Skip to main content
SpringerLink
Log in

Regulation of insulin-like growth factor-l and binding protein-3 expression in oMtla-oGH transgenic mice

  • Papers
  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

Growth hormone (GH)-transgenic mice provide a model for studying hormonal regulation of gene products responsible for efficient lean growth. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (BP-3) are two products involved in mediating the growth promoting actions of GH. Mice carrying the ovine metallothionein la-ovine growth hormone (oMtla-oGH) transgene were used to study GH regulation of IGF-I and PB-3 expression because these mice do not exhibit elevated basal oGH levels without transgene stimulation by exogenous zinc. C57B1/6XCBA mice with (transgenic=TG) and without (control=C) the oMtla-oGH transgene were activated (+Zn) or inactivated (-Zn) by the addition or removal of 25 mM zinc sulfate in the drinking water. Plasma IGF-I and BP-3 levels were determined by radioimmunoassay and western ligand blotting, respectively. Hepatic IGF-I and BP-3 mRNA levels were determined by slot-blot analysis. TG+Zn mice had higher plasma IGF-I (p<0.05) and hepatic IGF-I mRNA (p<0.05) levels as compared to TG-Zn, C+Zn and C-Zn mice. Plasma IGF-I and hepatic IGF-I mRNA levels in TG-Zn mice were not different from C+Zn and C-Zn mice. Removal of Zn decreased hepatic IGF-I mRNA levels to C levels in TG mice. Plasma BP-3 and hepatic BP-3 mRNA levels in TG+Zn mice were increased (p<0.05) as compared to TG-Zn, C-Zn and C+Zn. Plasma BP-3 and hepatic BP-3 mRNA levels did not differ between TG-Zn, C-Zn and C+Zn mice. Expression of the transgene also increased the level of plasma BP-3 during pregnancy as compared to that observed for pregnant C mice. We conclude that oGH regulates IGF-I and BP-3 expression in the oMtla-oGH transgenic mouse model system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adamo, M.L., Shao, Z., Lanau, F., Chen, J.C., Clemmons, D.R., Roberts, C.T., Jr., LeRoith, D. and Fontana, J.A. (1992). Insulin-like growth factor-I and retinoic acid modulation of IGF-binding proteins (IGFBPs): IGFBP-2,-3, and-4 gene expression and protein secretion in a breast cancer cell line.Endocrinol. 131, 1858–66.

    Google Scholar 

  • Albiston, A.L. and Herrington, A.C. (1992) Tissue distribution and regulation of insulin-like growth factor (IGF)-binding protein-3 messenger ribonucleic acid (mRNA) in the rat: comparison with IGF-I mRNA expression.Endocrinol. 130, 492–502.

    Google Scholar 

  • Bar, R.S., Boes, M., Dake, B.L., Sandra, A., Bayne, M., Cascieri, M., and Booth, B.A. (1990) Tissue localization of perfused endothelial cell IGF binding protein is markedly altered by association with IGF-I.Endocrinol. 127, 3243–45.

    Google Scholar 

  • Baxter, R.C., and Martin, J.L. (1989) Binding proteins for insulin-like growth factors: structure, regulation and function.Prog. Growth Factor Res. 1, 49–68.

    Google Scholar 

  • Breier, B.H., Gallaher, B.W. and Gluckman, P.D. (1991) Radioimmunoassay for insulin-like growth factor-I: solutions to some potential problems and pitfalls.J. Endo. 128, 347–57.

    Google Scholar 

  • Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction.Anal. Biochem. 162, 156–9.

    Google Scholar 

  • Clemmons, D.R., Thissen, J.P., Maes, M., Ketelslegers, J.M. and Underwood, L.E. (1989) Insulin-like growth factor infusion into hypophysectomized or protein-deprived rats induces specific IGF binding proteins in serum.Endocrinol. 125, 2967–72.

    Google Scholar 

  • Cohick, W.S. and Clemmons, D.R. (1991) Regulation of insulinlike growth factor binding protein synthesis and secretion in a bovine epithelial cell line.Endocrinol. 129, 1347–54.

    Google Scholar 

  • Copeland, K.C., Underwood, L.E. and Van Wyk, J.J. (1980) Induction of immunoreactive somatomedin-C in human serum by growth hormone: dose response relationships and effect on chromatographic profiles.J. Clin. Endo. & Metab. 50, 690–7.

    Google Scholar 

  • Davenport, M.L., Clemmons, D.R., Miles, M.V., Camacho-Hubner, C., D'Ercole, J.A. and Underwood, L.E. (1990) Regulation of serum insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat pregnancy.Endocrinol. 127 1278–85.

    Google Scholar 

  • Davenport, M.L., Pucilowska, J., Clemmons, D.R., Lundblad, R., Spencer, J.A. and Underwood, L.E. (1992) Tissue-specific expression of insulin-like growth factor binding protein-3 protease activity during rat pregnancy.Endocrinol. 130, 2505–12.

    Google Scholar 

  • De Mellow, J.S.M. and Baxter, R.C. (1988) Growth hormone dependent insulin-like growth factor binding protein both inhibits and potentiates IGF-I stimulated DNA synthesis in skin fibroblasts.Biochem. Biophys. Res. Commun. 156, 199–204.

    Google Scholar 

  • Gargosky, S.E., Nanto-Salonen, K., Tapanainen, P. and Rosenfield, R.G. (1993) Pregnancy in growth hormone-deficient rats: assessment of insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs) and IGFBP protease activity,J. Endo. 136, 479–89.

    Google Scholar 

  • Guler, H.P., Eckardt, K.U., Zapf, J., Bauer, C. and Froesch, E.R. (1989) Insulin-like growth factor I increases glomerular filtration rate and renal plasma flow in man.Acta Endocrinol. 121, 101–6.

