Insulin-like growth factor I/somatomedin-C (IGF-I/SM-C) and glucocorticoids synergistically regulate mitosis in competent human fibroblasts.
In serum-free medium, insulin-like growth factor-I/somatomedin-C (IGF-I/SM-C) was weakly mitogenic for adult human fibroblasts in culture. However, in the presence of 0.5% human hypopituitary serum (HHS), which by itself had little effect, there was a marked dose-dependent response to IGF-I/SM-C with a 10- to 20-fold increase in [3H]thymidine incorporation at 25 ng/ml IFG-I/SM-C. With the further addition of dexamethasone or hydrocortisone to the combination of IGF-I/SM-C + 0.5% HHS, there was a dramatic synergistic effect resulting in a 60- to 70-fold increase in [3H]thymidine incorporation. This stimulation was two times greater than that seen with 20% FCS. In contrast, glucocorticoids had no effect in serum-free medium or with HHS alone. These [3H]thymidine incorporation results were clearly supported by cell replication studies. Dose-response curves for 125I IGF-I/SM-C binding and IGF-I/SM-C stimulation of [3H]thymidine incorporation were similar with 1/2 maximal effects for both at 5 ng/ml. However, the striking synergism seen with glucocorticoids occurred in the absence of any glucocorticoid-induced change in IGF-I/SM-C binding, indicating that the interaction of IGF-I/SM-C and glucocorticoids occurs at a postreceptor level. These data demonstrate that in the presence of a low concentration of HHS, IGF-I/SM-C and glucocorticoids stimulate complete cell cycle traverse and replication of human fibroblasts.
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005347:Fibroblasts; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D005938:Glucocorticoids; D007328:Insulin; D010455:Peptides; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013936:Thymidine; D006854:Hydrocortisone