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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Oct;86(19):7451–7455. doi: 10.1073/pnas.86.19.7451

Developmental regulation of the rat insulin-like growth factor I receptor gene.

H Werner 1, M Woloschak 1, M Adamo 1, Z Shen-Orr 1, C T Roberts Jr 1, D LeRoith 1
PMCID: PMC298082  PMID: 2477843

Abstract

We have investigated the developmental regulation of the rat insulin-like growth factor I (IGF-I) receptor gene in various tissues using a sensitive and specific solution hybridization/RNase protection assay. For this purpose we characterized rat IGF-I receptor cDNAs that were cloned from a simian virus 40-transformed rat granulosa cell cDNA library. The specific cDNA clone used in these studies encoded the putative signal peptide and the first 53 amino acids of the alpha subunit and was approximately 94% homologous to its human counterpart. IGF-I receptor gene expression was studied during the perinatal period and at various intervals until early adulthood. Overall, steady-state IGF-I receptor mRNA levels decreased dramatically during postnatal development; however, the extent of the decrease differed among the various tissues studied. In contrast to receptor mRNA levels, IGF-I mRNA levels increased in some of the same tissues. The molecular mechanisms underlying this apparent divergent transcriptional control of the IGF-I and IGF-I receptor genes warrant further study.

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Selected References

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  1. Adamo M., Lowe W. L., Jr, LeRoith D., Roberts C. T., Jr Insulin-like growth factor I messenger ribonucleic acids with alternative 5'-untranslated regions are differentially expressed during development of the rat. Endocrinology. 1989 Jun;124(6):2737–2744. doi: 10.1210/endo-124-6-2737. [DOI] [PubMed] [Google Scholar]
  2. Alexandrides T., Moses A. C., Smith R. J. Developmental expression of receptors for insulin, insulin-like growth factor I (IGF-I), and IGF-II in rat skeletal muscle. Endocrinology. 1989 Feb;124(2):1064–1076. doi: 10.1210/endo-124-2-1064. [DOI] [PubMed] [Google Scholar]
  3. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bassas L., Lesniak M. A., Serrano J., Roth J., de Pablo F. Developmental regulation of insulin and type I insulin-like growth factor receptors and absence of type II receptors in chicken embryo tissues. Diabetes. 1988 May;37(5):637–644. doi: 10.2337/diab.37.5.637. [DOI] [PubMed] [Google Scholar]
  5. Bassas L., de Pablo F., Lesniak M. A., Roth J. Ontogeny of receptors for insulin-like peptides in chick embryo tissues: early dominance of insulin-like growth factor over insulin receptors in brain. Endocrinology. 1985 Dec;117(6):2321–2329. doi: 10.1210/endo-117-6-2321. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Brunetti A., Maddux B. A., Wong K. Y., Goldfine I. D. Muscle cell differentiation is associated with increased insulin receptor biosynthesis and messenger RNA levels. J Clin Invest. 1989 Jan;83(1):192–198. doi: 10.1172/JCI113858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chernausek S. D., Beach D. C., Banach W., Sperling M. A. Characteristics of hepatic receptors for somatomedin-C/insulin-like growth factor I and insulin in the developing human. J Clin Endocrinol Metab. 1987 Apr;64(4):737–743. doi: 10.1210/jcem-64-4-737. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Furlanetto R. W., DiCarlo J. N., Wisehart C. The type II insulin-like growth factor receptor does not mediate deoxyribonucleic acid synthesis in human fibroblasts. J Clin Endocrinol Metab. 1987 Jun;64(6):1142–1149. doi: 10.1210/jcem-64-6-1142. [DOI] [PubMed] [Google Scholar]
  11. Goldstein B. J., Muller-Wieland D., Kahn C. R. Variation in insulin receptor messenger ribonucleic acid expression in human and rodent tissues. Mol Endocrinol. 1987 Nov;1(11):759–766. doi: 10.1210/mend-1-11-759. [DOI] [PubMed] [Google Scholar]
  12. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  13. Isaksson O. G., Lindahl A., Nilsson A., Isgaard J. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev. 1987 Nov;8(4):426–438. doi: 10.1210/edrv-8-4-426. [DOI] [PubMed] [Google Scholar]
  14. Jacobs S., Kull F. C., Jr, Earp H. S., Svoboda M. E., Van Wyk J. J., Cuatrecasas P. Somatomedin-C stimulates the phosphorylation of the beta-subunit of its own receptor. J Biol Chem. 1983 Aug 25;258(16):9581–9584. [PubMed] [Google Scholar]
