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Inhibitory Effect of Cortisol in Vitro on 2-Deoxyglucose Uptake and RNA and Protein Metabolism in Lymphosarcoma P1798¹

Department of Experimental Therapeutics, Roswell Park Memorial Institute, Buffalo, New York 14203

Exposure of cells prepared from lymphosarcoma P1798 to 1 x 10^-6 M cortisol for 3 hr produced a significant inhibition of uridine-³H incorporation into RNA (52%) and of leucine-¹⁴C into protein (44%). These effects were minimal in the cortisol-resistant P1798 cells. In the sensitive tumor, cortisol also inhibited the cellular uptake of uridine-³H into the trichloroacetic acid-soluble fraction (33%), whereas the uptake of labeled leucine was only slightly impaired (10%). Although the inhibition of leucine-¹⁴C uptake is limited, we cannot exclude this effect as a possible explanation of the inhibition of incorporation of leucine into protein. Studies utilizing -aminoisobutyric-1-¹⁴C acid indicated that the uptake of this nonmetabolizable amino acid was significantly inhibited (20%) only in cells exposed to cortisol 2 hr. When glucose was omitted from the incubation medium, the incorporation of radioactive precursors into RNA and protein was inhibited by 80 to 85%; under the same conditions, inhibition produced by cortisol was only 49 and 63%, respectively, of that observed when glucose was present in the medium. Within 1 hr, the inhibitory action of cortisol on the uptake of 2-deoxyglucose-1-¹⁴C was substantially greater than its effect on the incorporation of glycine-¹⁴C into nucleic acids and protein. Cycloheximide, at a concentration of 1.4 x 10^-5 M, inhibited 2-deoxyglucose uptake in a time-dependent fashion somewhat similar to that of cortisol, suggesting that continued protein synthesis may be required for glucose transport into P1798 cells. While the action of cortisol on glucose transport may not be the primary action of the hormone, our data suggest that this effect is important with respect to the hormone-mediated inhibition of nucleic acid and protein biosynthesis in lymphosarcoma P1798.

¹ This research was supported by NIH Grants CA-05671 and F01 GM-41,359 and Damon Runyon Grant DRG-982.

² Present address: Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tenn. 37203.

³ To whom reprint requests may be sent.

Received 8/11/71. Accepted 11/ 3/71.