The influence of tryptophan on hepatic polyribosomes and protein synthesis in fasted mice

Abstract

This study evaluated whether selected hormones, 3,5,3′-triiodothyronine (T3), hydrocortisone (HC), or insulin, would influence the binding ofl-tryptophan to rat hepatic nuclei or nuclear envelopes. The first two hormones have nuclear receptors that belong to the same superfamily, while insulin belongs to a different unrelated superfamily of receptors. Previous reports have indicated that the binding ofl-tryptophan to hepatic nuclear proteins was saturable, stereospecific, and of high affinity. Also, previous studies showed that administration ofl-tryptophan rapidly stimulated hepatic protein synthesis. In this study, we investigated whether each hormone alone or together with unlabeled tryptophan would influence tryptophan binding to rat hepatic nuclei or nuclear envelopes as assayed by in vitrol-5-3H-tryptophan binding. Our results indicate that T3 10−14 to 10−10 mol/L appreciably inhibited in vitro3H-tryptophan binding to hepatic nuclei and T3 10−16 to 10−4 mol/L appreciably ameliorated the inhibitory effect of unlabeled tryptophan (10−4 mol/L) on in vitro3H-tryptophan binding. In vivo administration (1 hour) of tryptophan alone stimulated hepatic protein synthesis, but addition of T3 negated such stimulation. Addition of HC 10−12 to 10−4 mol/L had no effect and addition of insulin 10−16 to 10−4 mol/L had only a small inhibitory effect on in vitro3H-tryptophan binding to rat hepatic nuclei, but each (10−12 to 10−4 mol/L), when added to unlabeled tryptophan (10−4 mol/L), diminished the inhibitory binding effect of unlabeled tryptophan alone. Our study indicates that T3 competes with tryptophan for hepatic nuclear tryptophan binding, and it also appears to negate tryptophan's stimulatory effect on hepatic protein synthesis.