Hydrocortisone-induced inhibition of protein synthesis and uridine incorporation in isolated bone cells in vitro.

Abstract

Hydrocortisone (10-5 to 10~8 M) inhibited the incorporation of proline Cl4 into collagen and non-collagen protein by bone cells in primary culture. Decreased protein labeling was accompanied by an accumulation of radioactive free proline in the tissue, suggesting a block in the utilization of intracellular amino acids for protein sy thesis. No marked increase in the rate of protein breakdown could be demonstrated. Hydrocortisone also inhibited the uptake of uridine-2-C14 into the tissue pools of free uridine and uridine nucleotides, and its incorporation into RNA. Decreased pool and RNA labeling were dissociated with actinomycin D and at high extracellular uridine concentrations. There was a 5-10% decrease in total tissue RNA content, which, with decreased radioactivity, suggests an inhibition of RNA synthesis. An increase in RNA breakdown, too small to be detected with pulse-chase experiments, cannot be excluded. These changes were not accompanied by significant alterations in thymidlne incorporation or in the amount of DNA per culture. The slow and simultaneous appearance of hydrocortisone-induced changes in protein and RNA metabolism indicates that they may both be caused by a separate and earlier effect on bone cell metabolism.