T-4 UPTAKE INTO THE PERFUSED-RAT-LIVER AND LIVER T-4 UPTAKE IN HUMANSARE INHIBITED BY FRUCTOSE

Recently, we described a two-pool model for 3,5,3'-triiodothyronine up take and metabolism in the isolated perfused rat Liver. Here, we appli ed this model to investigate transmembrane thyroxine (T-4)transport an d its possible ATP dependence in vivo. These studies are performed in perfused rat livers during perfusion with or without fructose in the m edium, as it has been shown that intracellular ATP is decreased after fructose loading. Furthermore, we studied serum T-4 tracer disappearan ce curves in four human subjects before and after intravenous fructose loading. In the perfused rat liver, we found a decrease in liver ATP concentration and a decrease in medium T-4 disappearance and T-4 uptak e in the liver pool after fructose. Furthermore, it was shown that, wh en corrected for differences in the medium free hormone concentration, only transport to the metabolizing liver pool was decreased after fru ctose perfusion, whereas uptake in the nonmetabolizing pool was unaffe cted. Disposal, corrected for differences in transport into the metabo lizing pool, was also not affected after fructose. In the human studie s, intravenous fructose administration induced a rise in serum lactic acid and uric acid, indicating a decrease in liver ATP. This was obser ved concomitant with a decrease in serum tracer T-4 disappearance duri ng the first 3 h after fructose administration. These results suggest ATP dependence of transport of iodothyronines into the liver in vivo a nd show that, in the rat liver and in humans, uptake of T-4 may be reg ulated by intracellular energy stores; in this way the tissue uptake p rocess may affect intracellular metabolism and bioavailability of thyr oid hormone.