Abstract
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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- Adams S. O., Nissley S. P., Handwerger S., Rechler M. M. Developmental patterns of insulin-like growth factor-I and -II synthesis and regulation in rat fibroblasts. Nature. 1983 Mar 10;302(5904):150–153. doi: 10.1038/302150a0. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1016/0006-8993(87)90766-9. [DOI] [PubMed] [Google Scholar]
- Birnboim H. C. A rapid alkaline extraction method for the isolation of plasmid DNA. Methods Enzymol. 1983;100:243–255. doi: 10.1016/0076-6879(83)00059-2. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1002/jnr.490080212. [DOI] [PubMed] [Google Scholar]
- Brown A. L., Graham D. E., Nissley S. P., Hill D. J., Strain A. J., Rechler M. M. Developmental regulation of insulin-like growth factor II mRNA in different rat tissues. J Biol Chem. 1986 Oct 5;261(28):13144–13150. [PubMed] [Google Scholar]
- Burgess S. K., 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] [Google Scholar]
- Burgess S. K., Sahyoun N., Blanchard S. G., LeVine H., 3rd, Chang K. J., 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. doi: 10.1083/jcb.102.1.312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burgess S. K., Trimmer P. A., McCarthy K. D. 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. doi: 10.1016/0006-8993(85)90271-9. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- D'Ercole A. J., Stiles A. D., Underwood L. E. 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. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daughaday W. H. 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. doi: 10.3181/00379727-170-41428. [DOI] [PubMed] [Google Scholar]
- Froesch E. R., Schmid C., Schwander J., Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol. 1985;47:443–467. doi: 10.1146/annurev.ph.47.030185.002303. [DOI] [PubMed] [Google Scholar]
- Frunzio R., Chiariotti L., Brown A. L., Graham D. E., Rechler M. M., Bruni C. B. 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] [Google Scholar]
- Gammeltoft S., Haselbacher G. K., Humbel R. E., 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. doi: 10.1002/j.1460-2075.1985.tb04097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glowinski J., Iversen L. L. 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. doi: 10.1111/j.1471-4159.1966.tb09873.x. [DOI] [PubMed] [Google Scholar]
- Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
- Haselbacher G. K., Schwab M. E., Pasi A., Humbel R. E. 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. doi: 10.1073/pnas.82.7.2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hynes M. A., Van Wyk J. J., Brooks P. J., D'Ercole A. J., Jansen M., Lund P. K. 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. doi: 10.1210/mend-1-3-233. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1016/0165-3806(83)90177-3. [DOI] [PubMed] [Google Scholar]
- Lund P. K., Moats-Staats B. M., Hynes M. A., Simmons J. G., Jansen M., D'Ercole A. J., Van Wyk J. J. 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] [Google Scholar]
- Mathews L. S., Norstedt G., Palmiter R. D. 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. doi: 10.1073/pnas.83.24.9343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McMorris F. A., Smith T. M., DeSalvo S., Furlanetto R. W. 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. doi: 10.1073/pnas.83.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. 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. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy L. J., Bell G. I., Friesen H. G. Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology. 1987 Apr;120(4):1279–1282. doi: 10.1210/endo-120-4-1279. [DOI] [PubMed] [Google Scholar]
- Recio-Pinto E., Ishii D. N. 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. doi: 10.1016/0006-8993(84)90246-4. [DOI] [PubMed] [Google Scholar]
- Recio-Pinto E., Rechler M. M., Ishii D. N. 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. doi: 10.1523/JNEUROSCI.06-05-01211.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rigby P. W., 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. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Rinderknecht E., Humbel R. E. Primary structure of human insulin-like growth factor II. FEBS Lett. 1978 May 15;89(2):283–286. doi: 10.1016/0014-5793(78)80237-3. [DOI] [PubMed] [Google Scholar]
- Rinderknecht E., Humbel R. E. 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] [Google Scholar]
- Rotwein P., Pollock K. M., Didier D. K., Krivi G. G. 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] [Google Scholar]
- Sara V. R., 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. doi: 10.1073/pnas.83.13.4904. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sara V. R., 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. doi: 10.1172/JCI110858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sargent T. D., Wu J. R., Sala-Trepat J. M., Wallace R. B., Reyes A. A., Bonner J. The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3256–3260. doi: 10.1073/pnas.76.7.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schoenle E., Zapf J., Humbel R. E., Froesch E. R. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. doi: 10.1038/296252a0. [DOI] [PubMed] [Google Scholar]
- 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] [Google Scholar]
- Soares M. B., Ishii D. N., 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. doi: 10.1093/nar/13.4.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soares M. B., 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. doi: 10.1016/0022-2836(86)90025-2. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]