Outgrowth, long-term self-renewal, and terminal maturation of human erythroid 
progenitors derived from umbilical cord blood in serum-free medium can be 
modulated by steroid hormones. Homogeneous erythroid cultures, as characterized 
by flow cytometry and dependence on a specific mixture of physiologic 
proliferation factors, were obtained within 8 days from a starting population of 
mature and immature mononuclear cells. Due to previous results in mouse and 
chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was 
not unexpected. Surprisingly, however, androgen had a positive effect on the 
sustained expansion of human female but not male erythroid progenitors. Under 
optimal conditions, sustained proliferation of erythroid progenitors resulted in 
a more than 10(9)-fold expansion within 60 days. Terminal erythroid maturation 
was significantly improved by adding human serum and thyroid hormone 
(3,5,3'-triiodothyronine [T3]) to the differentiation medium. This resulted in 
highly synchronous differentiation of the cells toward enucleated erythrocytes 
within 6 days, accompanied by massive size decrease and hemoglobin accumulation 
to levels comparable to those in peripheral blood erythrocytes. Thus, obviously, 
different ligand-activated nuclear hormone receptors massively influence the 
decision between self-renewal and terminal maturation in the human erythroid 
compartment.