ADAPTIVE-CHANGES IN TRANSMEMBRANE TRANSPORT AND METABOLISM OF TRIIODOTHYRONINE IN PERFUSED LIVERS OF FED AND FASTED HYPOTHYROID AND HYPERTHYROID RATS

The transport and subsequent metabolism of triiodothyronine (T-3) were studied in isolated perfused livers of euthyroid, hypothyroid, and hy perthyroid rats, both fed and 48-hour-fasted. T-3 kinetics (transport and metabolism) during perfusion were evaluated by a two-pool model, w hereas the metabolism of T-3 was also investigated by determination of T-3 breakdown products by chromatography of medium and bile. For comp arison of groups, metabolism was corrected for differences in transpor t. Transport parameters in fed hypothyroid livers were not significant ly changed as compared with euthyroid livers, whereas metabolism was d ecreased. In fed hyperthyroid livers, fractional transfer rate constan ts for influx (k(21)) and efflux (k(12)) were decreased and metabolism , corrected for differences in intracellular mass transfer, was increa sed. Furthermore, for transport in hyperthyroid livers it was shown th at only total mass transfer (TMT) into the metabolizing liver compartm ent (not into the nonmetabolizing liver compartment) was decreased. Tr ansport and metabolic parameters in fasted hypothyroid livers were dec reased as compared with euthyroid fed livers. In fasted hyperthyroid l ivers, transport and metabolism were not significantly different as co mpared with that in euthyroid fed livers, so transport was increased v ersus hyperthyroid fed livers. It appeared therefore that fasting norm alized the effects of hyperthyroidism on both the transport and metabo lic processes of T-3 in the liver. The present study demonstrates norm al transport and decreased metabolism in livers of hypothyroid fed rat s and decreased transport and increased metabolism in livers of hypert hyroid fed rats. In livers of hypothyroid fasted rats transport and me tabolism were decreased, whereas in livers of hyperthyroid fasted rats transport and metabolism were not significantly different from that i n euthyroid fed livers. These changes might favor tissue euthyroidism despite the altered thyroid and nutritional state, and can therefore b e seen as adaptation mechanisms to these altered states at the tissue level. Copyright (C) 1994 by W.B. Saunders Company