Insulin-like growth factor-I (IGF-I), a prevalent growth factor secret
ed by bone cells, has important effects on bone remodeling. Hormones a
re known to regulate the synthesis of skeletal IGF-I, but there is lim
ited information about the actions of growth factors on IGF-I synthesi
s. We tested the effects of basic fibroblast growth factor (bFGF), tra
nsforming growth factor-beta1 (TGFbeta1), and platelet-derived growth
factors (PDGF) AA and BB on IGF-I mRNA expression and polypeptide conc
entrations in cultures of osteoblast-enriched (Ob) cells from 22-day-o
ld fetal rat calvariae. Steady state IGF-I mRNA levels were determined
by Northern blot analysis, and IGF-I concentrations were determined i
n acidified and fractionated culture medium by a specific RIA. Treatme
nt of Ob cells with bFGF at 0.06-6 nM, TGFbeta1 at 0.04-4 nM, and PDGF
BB at 0.3-3.3 nM caused a dose-dependent decrease in steady state IGF
-I MRNA. A smaller effect was observed with PDGF AA. The effect was in
itially observed after 6-8 h of treatment and was maximal after 16 h.
Treatment with bFGF at 0.6-6 nM, TGFbeta1 at 0.4-4 nM, and PDGF BB at
0.3-3.3 nM for 24 h decreased IGF-I polypeptide concentrations by 40-8
0%. The effects of bFGF, TGFbeta1, and PDGF BB and AA on IGF-I mRNA we
re independent of protein synthesis and cell division, as they were ob
served in the presence and absence of cycloheximide at 3.6 muM or hydr
oxyurea at 1 mM. Similarly, their inhibitory actions on immunoreactive
IGF-I were not prevented by hydroxyurea. In conclusion, bFGF, TGFbeta
1, PDGF BB, and, to a lesser extent, PDGF AA decrease skeletal IGF-I s
ynthesis by reducing IGF-I transcript levels, and this effect may cont
ribute to their actions on selected aspects of Ob cell function.