Somatomedin C/insulin-like growth factor I binding and action in human fibroblasts aged in culture: Impaired synergism with dexamethasone

Somatomedin C/insulin-like growth factor I (SM-C/IGF-I) binding and action were compared in human fibroblasts serially passaged in vitro. Binding of [¹²⁵I]SM-C/IGF-I was identical in early and late passage cells, with 50% displacement at 4 ng/ml SM-C/IGF-I. Maximal concentrations of SM-C/IGF-I (100 ng/ml) stimulated [³H]thymidine incorporation equally in both early and late passage cells. Furthermore, dose response curves indicated that there was no alteration in the sensitivity of cells to SM-C/IGF-I with age. Preincubation with dexamethasone (10^-7 M) potentiated SM-C/IGF-I's mitogenic effect in early passage cells. In contrast, dexamethasone had no effect on SM-C/IGF-I stimulation of [³H]thymidine incorporation or replication of late passage cells. These data indicate that fibroblasts passaged in vitro have normal SM-C/IGF-I binding and are capable of responding to the mitogenic effect of SM-C/IGF-I. The synergism between SM-C/IGF-I and dexamethasone in stimulating DNA synthesis and replication of early passage fibroblasts is lost, however, in late passage cells.