Recombinant human insulin‐like growth factor 1 (rh‐IGF‐1) stimulates erythropoiesis in adult, but not in newborn mice

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Abstract
The in vivo effect of recombinant human insulin‐like growth factor (rh‐IGF‐1) upon erythropoiesis was studied in inbred BALB/C mice. Unweaned, rapidly growing 20 days old mice and adult female mice received subcutaneous rh‐IGF‐1 or control injections every 6 h for 48 h. The mice were killed either 12 or 48 h after the last injection, i.e. a study time of 60 and 96 h, respectively. Bone marrow erythroid colony forming units (CFU‐E), reticulocytes, haematocrit, serum immunoreactive erythropoietin (siEPO) and body and organ weight were measured. An additional group of young mice were given iron prior to the rh‐IGF‐1 injections to ensure sufficient available iron.No differences in overall body or organ weights were observed. In the young mice erythropoiesis as measured by bone marrow CFU‐E, reticulocytes and haematocrit did not differ between rh‐IGF‐1 group and controls. When iron alone was given, reticulocytes (P < 0.05) and haematocrit (P < 0.0001) increased significantly, but no further stimulation was seen when rh‐IGF‐1 injections were given in addition to iron. The adult female mice responded with significantly increased erythropoiesis as judged by increased reticulocyte counts following rh‐IGF‐1 injections (P < 0.001). No significant effect upon CFU‐E and haematocrit was detected. The reticulocyte response was more pronounced at 96 than at 60 h after the first rh‐IGF‐1 injection. SiEPO was significantly (P < 0.01) lower in the adult 96 h rh‐IGF‐1 group than in the appropriate control group.In conclusion parenteral iron significantly increased haematocrit in unweaned mice. Short time rh‐IGF‐1 treatment did not stimulate erythropoiesis in these rapidly growing mice, whether or not iron supplementation had been given. In the adult mice, short time rh‐IGF‐1 treatment stimulated in vivo erythropoiesis as shown by a reticulocyte response. Since the siEPO levels dropped in the adult treatment group the increase in reticulocytes suggests a directly stimulatory action of rh‐IGF‐1 upon erythropoiesis.