Insulin-like growth factors promote DNA synthesis and support cell viability in fetal hemopoietic tissue by paracrine mechanisms.
There is significant evidence that the insulin-like growth factors (IGF) play a role in both murine and human hemopoiesis. In order to better define the nature and mechanisms of these effects, we have used a serum-free system to examine DNA synthesis and cell replication in murine hemopoietic cells. Cell preparations from 13-day fetal mice livers were incubated in serum-free DMEM alone or with erythropoietin (Epo) 0.5 U/ml, recombinant human IGF-I, purified IGF-II, or recombinant human growth hormone (GH) in various doses, and [3H]thymidine added for the last 3 hr of 21-hr incubation. Cell distribution was over 80% erythroid or erythroblasts. IGF-I and IGF-II promoted thymidine incorporation into cells at a half-maximal dose of 3 and 1 nM respectively, IGF-II with a maximum potency 65% of IGF-I; insulin stimulated at a half-maximum dose of 100 nM, with similar maximum effect to IGF-I, and their effects were not additive. GH was stimulatory at 1 microM. Epo was 2-9 times as effective as IGF-I and their effects were not additive. A monoclonal antibody to IGF-I reduced the effect of IGF-I by 50-80%, had no effect on Epo, and abolished the GH effect. Separation of erythroid cells and precursors from accessory and other liver cells did not alter the response to IGF-I. Cell counts increased in response to IGF-I or Epo, and cell viability was maintained by IGF-I compared to control medium.(ABSTRACT TRUNCATED AT 250 WORDS)
Werther
G A
GA
Department of Endocrinology and Diabetes, Royal Children's Hospital, Parkville, Victoria, Australia.
Haynes
K
K
Johnson
G R
GR
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D013997:Time Factors
D007328:Insulin; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA