title: The influence of steroid hormone metabolites on the in vitro development of erythroid colonies derived from human bone marrow.
abstract: Certain C19 and C21 steroid metabolites, when incubated with normal human bone marrow cells in culture, increased the number of erythroid colonies in the presence of erythropoietin. Among a number of pairs of C5 epimeric steroids tested, most 5beta (A:B cis) steroids stimulated the growth of both early erythroid progenitor cells (BFU-E) and late erythroid progenitor cells (CFU-E), whereas only a few 5alpha-(A:B trans) steroids stimulated the growth of CFU-E. No 5alpha-compounds of six pairs of steroids studied were found to stimulate BFU-E formation. This structure-activity relationship conforms with that previously observed in studies of steroid induction of ALA-synthase in avian embryo liver cells and hemoglobin synthesis in the cultured avian blastoderm. When human bone marrow cells were preincubated with the steroids for 2 d, followed by incubation with erythropoietin, only the 5 beta-compounds stimulated the growth of BFU-E. Similarly, when addition of steroids was delayed in relation to erythropoietin in the culture, only the 5 beta-derivative of a pair of C5 epimeric compounds displayed an enhancing effect on the growth of BFU-E. This effect required that the steroid addition be made no later than 48 h after initiation of the culture. These data demonstrate that certain natural steroid metabolites significantly stimulate erythropoiesis in normal human bone marrow cells in culture. They also indicate that 5 beta-compounds are more stimulatory than their 5 alpha-epimers, and they suggest that these 5 beta-steroids act preferentially on very primitive erythroid progenitor cells, probably on BFU-E.
mesh_terms: D000731:Androstanes / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002777:Cholestanols / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D011278:Pregnanes / Q000494:pharmacology*; D013261:Sterols / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000731:Androstanes; D002777:Cholestanols; D011278:Pregnanes; D013261:Sterols; D004921:Erythropoietin