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Insulin-like growth factor I/somatomedin-C (IGF-I/SM-C) and glucocorticoids synergistically regulate mitosis in competent human fibroblasts.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 1983 Aug; Vol. 116 (2), pp. 191-7. - Publication Year :
- 1983
-
Abstract
- 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.
- Subjects :
- Adult
Cell Division drug effects
Cells, Cultured
Dexamethasone pharmacology
Drug Synergism
Fibroblasts
Humans
Hydrocortisone pharmacology
Insulin metabolism
Insulin-Like Growth Factor I
Male
Peptides metabolism
Receptors, Cell Surface metabolism
Receptors, Somatomedin
Somatomedins metabolism
Thymidine metabolism
Glucocorticoids pharmacology
Insulin pharmacology
Mitosis drug effects
Peptides pharmacology
Somatomedins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9541
- Volume :
- 116
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 6306016
- Full Text :
- https://doi.org/10.1002/jcp.1041160210