Aging alters somatomedin-C-dexamethasone synergism in the stimulation of deoxyribonucleic acid synthesis and replication of cultured human fibroblasts

C. A. Conover, Ronald (Ron) Rosenfeld, R. L. Hintz

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)423-428
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume61
Issue number3
StatePublished - 1985
Externally publishedYes

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Fibroblasts
Insulin-Like Growth Factor I
Dexamethasone
Aging of materials
Tissue Donors
DNA
Thymidine
Serum-Free Culture Media
Serum
Progeria
DNA Replication
Cell Count
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Aging alters somatomedin-C-dexamethasone synergism in the stimulation of deoxyribonucleic acid synthesis and replication of cultured human fibroblasts. / Conover, C. A.; Rosenfeld, Ronald (Ron); Hintz, R. L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 61, No. 3, 1985, p. 423-428.

Research output: Contribution to journalArticle

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abstract = "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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