The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro
January 1999
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Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors to induce renewal of erythroid progenitors. We examined the role of corticosteroids in the in vitro expansion of primary human erythroid cells in liquid cultures and colony assays. Dexamethasone (Dex), a synthetic glucocorticoid hormone, cooperated with Epo and stem cell factor to induce erythroid progenitors to undergo 15 to 22 cell divisions, corresponding to a 10(5)- to 10(6)-fold amplification of erythroid cells. Dex acted directly on erythroid progenitors and maintained the colony-forming capacity of the progenitor cells expanded in liquid cultures. The hormone delayed terminal differentiation into erythrocytes, which was assayed by morphology, hemoglobin accumulation, and the expression of genes characteristic for immature cells. Sustained proliferation of erythroid progenitors could be induced equally well from purified erythroid burst-forming units (BFU-E), from CD34(+) blast cells, and from bone marrow depleted from CD34(+) cells.
- Comparative Study
- Adult
- Humans
- Research Support, Non-U.S. Gov't
- Age Factors
- Infant, Newborn
- Cells, Cultured
- Cell Division/drug effects
- Drug Synergism
- Organ Specificity
- Recombinant Proteins/pharmacology
- Antigens, CD34/analysis
- Blood Cells/cytology/drug effects
- Bone Marrow Cells/cytology/drug effects
- Cell Differentiation/drug effects
- Dexamethasone/pharmacology
- Antigens, Differentiation/analysis
- Erythroid Progenitor Cells/*cytology/drug effects/metabolism
- Erythropoiesis/drug effects/*physiology
- Fetal Blood/cytology
- Proto-Oncogene Proteins c-kit/*physiology
- Receptors, Erythropoietin/drug effects/*physiology
- Receptors, Glucocorticoid/drug effects/*physiology
- Stem Cell Factor/pharmacology
- Erythropoietin/pharmacology
- erythroid
- erythroid progenitors
- culture
- progenitors
- cd 34 cells
- receptor
- proliferation
- differentiation
- factor
- blood
- number
- c-kit
- medium
- marrow
- colony
- cell numbers
- bone marrow
- beug h
- cord blood
- bone marrow cells