GLUCOCORTICOID-MEDIATED INHIBITION OF ERYTHROID COLONY FORMATION BY MOUSE BONE-MARROW CELLS

The ability of bone marrow cells, obtained from mice pretreated with the synthetic glucocorticoid dexamethasone, to form erythroid colonies in vitro was studied. These bone marrow cells formed a reduced number of erythroid colonies in vitro in response to Epo [erythropoietin]. This effect was evident after single injection (1 mg, i.p.) of dexamethasone (46% of control values) and was at a maximum after 2-4 consecutive treatments (12-17% of control values). To eliminate the influence of influx or efflux of cells to or from the bone marrow, the effect of dexamethasone on erythroid colony formation in vitro was examined. In these experiments, bone marrow cells cultured in the presence of Epo (25 mU [units]) and dexamethasone (2 .times. 10-6 M to 2 .times. 10-8 M) formed fewer erythroid colonies than cells cultured in the presence of Epo alone. The ability of the antiglucocorticoid, 17.alpha.-methyltestosterone (2 .times. 10-7 M) to reverse this dexamethasone-mediated inhibition of erythroid colony formation suggested that this phenomenon was mediated through a glucocorticoid receptor. Dexamethasone, in vivo or in vitro, decreases the number and/or functional capacity of adult murine bone marrow cells capable of forming erythroid colonies in vitro in response to Epo, although the precise mechanism of this inhibition remains to be established.