Enhancement of erythropoiesis in vitro by human growth hormone is mediated by insulin-like growth factor I.

Insulin-like growth factor I (IGF-I) is the presumed paracrine or autocrine growth-promoting mediator of growth hormone in peripheral tissues. In order to evaluate the role of IGF-I as mediator of human growth hormone (hGH) in erythropoiesis, we compared the effects of both peptides upon in vitro colony formation by primitive (BFU-E) and relatively mature (CFU-E) human erythroid precursors. Biosynthetic IGF-I (2 ng/ml) and hGH (25 ng/ml) induced a significant increase in the growth of both BFU-E and CFU-E. BFU-E growth was maximally enhanced by 6 ng/ml IGF-I and by 50 ng/ml hGH, resulting in an increase in burst numbers of 62 +/- 12% and 52 +/- 12%, respectively. Maximal enhancement of CFU-E growth was detected at higher concentrations of IGF-I (20 ng/ml) and hGH (150 ng/ml), with respective increases of 121 +/- 35% and 137 +/- 18% in colony numbers. Enhancement of bone marrow and peripheral blood erythroid progenitor cell growth by hGH required the presence of monocytes and was abrogated by specific monoclonal antibodies directed against IGF-I membrane receptors. The in vitro growth-promoting effect of hGH upon human erythroid precursors thus appears to be mediated by paracrine IGF-I.