Localization and regulation of IGF-I and IGF-II mRNA

  • M. A. Hynes
  • P. J. Brooks
  • J. English
  • J. J. Van Wyk
  • P. K. Lund
Conference paper


Insulin-like growth factors I and II (IGF-I and -H) are peptide mitogens that exert a wide range of biological actions in many tissues and cell types. The actions of the IGFs include metabolic and differentiative effects as well as their capacity to stimulate cell proliferation. (Humbel 1984; Froesch et al. 1985; Van Wyk 1984). Traditionally the IGFs were considered as hormones that are transported in the circulation to act on target cells in an endocrine fashion (Humbel 1984; Froesch et al. 1985; Van Wyk et al. 1984). Based on studies of perfused liver (Schwander et al. 1983), liver derived cell lines (Moses et al. 1980), and primary cultures oliver cells (Richmond et al. 1985), the liver was considered the major source of serum IGFs. The IGFs do not appear to be stored in the liver to an appreciable extent, however, since the concentrations of IGFs are higher in blood perfusing the liver than in extracts of liver. More recently, cultured expiants of many tissues in addition to liver have been found to secrete immunoreactive IGFs into media (D’Ercole et al. 1984). Extracts of multiple tissues in addition to liver also contain higher concentrations of immunoreactive IGF than can be attributed to concentrations in blood perfusing the tissues (D’Ercole et al. 1984, 1986). These observations have raised the possibility that in addition to the endocrine actions of IGFs transported to target cells via the circulation, there may be paracrine or autocrine actions of IGFs synthesized locally in multiple tissues (D’Ercole et al. 1984,1986).


