INHIBITION BY DEXAMETHASONE OF COMMITMENT TO ERYTHROID-DIFFERENTIATION IN MURINE ERYTHROLEUKEMIA-CELLS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (10) , 3849-3855
Abstract
The inhibition of erythroid differentiation of murine erythroleukemia by cells by dexamethasone (DEX) was investigated on a clonal basis [as a model for corticosteroid effects on cellular differentiation]. At concentrations which had no detectable effect on cell proliferation, DEX3 rapidly inhibited the dimethyl sulfoxide (DMSO)-induced commitent of individual murine erythroleukemia cells to the differentiation program. DEX did not prevent heme accumulation in cells already committed to the differentiation process. The rate of globin mRNA synthesis was reduced in cells treated with DMSO and DEX compared to cells treated with DMSO alone. The reduction in the rate of globin mRNA synthesis was proportional to the reduction caused by DEX in the rate of commitment. DEX inhibition in the rate of commitment and of globin mRNA synthesis of DMSO-treated cells was reversible. Upon removal of DEX, continued DMSO treatment resulted in a rapid increase in the rate of globin mRNA synthesis and the rate of commitment. The rate of globin mRNA synthesis after DEX release was proportional to the rate of commitment. DEX apparently exerts an inhibitory effect on heme and globin synthesis by blocking commitment to terminal erythroid differentiation.