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Proc Natl Acad Sci U S A. Jan 1988; 85(1): 265–269.
PMCID: PMC279525

Differential expression of insulin-like growth factor genes in rat central nervous system.


A sensitive solution-hybridization assay was used to investigate the expression of genes encoding insulin-like growth factors I and II (IGF-I and -II) in the rat central nervous system (CNS). mRNAs for both IGFs are synthesized throughout the CNS of adult rats but exhibit distinct regional differences for each growth factor. IGF-I mRNA is 8-10 times more abundant in the cervical-thoracic spinal cord and in the olfactory bulb than in whole brain and is enriched 3-fold in the midbrain and cerebellum. IGF-II mRNA is minimally enriched in the medulla-pons and cerebellum but is 3-5 times less abundant in the midbrain and corpus striatum than in total brain. During CNS development the content of IGF-I and IGF-II mRNAs is highest at embryonic day 14 and declines by a factor of 3-4 at birth, to values found in adult brain. Embryonic neurons and glia synthesize IGF-I mRNA during short-term cell culture; only glia produce IGF-II mRNA. These observations show that IGF-I and IGF-II are differentially expressed in the developing and adult CNS and suggest that each growth factor may play a unique role in the mammalian nervous system.

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  • Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978 Apr 25;253(8):2769–2776. [PubMed]
  • Froesch ER, Schmid C, Schwander J, Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol. 1985;47:443–467. [PubMed]
  • Daughaday WH. Divergence of binding sites, in vitro action, and secretory regulation of the somatomedin peptides, IGF-I and IGF-II. Proc Soc Exp Biol Med. 1982 Jul;170(3):257–263. [PubMed]
  • Schoenle E, Zapf J, Humbel RE, Froesch ER. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. [PubMed]
  • Rinderknecht E, Humbel RE. Primary structure of human insulin-like growth factor II. FEBS Lett. 1978 May 15;89(2):283–286. [PubMed]
  • Haselbacher GK, Schwab ME, Pasi A, Humbel RE. Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2153–2157. [PMC free article] [PubMed]
  • Sara VR, Carlsson-Skwirut C, Andersson C, Hall E, Sjögren B, Holmgren A, Jörnvall H. Characterization of somatomedins from human fetal brain: identification of a variant form of insulin-like growth factor I. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4904–4907. [PMC free article] [PubMed]
  • D'Ercole AJ, Stiles AD, Underwood LE. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. [PMC free article] [PubMed]
  • Lund PK, Moats-Staats BM, Hynes MA, Simmons JG, Jansen M, D'Ercole AJ, Van Wyk JJ. Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem. 1986 Nov 5;261(31):14539–14544. [PubMed]
  • Brown AL, Graham DE, Nissley SP, Hill DJ, Strain AJ, Rechler MM. Developmental regulation of insulin-like growth factor II mRNA in different rat tissues. J Biol Chem. 1986 Oct 5;261(28):13144–13150. [PubMed]
  • Soares MB, Ishii DN, Efstratiadis A. Developmental and tissue-specific expression of a family of transcripts related to rat insulin-like growth factor II mRNA. Nucleic Acids Res. 1985 Feb 25;13(4):1119–1134. [PMC free article] [PubMed]
  • Frunzio R, Chiariotti L, Brown AL, Graham DE, Rechler MM, Bruni CB. Structure and expression of the rat insulin-like growth factor II (rIGF-II) gene. rIGF-II RNAs are transcribed from two promoters. J Biol Chem. 1986 Dec 25;261(36):17138–17149. [PubMed]
  • Soares MB, Turken A, Ishii D, Mills L, Episkopou V, Cotter S, Zeitlin S, Efstratiadis A. Rat insulin-like growth factor II gene. A single gene with two promoters expressing a multitranscript family. J Mol Biol. 1986 Dec 20;192(4):737–752. [PubMed]
  • Hynes MA, Van Wyk JJ, Brooks PJ, D'Ercole AJ, Jansen M, Lund PK. Growth hormone dependence of somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II messenger ribonucleic acids. Mol Endocrinol. 1987 Mar;1(3):233–242. [PubMed]
