Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production.
We examined human growth hormone's (hGH) effect on mitogenesis in cultured 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% [SEM]) (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 (Sm1.2) dose dependently blunted TI stimulated by 10 ng/ml hGH or IGF-I (at 1:1000, 38 +/- 6.5% and 30 +/- 14% reduction, respectively). Sm1.2 also reduced cell replication by both 10 ng/ml hGH and IGF-I, respectively, to 32% and 42% of stimulated values. Dexamethasone (0.1 microM) 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.
Cook
J J
JJ
Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Australia.
Haynes
K M
KM
Werther
G A
GA
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D013002:Somatomedins / Q000096:biosynthesis*; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013936:Thymidine