TY - JOUR
T1 - Insulin‐like growth factor I/somatomedin‐C (IGF‐I/SM‐C) and glucocorticoids synergistically regulate mitosis in competent human fibroblasts
AU - Conover, Cheryl A.
AU - Dollar, Laura A.
AU - Hintz, Raymond L.
AU - Rosenfeld, Ron G.
PY - 1983/8
Y1 - 1983/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0020546034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0020546034&partnerID=8YFLogxK
U2 - 10.1002/jcp.1041160210
DO - 10.1002/jcp.1041160210
M3 - Article
C2 - 6306016
AN - SCOPUS:0020546034
SN - 0021-9541
VL - 116
SP - 191
EP - 197
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 2
ER -