INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I PREVENT THE MITOGENIC RESPONSE OF CHICK LIMB BUD MESODERM CELLS TO PLATELET-DERIVED GROWTH FACTOR-AA

Platelet-derived growth factor AA (PDGF-AA) increases DNA synthesis by chicken limb bud mesoderm in culture. Preincubation of either mesoderm from whole limb buds (stage 24-25) or mesoderm from the distal tip of the bud (stage 25) in insulin or insulin-like growth factor type I (IGF-I) resulted in increased DNA synthesis compared to control levels in two different types of medium. However, no further increase in DNA synthesis was then induced by PDGF-AA. This was found even when the level of DNA synthesis in IGF-I or insulin-containing medium was below that seen in cells treated only with PDGF. The response to PDGF was not dependent on the presence of serum in the medium. Insulin and IGF-I inhibited expression of the PDGF alpha receptor in mesoderm from whole limb buds. However, this was detected at times after the increase in DNA synthesis in response to PDGF was normally seen. IGF-I did not inhibit expression of the PDGF alpha receptor in mesoderm from distal limb bud tips. Thus, IGF-I and insulin modify the response of limb bud mesoderm to PDGF. The effects of IGF-I and insulin on receptor expression may be dependent on the cell populations present but do not appear to account for modulation of the PDGF-induced mitogenic response. (C) 1995 Academic Press, Inc.