  • Murphy LJ, Bell GI, Friesen HG. Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology. 1987 Apr;120(4):1279–1282. [PubMed]
  • Mathews LS, Norstedt G, Palmiter RD. Regulation of insulin-like growth factor I gene expression by growth hormone. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9343–9347. [PMC free article] [PubMed]
  • Gammeltoft S, Haselbacher GK, Humbel RE, Fehlmann M, Van Obberghen E. Two types of receptor for insulin-like growth factors in mammalian brain. EMBO J. 1985 Dec 16;4(13A):3407–3412. [PMC free article] [PubMed]
  • Burgess SK, Jacobs S, Cuatrecasas P, Sahyoun N. Characterization of a neuronal subtype of insulin-like growth factor I receptor. J Biol Chem. 1987 Feb 5;262(4):1618–1622. [PubMed]
  • Sara VR, Hall K, Misaki M, Fryklund L, Christensen N, Wetterberg L. Ontogenesis of somatomedin and insulin receptors in the human fetus. J Clin Invest. 1983 May;71(5):1084–1094. [PMC free article] [PubMed]
  • Lenoir D, Honegger P. Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures. Brain Res. 1983 Apr;283(2-3):205–213. [PubMed]
  • Aizenman Y, de Vellis J. Brain neurons develop in a serum and glial free environment: effects of transferrin, insulin, insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation. Brain Res. 1987 Mar 17;406(1-2):32–42. [PubMed]
  • McMorris FA, Smith TM, DeSalvo S, Furlanetto RW. Insulin-like growth factor I/somatomedin C: a potent inducer of oligodendrocyte development. Proc Natl Acad Sci U S A. 1986 Feb;83(3):822–826. [PMC free article] [PubMed]
  • Recio-Pinto E, Rechler MM, Ishii DN. Effects of insulin, insulin-like growth factor-II, and nerve growth factor on neurite formation and survival in cultured sympathetic and sensory neurons. J Neurosci. 1986 May;6(5):1211–1219. [PubMed]
  • Bothwell M. Insulin and somatemedin MSA promote nerve growth factor-independent neurite formation by cultured chick dorsal root ganglionic sensory neurons. J Neurosci Res. 1982;8(2-3):225–231. [PubMed]
  • Recio-Pinto E, Ishii DN. Effects of insulin, insulin-like growth factor-II and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. Brain Res. 1984 Jun 8;302(2):323–334. [PubMed]
  • Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem. 1966 Aug;13(8):655–669. [PubMed]
  • Burgess SK, Sahyoun N, Blanchard SG, LeVine H, 3rd, Chang KJ, Cuatrecasas P. Phorbol ester receptors and protein kinase C in primary neuronal cultures: development and stimulation of endogenous phosphorylation. J Cell Biol. 1986 Jan;102(1):312–319. [PMC free article] [PubMed]
  • Burgess SK, Trimmer PA, McCarthy KD. Autoradiographic quantitation of beta-adrenergic receptors on neural cells in primary cultures. II. Comparison of receptors on various types of immunocytochemically identified cells. Brain Res. 1985 May 27;335(1):11–19. [PubMed]
  • Shimatsu A, Rotwein P. Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat insulin-like growth factor I gene. J Biol Chem. 1987 Jun 5;262(16):7894–7900. [PubMed]
  • Sargent TD, Wu JR, Sala-Trepat JM, Wallace RB, Reyes AA, Bonner J. The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3256–3260. [PMC free article] [PubMed]
  • Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. [PubMed]
  • Birnboim HC. A rapid alkaline extraction method for the isolation of plasmid DNA. Methods Enzymol. 1983;100:243–255. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. [PMC free article] [PubMed]
  • Zinn K, DiMaio D, Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PMC free article] [PubMed]
  • Rigby PW, Dieckmann M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. [PubMed]
  • Adams SO, Nissley SP, Handwerger S, Rechler MM. Developmental patterns of insulin-like growth factor-I and -II synthesis and regulation in rat fibroblasts. Nature. 1983 Mar 10;302(5904):150–153. [PubMed]
  • Rotwein P, Pollock KM, Didier DK, Krivi GG. Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. J Biol Chem. 1986 Apr 15;261(11):4828–4832. [PubMed]

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