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 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.
Institute of Hematology, Erasmus University, Rotterdam, The Netherlands. vonlindern@hema.fgg.eur.nl
M
M
von Lindern
W
W
Zauner
G
G
Mellitzer
P
P
Steinlein
G
G
Fritsch
K
K
Huber
B
B
Löwenberg
H
H
Beug
D000328:Adult; D000367:Age Factors; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D009928:Organ Specificity; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology*; D017467:Receptors, Erythropoietin / Q000187:drug effects / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D017467:Receptors, Erythropoietin; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D003907:Dexamethasone; D019009:Proto-Oncogene Proteins c-kit