Glucocorticoids Inhibit Erythroid Colony Formation by Murine Fetal Liver Erythroid Progenitor Cellsin Vitro*

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Abstract
Dexamethasone (10-6-10-8 M) significantly decreased the number of erythroid colonies which formed when 15-day-old CD-1 murine fetal liver erythroid progenitor cells were cultured in plasma clots in the absence of exogenous erythropoietin. Lower concentrations of dexamethasone did not affect the number of endogenous erythroid colonies which formed in these cultures. Dexamethasone (10-6-10-9 M) also significantly reduced the number of erythroid colonies which formed in the presence of exogenous erythropoietin; this inhibitory affect was evident regardless of the concentration of exogenous erythropoietin in the cultures. Similar results were obtained with fetal liver erythroid progenitor cells from 16- or 17-day-old fetuses; no endogenous erythroid colonies formed from cultured 17-day-old fetal liver cells. Other glucocorticoids, including prednisone, prednisolone, corticosterone, cortisol, 9α-fluorocortisol, and triamcinolone acetonide, also inhibited the formation of endogenous erythroid colonies and erythroid colonies, which form in response to exogenous erythropoietin. An antiglucocorticoid (17α-methyltestosterone), at a concentration which neither enhanced nor suppressed erythroid colony formation, was able to reverse partially (68%) the dexamethasonemediated inhibition of erythroid colony formation, suggesting that glucocorticoid receptor proteins are involved in the glucocorticoid-mediated inhibition of erythroid colony growth. An analysis of the individual clones of erythroid cells produced in the presence of dexamethasone was consistent with the hypothesis that glucocorticoids suppress erythroid colony growth largely,by delaying the entry of erythroid colony-forming cells into the S phase of the cell cycle. These data provide a mechanism for, the suppressive influence of glucocorticoids on the hepatic stage of fetal erythropoiesis which occurs in vivo, and show that this inhibitory effect can be simulated in vitro.