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Developmental patterns of insulin-like growth factor-I and -II synthesis and regulation in rat fibroblasts

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Abstract

Insulin-like growth factor-I (IGF-I) and IGF-II are chemically similar polypeptides with related receptor specificity and in vitro biological activity1. IGF-I and IGF-II have a 62% amino acid sequence identity and are 38–48% homologous with the A and B domains of human proinsulin. They can be distinguished by specific radioimmunoassays, appear to have different patterns of hormonal regulation, and presumably serve different in vivo biological functions. Plasma IGF-I levels reflect circulating concentrations of pituitary growth hormone (GH), and exogenous IGF-I substitutes for GH in inducing somatic and skeletal growth in GH-deficient rats2. Several recent observations in rats have suggested a possible role for IGF-II in fetal growth. IGF-II levels are 20- to 100-fold higher in fetal rat serum than in maternal serum and decline within days after birth3. IGF-I exhibits the reciprocal developmental pattern—low in the early neonate, rising to adult levels by approximately 4 weeks of age4,5. We recently reported6 that cultured rat embryo fibroblasts synthesize large amounts of multiplication-stimulating activity (MSA or rIGF-II), the rat homologue of human IGF-II7. We now demonstrate that fibroblast cultures established from rats 2 to 50 days of age mimic the developmental switch from IGF-II to IGF-I production observed in serum. In addition, we show that placental lactogen (PL) but not GH stimulates IGF-II synthesis in fetal fibroblasts. By contrast, both GH and PL stimulate IGF-I synthesis in fibroblasts from older rats with no effect on IGF-II synthesis. Stimulation of IGF-II synthesis in fetal fibroblasts by PL provides a mechanism whereby PL may regulate fetal growth.

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Authors and Affiliations

  1. Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20205, USA

    S. O. Adams & S. P. Nissley

  2. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, 27710, USA

    S. Handwerger

  3. Laboratory of Biochemical Pharmacology, National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20205, USA

    M. M. Rechler

Authors
  1. S. O. Adams
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  2. S. P. Nissley
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  3. S. Handwerger
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  4. M. M. Rechler
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Adams, S., Nissley, S., Handwerger, S. et al. Developmental patterns of insulin-like growth factor-I and -II synthesis and regulation in rat fibroblasts. Nature 302, 150–152 (1983). https://doi.org/10.1038/302150a0

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