Earlier studies from this and other laboratories demonstrated that certain naturally occurring steroid metabolites, formerly considered to be physiologically inactive end products of hormone metabolism, strongly stimulate porphyrin and &aminolevulinic acid synthase (ALA-S) 1 formation in cultured chick embryo liver eeUs (1, 2) as well as in vivo in the liver of the chick embryo (3). Steroid metabolites with a 5fl-structure (A:B cis) were more potent in this respect than their 5a-epimers or their parent compounds. 5fl-steroids which induce porphyrin synthesis in chick embryo liver cells have also been shown to induce the early synthesis of hemoglobin in the erythroblasts of the chick blastoderm (4) and a 5fl-steroid receptor in this primitive avian tissue has been identified (5).These steroid metabolites have been also reported to stimulate erythropoiesis in vivo in mice. For example, Gorshein and Gardner (6) described enhanced erythropoiesis in exhypoxic polycythemic mice after 5fl-steroid administration as determined by 59Fe incorporation into peripheral erythrocytes. Gordon et al. (7) reported similar results using both normal and poiycythemic mice; in addition, their study showed that an antibody preparation against erythropoietin abolished the effects of testosterone, but not those of 5fl-steroids. These data thus suggested that 5fl-steroids can have effects on erythropoiesis that are independent of the action of erythropoietin. Besa et al. (8) later demonstrated that the 5fl-compound, etiocholanolone (5fl-androstan-3a-ol-17-one), increased erythrocyte mass in squirrel monkeys, confirming that such steroid metabolites may stimulate erythropoiesis not only in the erythroid tissues of birds, rodents, but also in vivo in primates. 5fl-steroids have also been demonstrated to increase both heme and globin synthesis in suspension cultures of human bone marrow cells (9, 10).The development of newer methodology for the study of hematopoietic stem cells in culture (11-13) made it possible to examine the mechanism and site of action of erythropoietin and steroids on the development of erythroid colonies in semisolid media (14). Using rat bone marrow cells, Singer et al. (15) reported that certain steroids enhanced erythroid colony growth in vitro and suggested that etiocholanolone, a prototype 5fl-steroid, may act on early erythroid progenitor cells (16).

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