Time Course of Early Events in the Action of Glucocorticoids on Rat Thymus Cells in Vitro: SYNTHESIS AND TURNOVER OF A HYPOTHETICAL CORTISOL-INDUCED PROTEIN INHIBITOR OF GLUCOSE METABOLISM AND OF A PRESUMED RIBONUCLEIC ACID

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Abstract Previous work has shown that physiological amounts of cortisol added to rat thymus cells in vitro begin to inhibit glucose transport (as measured by the accumulation of glucose 6-phosphate during a 5-min glucose pulse) by 15 to 20 min; the effect of cortisol is blocked by actinomycin D present from 0 to 5 min, suggesting a rapid stimulation by cortisol of RNA synthesis. It is now shown that during the period from 15 to 30 min, but not prior to 15 min, the hormone effect is blocked by cycloheximide or puromycin. The coincidence in time of sensitivity to these inhibitors of protein synthesis with the development of inhibition of glucose transport, together with our earlier results, has led us to postulate that the hormone effect is expressed through induction of a protein that rapidly inhibits glucose transport. The preceding RNA-synthetic step possibly represents synthesis of mRNA for this protein. The previously demonstrated temperature-sensitive step is shown to lie between the RNA- and protein-synthetic steps. It perhaps corresponds to transfer of mRNA from nucleus to cytoplasm. Decay rates of the hypothetical cortisol-induced RNA and protein have been measured following removal of hormone from specific binding sites or addition of inhibitors of RNA or protein synthesis. The protein appears to have a life span of not more than 2 hours at 37°, while the RNA has a life span of less than 40 min.