  15. Kahn C. R. The molecular mechanism of insulin action. Annu Rev Med. 1985;36:429–451. doi: 10.1146/annurev.me.36.020185.002241. [DOI] [PubMed] [Google Scholar]
  16. Lowe W. L., Jr, Lasky S. R., LeRoith D., Roberts C. T., Jr Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E-peptides: evidence for differential processing and regulation in liver. Mol Endocrinol. 1988 Jun;2(6):528–535. doi: 10.1210/mend-2-6-528. [DOI] [PubMed] [Google Scholar]
  17. Lowe W. L., Jr, Roberts C. T., Jr, Lasky S. R., LeRoith D. Differential expression of alternative 5' untranslated regions in mRNAs encoding rat insulin-like growth factor I. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8946–8950. doi: 10.1073/pnas.84.24.8946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lowe W. L., Jr, Schaffner A. E., Roberts C. T., Jr, LeRoith D. Developmental regulation of somatostatin gene expression in the brain is region specific. Mol Endocrinol. 1987 Feb;1(2):181–187. doi: 10.1210/mend-1-2-181. [DOI] [PubMed] [Google Scholar]
  19. Massagué J., Czech M. P. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem. 1982 May 10;257(9):5038–5045. [PubMed] [Google Scholar]
  20. Pomerance M., Gavaret J. M., Jacquemin C., Matricon C., Toru-Delbauffe D., Pierre M. Insulin and insulin-like growth factor 1 receptors during postnatal development of rat brain. Brain Res. 1988 Jul 1;470(1):77–83. doi: 10.1016/0165-3806(88)90203-9. [DOI] [PubMed] [Google Scholar]
  21. Rechler M. M., Nissley S. P., Roth J. Hormonal regulation of human growth. N Engl J Med. 1987 Apr 9;316(15):941–943. doi: 10.1056/NEJM198704093161510. [DOI] [PubMed] [Google Scholar]
  22. Rechler M. M., Nissley S. P. The nature and regulation of the receptors for insulin-like growth factors. Annu Rev Physiol. 1985;47:425–442. doi: 10.1146/annurev.ph.47.030185.002233. [DOI] [PubMed] [Google Scholar]
  23. Sara V. R., Hall K., Lins P. E., Fryklund L. Serum levels of immunoreactive somatomedin A in the rat: some developmental aspects. Endocrinology. 1980 Aug;107(2):622–625. doi: 10.1210/endo-107-2-622. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Shimizu M., Torti F., Roth R. A. Characterization of the insulin and insulin-like growth factor receptors and responsitivity of a fibroblast/adipocyte cell line before and after differentiation. Biochem Biophys Res Commun. 1986 May 29;137(1):552–558. doi: 10.1016/0006-291x(86)91246-5. [DOI] [PubMed] [Google Scholar]
  26. Steele-Perkins G., Turner J., Edman J. C., Hari J., Pierce S. B., Stover C., Rutter W. J., Roth R. A. Expression and characterization of a functional human insulin-like growth factor I receptor. J Biol Chem. 1988 Aug 15;263(23):11486–11492. [PubMed] [Google Scholar]
  27. Ullrich A., Gray A., Tam A. W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Le Bon T., Kathuria S., Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503–2512. doi: 10.1002/j.1460-2075.1986.tb04528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Werner H., Adamo M., Lowe W. L., Jr, Roberts C. T., Jr, LeRoith D. Developmental regulation of rat brain/Hep G2 glucose transporter gene expression. Mol Endocrinol. 1989 Feb;3(2):273–279. doi: 10.1210/mend-3-2-273. [DOI] [PubMed] [Google Scholar]
  29. Yip C. C., Hsu H., Patel R. G., Hawley D. M., Maddux B. A., Goldfine I. D. Localization of the insulin-binding site to the cysteine-rich region of the insulin receptor alpha-subunit. Biochem Biophys Res Commun. 1988 Nov 30;157(1):321–329. doi: 10.1016/s0006-291x(88)80050-0. [DOI] [PubMed] [Google Scholar]
  30. Zick Y., Sasaki N., Rees-Jones R. W., Grunberger G., Nissley S. P., Rechler M. M. Insulin-like growth factor-I (IGF-I) stimulates tyrosine kinase activity in purified receptors from a rat liver cell line. Biochem Biophys Res Commun. 1984 Feb 29;119(1):6–13. doi: 10.1016/0006-291x(84)91610-3. [DOI] [PubMed] [Google Scholar]
  31. Zilberstein M., Chou J. Y., Lowe W. L., Jr, Shen-Orr Z., Roberts C. T., Jr, LeRoith D., Catt K. J. Expression of insulin-like growth factor-I and its receptor by SV40-transformed rat granulosa cells. Mol Endocrinol. 1989 Sep;3(9):1488–1497. doi: 10.1210/mend-3-9-1488. [DOI] [PubMed] [Google Scholar]

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