ENHANCEMENT OF HEME AND GLOBIN SYNTHESIS IN CULTURED HUMAN MARROW BY CERTAIN 5ß-H STEROID METABOLITES

Abstract

These studies demonstrate that certain sex steroid metabolites are capable of significantly stimulating the synthesis of both heme and globin in cultured human bone marrow cells. These compounds, which are maximally effective at a concentration of 3 x 10–8 M, are steroids of the C19 and C21 neutral type; share a common 5ß-H (A:B cis) configuration; and are derived from the in vivo biotransformation of testosterone or progesterone, or their intermediates, in man. Since these steroid metabolites have been shown to be capable in other systems of inducing the synthesis of δ-aminolevulinic acid synthetase, the limiting enzyme in the heme biosynthetic pathway, it is hypothesized that their action on human erythroid precursor cells is directed similarly at this enzymatic step leading thereby to increased heme production with consequent stimulation of globin synthesis. This steroid action is independent of erythropoietin, and since these compounds are effective at extremely low concentrations, it is suggested that they may play a physiologic role in the regulation of human erythropoiesis.