Multihormonal Regulation of IGFBP-1 Promoter Activity

  • David R. Powell
  • Phillip D. K. Lee
  • Adisak Suwanichkul
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 343)


Insulin-like growth factor binding protein-1 (IGFBP-1) is a 25 kiloDalton protein which can compete with IGF receptors for binding of IGF-I and IGF-II peptides. Such high affinity binding allows IGFBP-1 to influence IGF action; IGFBP-1 can inhibit or potentiate the effects of IGF peptides depending on experimental conditions and on post-translational modifications of this binding protein (1). IGFBP-1 is expressed in a tissue-specific manner, with significant expression essentially limited to liver and uterus in most individuals (2,3).


Promoter Activity Phosphoenolpyruvate Carboxykinase cAMP Effect PEPCK Gene CGTCA Motif 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lee, P.D.K., Conover, C.A., and Powell, D.R., Regulation and function of insulin-like growth factor binding protein-1, Proc. Soc. Exp. Biol. Med. ,in press.Google Scholar
  2. 2.
    Brinkman, A., Groffen, C., Kortleve, D.J., Geurts van Kessel, A., and Drop, S.L.S., Isolation and characterization of a cDNA encoding the low MWIGFBP (IBP-1). EMBO J 7:2417–2423 (1988).PubMedGoogle Scholar
  3. 3.
    Mohn, K., Melby, A., Tewari, D., Laz, T., and Taub, R. The gene encoding IGFBP1 is rapidly and highly induced in regenerating liver. Mol. Cell. Biol. 11:1393–1401 (1991).PubMedGoogle Scholar
  4. 4.
    Drop, S.L.S., Kortleve, D.J., and Guyda, H.J., Immunoassay of a somatomedin BP from human amniotic fluid: levels in fetal, neonatal and adult sera. J. Clin. Endocrinol. Metab. 59:908–915 (1984).PubMedCrossRefGoogle Scholar
  5. 5.
    Conover, C.A., Butler, P.C., Wang, M., Rizza, R.A., and Lee, P.D.K., Lack of growth hormone effect on insulin-associated suppression of IGFBP-1 in humans. Diabetes 39:1251–1256 (1990).PubMedCrossRefGoogle Scholar
  6. 6.
    Lewitt, M.S., Denyer, G.S., Cooney, G.J., and Baxter, R.C., Insulin-like growth factor binding protein-1 modulates blood glucose levels. Endocrinol. 129:2254–2256 (1991).CrossRefGoogle Scholar
  7. 7.
    Sasaki, K., Cripe, T.P., Koch, S.R., Andreone, T.L., Peterson, D.D., and Granner, D.K., Multihormonal regulation of PEPCK gene transcription. J. Biol. Chem. 259:15242–15251 (1984).PubMedGoogle Scholar
  8. 8.
    Magnuson, M.A., Quinn, P.G., and Granner, D.K., Multihormonal regulation of phosphoenolpyruvate carboxykinase-CAT fusion gene. J. Biol. Chem. 262:14917–14920 (1987).PubMedGoogle Scholar
  9. 9.
    Liu, J., Park, E.A., Gurney, A.L., Roesler, W.J., and Hanson, R.W., cAMP induction of PEPCK gene transcription is mediated by multiple promoter elements. J. Biol. Chem. 266:19095–19102 (1991).PubMedGoogle Scholar
  10. 10.
    O’Brien, R.M., Lucas, P.C., Forest, C.D., Magnuson, M.A., and Granner, D.K., Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. Science 249:533–537 (1990).PubMedCrossRefGoogle Scholar
  11. 11.
    Conover, C.A., Divertie, G.D., and Lee, P.D.K., Cortisol increases plasma insulin-like growth factor binding protein-1 in humans. Acta Endocrinol. ,in press.Google Scholar
  12. 12.
    Luo, J., Reid, R.E., and Murphy, L.J., Dexamethasone increases hepatic IGFBP-1 mRNA and serum IGFBP-1 concentrations in the rat. Endocrinol. 127:1456–1462 (1990).CrossRefGoogle Scholar
  13. 13.
    Ooi, G.T., Tseng, L.Y.-H., Tran, M.Q., and Rechler, M.M., Insulin rapidly decreases IGFBP-1 gene transcription in streptozotocin-diabetic rats. Mol. Endocrinol 6:2219–2228 (1992).PubMedCrossRefGoogle Scholar
  14. 14.
    Lewitt, M.S., and Baxter, R.C., Regulation of growth hormone-independent IGFBP (BP-28) in cultured human fetal liver explants. J. Clin. Endocrinol. Metab. 69:246–252 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    Orlowski, C.C., Ooi, G.T., and Rechler, M.M., Dexamethasone stimulates transcription of the IGFBP-1 gene in H4-II-E rat hepatoma cells. Mol. Endocrinol. 4:1592–1599 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    Powell, D.R., Suwanichkul, A., Cubbage, M.L., DePaolis, L.A., Snuggs, M.B., and Lee, P.D.K., Insulin inhibits transcription of the human gene for IGFBP-1. J. Biol. Chem. 266:18868–18876 (1991).PubMedGoogle Scholar
  17. 17.
    Unterman, T.G., (Dehler, D.T., Murphy, L.J., and Lacson, R.G., Multihormonal regulation of IGFBP-1 in rat H4IIE hepatoma cells: The dominant role of insulin. Endocrinol. 128:2693–2701 (1991).CrossRefGoogle Scholar
  18. 18.
    Powell, D.R., Lee, P.D.K., DePaolis, L.A., Morris, S.L., and Suwanichkul, A., Dexamethasone stimulates expression of IGFBP-1 in HEP G2 human hepatoma cells. Growth Reg. 3:11–13 (1993).Google Scholar
  19. 19.
