The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro

Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper b alance between progenitor proliferation and differentiation, In avian eryth roid progenitors, steroid hormones cooperate with tyrosine kinase receptors to induce renewal of erythroid progenitors. We examined the role of cortic osteroids in the in vitro expansion of primary human erythroid cells in liq uid cultures and colony assays. Dexamethasone (Dex), a synthetic glucocorti coid hormone, cooperated with Epo and stem cell factor to induce erythroid progenitors to undergo 15 to 22 cell divisions, corresponding to a 10(5)- t o 10(6)-fold amplification of erythroid cells, Dex acted directly on erythr oid progenitors and maintained the colony-forming capacity of the progenito r cells expanded in liquid cultures. The hormone delayed terminal different iation into erythrocytes, which was assayed by morphology, hemoglobin accum ulation, and the expression of genes characteristic for immature cells. Sus tained proliferation of erythroid progenitors could be induced equally well from purified erythroid burst-forming units (BFU-E), from CD34(+) blast ce lls, and from bone marrow depleted from CD34(+) cells. (C) 1999 by The Amer ican Society of Hematology.