INTERACTIONS BETWEEN THYROID-HORMONE AND TRYPTOPHAN TRANSPORT IN RAT-LIVER ARE MODULATED BY THYROID STATUS

We have identified both N-ethylmaleimide (NEM)-resistant (system T) an d NEM-sensitive (system L-1) L-[H-3]tryptophan transporters in sinusoi dal membrane vesicles (SMVs) from euthyroid, hypothyroid (propylthiour acil-treated), and hyperthyroid [L-3,5,3'-triiodothyronine (L-T-3)-inj ected] rats. L-[I-125]T-3 associates with SMVs largely by surface bind ing. Kinetic characteristics of tryptophan uptake and T-3 binding (tra nsporter or receptor abundance and substrate affinity) are not signifi cantly affected by thyroid status. T-3 and thyroxine (T-4) inhibit NEM -resistant tryptophan uptake in SMVs to an extent dependent on the thy roid status of the donor rat, increasing in the order hypothyroid < eu thyroid < hyperthyroid; the inhibitor constant for this inhibition (0. 3 mu M T-3) is equal to the dissociation constant for T-3 binding. Bot h T-3 binding and T-3 inhibition of tryptophan transport in SMVs are m arkedly reduced by treatments (Triton X-100 or trypsin) that do not si gnificantly affect vesicle integrity or transport of tryptophan and gl ucose. T-3 and/or T-4 transport at the liver-plasma interface may be f acilitated by direct interactions between hormone receptors and system T transporter proteins. Modulation of such interactions may be import ant for control of hepatic T-4 and/or T-3 turnover and aromatic amino acid metabolism during altered thyroid status.