Choroid Plexus eDNA Probe Synthetic Oligomer Oligomer Probe Liver Derive Cell Line 
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  1. Bell GI, Gerhard DS, Fong NM, Sanchez-Pescador R, Rall LB (1985) Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous. Proc Natl Acad Sci USA 82: 6450–6454PubMedCrossRefGoogle Scholar
  2. Bell GI, Merryweather JP, Sanchez-Pescador R, Stempien MM, Priestley L, Scott J, Rail LB (1984) Sequence of a cDNA clone encoding human preproinsulin-like growth factor II. Nature 310:775–777PubMedCrossRefGoogle Scholar
  3. Casella SJ, Smith EP, Van Wyk JJ, D’Ercole AJ, Hynes MA, Hoyt EC, Lund PK (1987) Isolation of rat testis cDNAs encoding an insulin-like growth factor I precursor. DNA 6: 325–330PubMedCrossRefGoogle Scholar
  4. D’Ercole AJ, Stiles AD, Underwood LE (1984) Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 81: 935–939PubMedCrossRefGoogle Scholar
  5. D’Ercole AJ, Hill DJ, Strain A, Underwood LE (1986) Tissue and plasma somatomedin-C/insulin-like growth factor I concentrations in the human fetus during the first half of gestation. Pediatrie Res 20: 253–255CrossRefGoogle Scholar
  6. Dull TJ, Gray A, Hayflck JS, Ullrich A (1984) Insulin-like growth factor II precursor gene organization in relation to insulin gene family. Nature 311:777–781CrossRefGoogle Scholar
  7. Froesch ER, Schmid C, Schwander J, Zapf J (1985) Actions of insulin-like growth factors. Anna Rev Physiol 47:443–467CrossRefGoogle Scholar
  8. Frunzio R, Chiariotti L, Brown AL, Graham DE, Rechler MM, Bruni CB (1986) Structure and expression of the rat insulin-like growth factor II (rIGF-II) gene. rIGF-II RNAsare transcribed from two promoters. J Biol Chem 261:17138–17149PubMedGoogle Scholar
  9. Goodman RH, Jacobs JW, Dee PC, Habener JF (1982) Somatostatin-28 encoded in a cloned cDNA obtained from a rat medullary thyroid carcinoma. J Biol Chem 257:1156–1159PubMedGoogle Scholar
  10. Heinrich G, Gros P, Lund PK, Bentley RC, Habener JF (1984) Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid. Endocrinology 115:2176–2181PubMedCrossRefGoogle Scholar
  11. Hynes MA, Van Wyk JJ, Brooks PJ, D’Ercole AJ, Jansen M, Lund PK (1987) Growth hormone dependence of somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II messenger ribonucleic acids. Mol Endocrinol 1: 233–242PubMedCrossRefGoogle Scholar
  12. Humbel RE (1984) Insulin-like growth factors, somatomedins, and multiplication stimulating activity chemistry. In: Li CH (ed) Hormonal Proteins and Peptides: Growth Factors, vol 12. Academic, New York, pp 57–79Google Scholar
  13. Lund PK, Moats-Staats BM, Hynes MA, D’Ercole AJ, Jansen M, Van Wyk JJ (1986) Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem 261:14539–14544PubMedGoogle Scholar
  14. Jansen M, Van Schaik FMA, Richer AT, Bullock B, Woods DE, Gabbay KH, Nussbaum AL, Sussenbach JS, Van den Brande JL (1983) Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature 306:609–611PubMedCrossRefGoogle Scholar
  15. Jansen M, Van Schaik FMA, von Tohl H, Van den Brande JL, Sussenbach JS (1985) Nucleotide sequences of cDNAs encoding precursors of human insulin-like growth factor II (IGF-II) and IGF-II variant. FEBS Lett 179:243–246PubMedCrossRefGoogle Scholar
  16. Maxam A, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci USA 74: 560–564PubMedCrossRefGoogle Scholar
  17. Moses AC, Nissley SP, Short PA, Rechler MM, White RM, Knight AB, Higa OZ (1980) Increased levels of multiplication-stimulating activity, an insulin-like growth factor, in fetal rat serum. Proc Natl Acad Sci USA 77: 3649–3653PubMedCrossRefGoogle Scholar
  18. Ott L (1977) In: Ott L (ed) An Introduction to Statistical Methods and Data Analysis. Duxbury, Belmont, pp 354–407Google Scholar
  19. Richmond RA, Benedict MR, Florini JR, Toly BA (1985) Hormonal regulation of somatomedin secretion by fetal rat hepatocytes in primary culture. Endocrinology 116: 180–188CrossRefGoogle Scholar
  20. Rigby PW, Diekmann M, Rhodes C, Berg P (1977) Labeling deoxyribonucleic acid to high specific activity in vitroby nick translation with DNA Polymerase I. J Mol Biol 113: 237–251PubMedCrossRefGoogle Scholar
  21. Roberts CT Jr, Lasky SR, Lowe WL, Seaman WT, LeRoith D (1987) Molecular cloning of rat insulin-like growth factor I complementary deoxyribounucleic acids: differential messenger ribonucleic acid processing and regulation by growth hormone in extra-hepatic tissues. Mol Cell Endocrinol 1: 243–248CrossRefGoogle Scholar
  22. Rotwein P (1986) Two insulin-like growth factor I messenger RNAs are expressed in human liver. Proc Natl Acad Sci USA 83: 77–81PubMedCrossRefGoogle Scholar
  23. Schalch DS, Heinrich UE, Draznin B, Johnson CJ, Miller LL (1979) Role of the liver in regulating somatomedin activity: hormonal effects on the synthesis and release of insulin-like growth factor and its carrier protein by the isolated perfused rat liver. Endocrinology 104:1143–1151PubMedCrossRefGoogle Scholar
  24. Schwander JC, Hauri C, Zapf J, Froesch ER (1983) Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status. Endocrinology 113:297–305PubMedCrossRefGoogle Scholar
  25. Soares MB, Turken A, Ishii D, Mills L, Episkopou V, Cotter S, Zeitlin S, Efstradiatis A (1986) Rat insulin-like growth factor II gene. A single gene with two promoters expressing a multitranscript family. J Mol Biol 192:737–752PubMedCrossRefGoogle Scholar
  26. Ullrich A, Shire J, Chrigwin JM, Pictet R, Tischer E, Rutter WJ, Goodman HM (1977) Ratz insulin genes: construction of plasmids containing the coding sequences. Science 196: 1313–1319PubMedCrossRefGoogle Scholar
  27. Van Wyk JJ (1984) The somatomedins: biological actions and physiologic control mechanisms. In: Li CH (ed) Hormonal Proteins and Peptides: Growth Factors, vol 12. Academic, New York, pp 81–125Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. A. Hynes
    • 1
  • P. J. Brooks
    • 2
  • J. English
    • 2
  • J. J. Van Wyk
    • 3
  • P. K. Lund
    • 2
  1. 1.Howard Hughes Medical Institute Research Laboratory, Neurobiology and Behavior CenterColumbia UniversityNew YorkUSA
  2. 2.Department of Physiology and Curriculum in NeurobiologyUniversity of North CarolinaChapel HillUSA
  3. 3.Department of PediatricsUniversity of North Carolina at Chapel HillChapel HillUSA

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