Mitogenic effects of growth hormone in cultured human fibroblasts: evidence for action via local insulin-like growth factor 1 production

Abstract

We examined human growth hormone's (hGH) effect on mitogenesis in cbltured human fibroblasts, and the role of local insulin-like growth factor I (IGF-I). With 0.5% human hypopituitary serum (HPS), hGH increased thymidine incorporation (TI) over serum-free medium dose responsively, with half-maximal effect at 10 ng/ml (0.5 nM) (hGH 127+/-8.8%; IGF-I 107+/-(1.7% [SEMI) (n = 10). Similarly, with 0.5% HPS, hGH and IGF-I increased cell replication by 172+/-8.2% and 169+/-25%, respectively (n = 4). Specific IGF-I monoclonal antibody (Sml.2) dose dependently blunted TI stimulated by 10 ng/ml hGH or IGF-I (at 1:1000, 38+/-6.5% and 30+/-14% reduction, respectively). Sml.2 also reduced cell replication by both 10 ng/ml hGH and IGF-I, respectively, to 32% and 42% of stimulated values. Dexamethasone (0.1 MiM) synergistically enhanced TI by both IGF-I and hGH. A 28-h time course for TI showed that hGH stimulated a similar peak to IGF-I, lagging in its effect by 4-10 h. We have provided further evidence that hGH stimulates growth of cultured human fibroblasts via local IGF-I production, consistent with IGF-I's paracrine-autocrine role.