Effect of insulin-like growth factor (IGF)-I and Des (1-3) IGF-I on the level of IGF binding protein-3 and IGF binding protein-3 mRNA in cultured porcine embryonic muscle cells

Insulin-like growth factor binding protein (IGFBP)-3 effects proliferation and differentiation of numerous cell types by binding to insulin-like growt h factors (IGF) and attenuating their activity or by directly affecting cel ls in an IGF-independent manner. Consequently, IGFBPs produced by specific cells may affect their differentiation and proliferation. In this study we show that embryonic porcine myogenic cells, unlike murine muscle cell lines , produce significant quantities of a binding protein immunologically ident ified as IGFBP-3. Nonfusing cells subcultured from highly fused porcine myo genic cell cultures do not produce detectable IGFBP-3 protein or mRNA, thus suggesting the IGFBP-3 is produced by muscle cells in the porcine myogenic cell cultures. Treatment of porcine myogenic cultures with 20 ng of IGF-I or 20 ng of Des (1-3) IGF-I/ml serum-free media for 24 h results in a three fold reduction in the level of IGFBP-3 in conditioned media. This reduction is not affected by cell density over a sixfold range. Additionally, treatm ent for 24 h with 20 ng of IGF-I/ml media results in a sevenfold decrease i n the steady-state level of IGFBP-3 mRNA. This IGF-I-induced decrease in IG FBP-3 mRNA level appears to be relatively unique to myogenic cells. IGF-I t reatment also causes a fourfold increase in the steady-state level of myoge nin mRNA. This increase in myogenin mRNA suggests that, as expected, IGF-I treatment accelerates differentiation of myogenic cells. The simultaneous d ecrease in IGFBP-3 mRNA and protein that accompanies IGF-I-induced myogenin expression suggests that differentiation of myogenic cells may be preceded or accompanied by decreased production of IGFBP-3. J Cell Physiol 178:227- 234, 1999. (C) 1999 Wiley-Liss, Inc.