Role of Protein Synthesis in the Inhibitory Action of Adrenal Steroid Hormones on Amino Acid Transport by Muscle1

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Abstract
Adrenal steroid hormones added in vitro inhibit the accumulation of amino acids by isolated rat diaphragm, but inhibition appears only some hours after the presumed interaction of the hormone with the tissue. Since it is known that the administration of corticosteroids to rats impairs protein synthesis in muscle, experiments were performed to explore the possibility that the delay in their effect on amino acid uptake might be due to the inhibition of protein synthesis. Preincubation of intact diaphragms of adrenalectomized rats with corticosterone (10-5 [image]) for 2-3 hr. did suppress the subsequent incorporation of L-metEionine-C14 into total diaphragm protein, although preincubation for 1 hr. had no effect. This time course of inhibition was similar to that observed when AIB [[alpha]-aminoisobutyric acid] accumulation was measured. Preincubation of diaphragms with puromycin (0.37 m[image]) or actinomycin D (5 [mu]g/ml) inhibited the subsequent accumulation of AIB by the cells, and the time course of inhibition was comparable to that produced by corticosterone. When diaphragms were preincubated for 3 hr. in medium containing both puromycin and corticosterone, AIB accumulation was inhibited, but to an extent equal to that produced by either substance alone. However, accumulation of AIB could be inhibited further by the addition of DNP (10-4 [image]) [dinitrophenol] to the medium. AIB accumulation was also suppressed in diaphragms isolated from rats that had received injections of the amino acid analogue, DL-ethionine. The agreement of these findings with the idea that corticosteroids inhibit muscle amino acid transport through their inhibitory action on protein synthesis is discussed.