TY - JOUR
T1 - Aging alters somatomedin-c-dexamethasone synergism in the stimulation of deoxyribonucleic acid synthesis and replication of cultured human fibroblasts
AU - Conover, Cheryl A.
AU - Rosenfeld, Ron G.
AU - Hintz, Raymond L.
PY - 1985/9
Y1 - 1985/9
N2 - The effects of dexamethasone on somatomedin- C (SM-C) stimulation of [3H]thymidine incorporation and cell replication were studied in early passage fibroblasts from normal donors, aged 7-24 yr (young) and 85-96 yr (old), and one patient with progeria. Preincubation of cells from young donors with dexamethasone dramatically enhanced SM-C stimulation of [3H]thymidine incorporation [e.g. 19- vs. 3-fold in serum-free medium; 66- vs. 14-fold in 0.25% human hypopituitary serum (HHS)], with no alteration in the timing of peak thymidine incorporation. In contrast, preincubation of cells from old and progeric donors with dexamethasone resulted in a 6- to 12-hr lengthening of the prereplicative period and, generally, little or no synergism with SM-C. Cells from old and progeric donors had a normal replicative response to SM-C with or without 0.25% HHS. In cells from young donors, dexamethasone enhanced the SM-C-stimulated increase in cell number 32%49% in serum-free medium and 70-189% in 0.25% HHS. In comparison, dexamethasone had no potentiating effect on SM-C stimulation of multiplication of cells from old and progeric donors. These data indicate that dexamethasone and SM-C are synergistic in stimulating DNA synthesis and replication of fibroblasts from young donors, but that this synergism is impaired in cells from aged and progeric donors.
AB - The effects of dexamethasone on somatomedin- C (SM-C) stimulation of [3H]thymidine incorporation and cell replication were studied in early passage fibroblasts from normal donors, aged 7-24 yr (young) and 85-96 yr (old), and one patient with progeria. Preincubation of cells from young donors with dexamethasone dramatically enhanced SM-C stimulation of [3H]thymidine incorporation [e.g. 19- vs. 3-fold in serum-free medium; 66- vs. 14-fold in 0.25% human hypopituitary serum (HHS)], with no alteration in the timing of peak thymidine incorporation. In contrast, preincubation of cells from old and progeric donors with dexamethasone resulted in a 6- to 12-hr lengthening of the prereplicative period and, generally, little or no synergism with SM-C. Cells from old and progeric donors had a normal replicative response to SM-C with or without 0.25% HHS. In cells from young donors, dexamethasone enhanced the SM-C-stimulated increase in cell number 32%49% in serum-free medium and 70-189% in 0.25% HHS. In comparison, dexamethasone had no potentiating effect on SM-C stimulation of multiplication of cells from old and progeric donors. These data indicate that dexamethasone and SM-C are synergistic in stimulating DNA synthesis and replication of fibroblasts from young donors, but that this synergism is impaired in cells from aged and progeric donors.
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U2 - 10.1210/jcem-61-3-423
DO - 10.1210/jcem-61-3-423
M3 - Article
C2 - 4040529
AN - SCOPUS:0021966953
SN - 0021-972X
VL - 61
SP - 423
EP - 428
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -