations. The presence of small amounts of 131I and 125I containing compounds in the T3 spot was considered as highly unlikely, though not totally excluded. The data thus suggest that T3 derived from T4 and the injected (or thyroidally secreted) T3 might not be totally exchangeable within an observation period which is considerably longer than the one for which complete equilibrium was previously assumed. If so, changes in the size of the T4 pool, or in the rate of T4 conversion to T3, might affect the concentration of T3 in a given tissue to an extent not disclosed from the circulating T3 levels alone. Several possible consequences of the present findings are discussed.