Insulin‐like growth factor I/somatomedin‐C (IGF‐I/SM‐C) and glucocorticoids synergistically regulate mitosis in competent human fibroblasts

Cheryl A. Conover, Laura A. Dollar, Raymond L. Hintz, Ron G. Rosenfeld

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalJournal of Cellular Physiology
Volume116
Issue number2
DOIs
StatePublished - Aug 1983

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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