Hormonal control of the replication of human fetal fibroblasts: Role of somatomedin C/insulin‐like growth factor I

Sparse cultures of fetal and postnatal human fibroblasts were equivalent in their responsiveness to the mitogenic action of somatomedin C/insulin‐like growth factor I (SM‐C/IGF‐I). At both developmental stages, the addition of SM‐C/IGF‐I (100 ng/ml) increased cell number at day 3 1.4‐fold in serum‐free medium and 2‐fold in the presence of 0.25% human hypopituitary serum. Furthermore, dose‐response curves indicated that there was no difference in the sensitivity of fetal and postnatal fibroblasts to the growth‐promoting effects of SM‐C/IGF‐I, with a half‐maximal response occuring at 6 ng/ml SM‐C/IGF I. This biological action of SM‐C/IGF‐I correlated with SM‐C/IGF‐I binding to fetal and postnatal fibroblast monolayers. Epidermal growth factor (EGF) and platelet‐derived growth factor (PDGF) also stimulated replication of fetal and postnatal fibroblasts. The mitogenic effects of SM‐C/IGF‐I, EGF, and PDGF were additive. Dexamethasone, which alone had no effect, was synergistic with SM‐C/IGF‐I in stimulating replication of postnatal fibroblasts. The combination of SM‐C/IGF‐I (100 ng/ml), dexamethasone (10⁻⁷ M), EGF (10 ng/ml), and PDGF (5 ng/ml) had the same mitogenic effectiveness as 10% calf serum (CS) in postnatal cells. In marked contrast, there was no mitogenic interaction between SM‐C/IGF‐I and dexamethasone in fetal fibroblasts. In fetal cells, SM‐C/IGF‐I + EGF + PDGF ± dexamethasone could only account for 50% of the activity of 10% CS. Moreover, fetal cells were 50–100% more responsive than postnatal cells to the proliferative effect of serum.