Studies on the Control of Hemoglobin Synthesis: The in vitro Stimulating Effect of a 511.H Steroid Metabolite on Heme Formation in Human Bone Marrow Cells

T HE EFFECT OF ANDROGENIC STEROIDS on hemoglobin levels has usually been ascribed to an indirect effect of these hormones, possibly secondary to an effect upon erythropoietin production or activation.1’2 Earlier studies of the in vitro effect of androgens on bone marrow cells provided conflicting evidence for a direct effect upon erythroid cell proliferation or hemoglobin synthesis. Reisner3 presented evidence for an in vitro effect upon iron incorporation by canine bone marrow cells whereas other workers were unable to confirm these results.4 In earlier studies, we could not document an in vitro effect of testosterone on hemoglobin synthesis, nucleic acid synthesis, or erythroid cell proliferation. Recently Granick and Kappas and their coworkers57 have published a series of papers in which they report a potent stimulation of heme synthesis in embryonic chick liver and erythropoietic tissues using certain metabolic derivatives of androgenic steroids. We have now demonstrated a similar in vitro effect of 5 fl-H metabolites of testosterone in adult human erythropoietic tissue. These data add support to the concept that androgenic hormones or their metabolic products may act directly upon human red cell precursors.