Interactions of insulin, insulinlike growth factor II, and platelet-derived growth factor in erythropoietic culture

To examine the influence of insulin and insulinlike growth factor (IGF) on erythropoiesis, we tested their effects in human bone marrow cultures prepared with biochemically defined medium or a platelet-poor plasma-derived serum (PDS) that was depleted of hormones by adsorption to activated charcoal. Erythroid colony formation was enhanced two- to threefold by 10 ng/ml of electrophoretically pure IGF-II and 100 ng/ml of highly purified insulin (P less than 0.05). Dose-response curves for IGF-II were parallel to and shifted by one to two orders of magnitude to the left relative to those for insulin. When added together to culture, IGF-II and insulin expressed additive activities. In contrast, their activities were synergistic with those of erythropoietin and burst-promoting activity. The erythropoietic actions of IGF-II and insulin were similar in PDS and whole blood serum (WBS) containing cultures. Furthermore, when added to cultures with electrophoretically pure platelet-derived growth factor, their respective activities were synergistic. We conclude that insulin and IGF-II potentiate human marrow erythropoiesis in vitro. Their activities appear to be mediated by a similar receptor or postreceptor system.