The influence of steroids on erythropoiesis in mouse fetal liver cell cultures: relevance of cell cycle state.

It has been shown that erythropoietin-mediated stimulation of heme synthesis in mouse fetal liver cells in vitro is correlated with hydroxyurea sensitivity. Assuming that OHU is specifically cytotoxic for cells in DNA synthesis this suggests that erythropoietin sensitivity may be related to this phase of the cell cycle. The direct effects of 19-nortestosterone and 3beta-hydroxy-5beta-pregnan-20-one on heme synthesis correlated with the capacity of these steroids to initiate DNA synthesis. It is suggested that the ability of these steroids to increase the proportion of cells in the Ep-sensitive phase of the cell cycle is probably the mechanism responsible for the erythropoietic effects of these agents. 17beta-hydroxy-5alpha-androstan-3-one appears to have a different mode of action since it has only minimal effects on heme synthesis and did not increase hydroxyurea sensitivity.