Growth hormone-dependent insulin-like growth factor (IGF) binding protein both inhibits and potentiates IGF-I-stimulated DNA synthesis in human skin fibroblasts.
This study investigates the effects of BP-53, the acid-stable IGF-binding subunit of the circulating 150 kDa IGF-binding protein complex, on IGF-I-stimulated thymidine incorporation by neonatal human skin fibroblasts. When cells were incubated for 24 h with IGF-I in serum-free medium, and thymidine incorporation studied over the final 4-h period, maximal stimulation (4- to 7-fold) was seen with 30 ng/ml IGF-I, with a half-maximal effect at 6.8 +/- 1.2 ng/ml (SD, n = 4). Co-incubation of IGF-I with increasing concentrations of pure BP-53 caused dose-dependent inhibition of IGF-I-stimulated thymidine incorporation, which was complete when IGF-I and BP-53 were equimolar. In contrast, preincubation of cells with BP-53 for 8-48 h before adding IGF-I resulted in a potentiation of the subsequent IGF-I effect. The potentiation was maximal (2-fold) at a BP-53 concentration of 150 ng/ml, and appeared to act by increasing the maximal rate of thymidine incorporation rather than the sensitivity of this process to IGF-I. Since neonatal fibroblasts produce a protein which is identical to BP-53 in size and immunoreactivity, these results suggest an autocrine role for BP-53 in regulating fibroblast responsiveness to IGF-I.
De Mellow
J S
JS
Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Baxter
R C
RC
D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007700:Kinetics; D008297:Male; D011972:Receptor, Insulin / Q000502:physiology*; D017451:Receptors, Somatomedin; D012867:Skin / Q000378:metabolism; D013002:Somatomedins / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D011972:Receptor, Insulin; D013936:Thymidine