    Suwanichkul, A., DePaolis, L.A., Lee, P.D.K., and Powell, D.R., Identification of a promoter element which participates in cAMP-stimulated expression of human IGFBP-1. J. Biol. Chem. ,in press.Google Scholar
  20. 20.
    Imai, E., Miner, J.N., Mitchell, J.A., Yamamoto, K.R., and Granner, D.K., Glucoœrticoid receptorcAMP response element binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids. J. Biol. Chem. 268:5353–5356 (1993).PubMedGoogle Scholar
  21. 21.
    Park, E.A., Roesler, W.J., Liu, J., Klemm, D.L., Gurney, A.L., Thatcher, J.D., Shuman, J., Friedman, A., and Hanson, R.W., The role of the CCAAT/Enhancer binding-protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP). Mol. Cell. Biol. 10:6264–6272 (1990).PubMedGoogle Scholar
  22. 22.
    Suwanichkul, A., Cubbage, M.L., and Powell, D.R., The promoter of the human gene for insulin-like growth factor binding protein-1. J. Biol. Chem. 265:21185–21193 (1990).PubMedGoogle Scholar
  23. 23.
    déWet, J.,Wood, K., De Luca, M., Helinski, D., and Subramani, S., Firefly luciferase gene: Structure and expression in mammalian cells. Mol. Cell. Biol. 7:725–737 (1987).Google Scholar
  24. 24.
    Borman, C., Moffat, L., and Howard, B., Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol. Cell. Biol. 2:1044–1051 (1982).Google Scholar
  25. 25.
    Needleman, S.B., and Wunsch, C.D., A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48:443–453 (1970).PubMedCrossRefGoogle Scholar
  26. 26.
    Unterman, T.G., Lacson, R.G., McGary, E., Whalen, C., Purple, C., and Goswami, R.G., Cloning of the rat IGFBP-1 gene and analysis of its’ 5’ promoter region. Biochem. Biophys. Res. Comm. 185:993–999 (1992).PubMedCrossRefGoogle Scholar
  27. 27.
    Mendel, D.B., and Crabtree, G.R., HNF-1, a member of a novel class of dimerizing homeodomain proteins. J. Biol. Chem. 266:677–680 (1991).PubMedGoogle Scholar
  28. 28.
    Powell, D.R., and Suwanichkul, A., HNF1 activates transcription of the human gene for IGFBP-1. DNA Cell Biol. 12:283–289 (1993).PubMedCrossRefGoogle Scholar
  29. 29.
    Blumenfeld, M., Maury, M., Chouard, T., Yaniv, M., and Condamine, H., HNF1 shows a wider distribution than products of its known target genes in developing mouse. Development 113:589–599 (1991).PubMedGoogle Scholar
  30. 30.
    De Simone, V., DeMagistris, L., Lazzaro, D., Gerstner, J., Monaci, P., Nicosia, N., and Cortese, R., LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia. EMBOJ 10:1435–1444 (1991).Google Scholar
  31. 31.
    Chin, E., Zhou, J., and Bondy, C., Anatomical relationships in the patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression in the rat kidney. Endocrinol 130:3237–3245 (1992).CrossRefGoogle Scholar
  32. 32.
    Suikkari, A.-M., Koivisto, V.A., Koistinen, R., Seppala, M., and Yki-Jarvinen, H., Dose-response characteristics for suppression of low MW IGFBP by insulin. J. Clin. Endocrinol. Metab. 68:135–140 (1989).PubMedCrossRefGoogle Scholar
  33. 33.
    Conover, C.A., and Lee, P.D.K., Insulin regulation of IGFBP production in cultured HEP G2 cells. J. Clin. Endocrinol. Metab. 70:1062–1067 (1990).PubMedCrossRefGoogle Scholar
  34. 34.
    Lee, P.D.K., Suwanichkul, A., DePaolis, L.A., Snuggs, M.B., Morris, S.L., and Powell, D.R., IGF suppression of IGFBP-1 production: Evidence for mediation by the type I IGF receptor.. Reg. Peptides, in press. Google Scholar
  35. 35.
    Suwanichkul, A., Morris, S.L., and Powell, D.R., Identification of an insulin responsive element in the promoter of the human gene for IGFBP-1. J. Biol. Chem. ,in press.Google Scholar
  36. 36.
    Johnson, T.M., Rosenberg, M.P., and Meisler, M.H., An insulin-responsive element in the pancreatic enhancer of the amylase gene. J. Biol. Chem. 268:464–468,1993.PubMedGoogle Scholar
  37. 37.
    Hilding, A., Thoren, M., and Hall, K., The effect of glucagon on serum IGFBP-1 levels in GH deficient patients. In: Binoux, M., Zapf, J., eds. 2nd International Workshop on IGFBPs ,Opio, France, 111 (abstract 98B) (1992).Google Scholar
  38. 38.
    Montminy, M.R., Gonzalez, G.A., and Yamamoto, K., Characteristics of the cAMP response unit. Rec. Prog. Hormone Res. 46:219–230 (1990).Google Scholar
  39. 39.
    Habener, J.F., Cyclic AMP response element binding proteins: A cornucopia of transcription factors. Mol. Endocrinol. 4:1087–1094 (1990).PubMedCrossRefGoogle Scholar
  40. 40.
    Imai, E., Stromstedt, P.-E., Quinn, P.G., Carlstedt-Duke, J., Gustafsson, J.-A., and Granner, D.K., Characterization of a complex glucocorticoid response unit in the PEPCK gene. Mol. Cell. Biol. 10:4712–4719 (1990).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • David R. Powell
    • 1
  • Phillip D. K. Lee
    • 1
  • Adisak Suwanichkul
    • 1
  1. 1.Department of PediatricsBaylor College of MedicineHoustonUSA

Personalised recommendations