Effect of Thyroid Hormone on Polypeptide Chain Assembly Kinetics in Liver Protein Synthesis in Vivo

Abstract

Abstract The time constant for assembly and release of polypeptide chains in the process of protein synthesis in rat liver in vivo has been determined by a new technique which is independent of most sources of variation and error in amino acid incorporation experiments. In this method the ratio of incorporation of 14C-amino acids into completed soluble proteins to that in total protein (including ribosome-bound chains) is measured as a function of short incubation periods (15 to 105 s) after hepatic portal vein injection to obtain tc, the average polypeptide chain assembly time. For normal male Long-Evans rats, ages 2 to 2½ months, tc in liver in vivo is 1.16 ± 0.16 min. Induction of hyperthyroidism by three injections of triiodothyronine (40 µg/100 g body weight) over 72 hours led to a value of tc = 0.92 ± 0.08 min, representing a 27% increase in synthetic rate. Surgically thyroidectomized rats showed a markedly longer time for polypeptide chain assembly, tc = 1.92 ± 0.22 min, corresponding to a 39% depression in protein synthetic output compared with sham-operated and normal controls of the same age. Almost complete recovery of protein synthetic rate in thyroidectomized rats was achieved by replacement doses of triiodothyronine (20 µg/100 g body weight) given daily for 2 days prior to assay. The results are discussed in relation to the mechanism of control of the protein synthetic pathway, the anabolic action of the thyroid hormones, and other methodology which has been used in attempts to estimate protein synthetic capacity.