    Google Scholar 

  • Gunning, P., Ponte, P., Okayama, H., Engel, J., Blau, H. and Kedes, L. (1983) Isolation and characterization of full length cDNA clones for human α-, β-, and γ-actin mRNA's: skeletal but not cytoplasmic have an amino terminal cysteine that is subsequently removed.Mol. Cell. Biol. 3, 787–95.

    Google Scholar 

  • Hammreman, M.R. (1989) The growth hormone-insulin-like growth factor axis in kidney.Am. J. Physiol. 257, F503–14.

    Google Scholar 

  • Hodgkinson, S.C., Moore, L., Napier, J.R., Davis, S.R., Bass, J.J., and Gluckman, P.D. (1989) Characterization of IGFBPs in ovine tissue fluids.J. Endo. 120, 429–38.

    Google Scholar 

  • Hossenlopp, P., Seurin, D., Segovia-Quinson, B., Hardouin, S. and Binoux, M. (1986) Analysis of serum insulin-like factor binding proteins using western blotting: use of the method for titration of the binding proteins and competitive binding studies.Anal. Biochem. 154, 138–43.

    Google Scholar 

  • Laemmli, U.K. (1970) Cleavage of structural proteins during assembly of the head of bacteriophage T4.Nature 227, 680–5.

    Google Scholar 

  • Lowe, W.L., Jr. (1991) Biological actions of insulin-like growth factors. In LeRoith, D. ed.,Insulin-like Growth Factors: Molecular and Cellular Aspects, pp. 49–85. Boca Raton: CRC Press.

    Google Scholar 

  • Mathews, L.S., Norstedt, G. and Palmiter, R.D. (1986) Regulation of insulin-like growth factor I gene expression by growth hormone.Proc. Natl Acad. Sci. USA 83, 9343–7.

    Google Scholar 

  • McCarthy, T.L., Centrella, M. and Canalis, E. (1990) Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures.J. Biol. Chem. 265, 15353–6.

    Google Scholar 

  • Nilsson, A., Carlsson, B., Isgaard, J., Isaksson, O.G. and Rymo, L. (1990) Regulation by GH of insulin-like growth factor-I mRNA expression in rat epiphyseal growth plate as studied within-situ hybridization.J. Endocrinol. 129, 67–74.

    Google Scholar 

  • Oberbauer, A.M., Currier, T.A., Nancarrow, C.D., Ward, K.A., and Murray, J.D. (1992) Linear bone growth of oMtla-oGH transgenic male mice.Am. J. Physiol. 262, E936–42.

    Google Scholar 

  • Palmiter, R.D., Norstedt, G., Gelinas, R.E., Hammer, R.E. and Brinster, R.L. (1983) Metallothionein-human GH fusion genes stimulate growth of mice.Science 222, 809–14.

    Google Scholar 

  • Pomp, D., Murray, J.D. and Medrano, J.F. (1991) Single day detection of transgenic mice by PCR of toe-clips.Mouse Genome 89, 279.

    Google Scholar 

  • Pomp, D., Nancarrow, C.D., Ward, K.A. and Murray, J.D. (1992) Growth, feed efficiency and body composition of transgenic mice expressing a sheep metallothionein 1a-sheep growth hormone fusion gene.Livest. Prod. Sci. 31, 335–50.

    Google Scholar 

  • Prewitt, T.E., D'Ercole, J.A., Switzer, B.R. and Van Wyk, J.J. (1982) Relationship of serum immunoreactive somatomedian-C to dietary protein and energy in growth rats.J. Nutr. 112, 144–50.

    Google Scholar 

  • Salmon, W.D. and Daughaday, W.H. (1957) A hormonally controlled serum factor which stimulates sulfate incorporation by cartilagein vitro.J. Lab. Clin. Med. 49, 825–36.

    Google Scholar 

  • Sambrook, J., Fritsch, E.F. and Maniatis, T. ed. (1989)Molecular Cloning: a Laboratory Manual,1, 7.37–7.79. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Searle, S.R. (1987)Linear Models for Unbalanced Data New York: John Wiley & Sons.

    Google Scholar 

  • Shanahan, C.M., Rigby, N.W., Murray, J.D., Marshall, J.T., Townrow, C.A., Nancarrow, C.D. and Ward, K.A. (1989) Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice.Mol. Cell. Biol. 9, 5473–9.

    Google Scholar 

  • Straus, D.S. and Takemoto, C.D. (1990) Effect of dietary protein deprivation on insulin-like growth factor (IGF)-I and-II, IGF binding protein-2, and serum albumin gene expression in rat.Endocrinol. 127, 1849–60.

    Google Scholar 

  • Yoon, J., Berry, S.A., Seelig, S. and Towle, H.C. (1990) An inducible nuclear factor binds to a growth hormone-regulated gene.J. Biol. Chem. 265, 19947–54.

    Google Scholar 

  • Zapf, J., Hauri, C., Waldvogel, M., Futo, E., Hasler, H., Binz, K., Guler, H.P., Schimid, C. and Froesch, E.R. (1989) Recombinant human insulin-like growth factor I induces its own specific carrier protein in hypophysectomized and diabetic rats.Proc. Natl Acad. Sci. USA 86, 3813–7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Animal Science, School of Veterinary Medicine, University of California-Davis, Meyer Hall, 95616, Davis, CA, USA

    Jesse C. Chow, James D. Murray, Daniel Pomp, Ransom L. Baldwin, Christopher C. Calvert & Anita M. Oberbauer

  2. Department of Reproduction, School of Veterinary Medicine, University of California-Davis, Meyer Hall, 95616, Davis, CA, USA

    James D. Murray

  3. Oklahoma State University, Stillwater, OK, USA

    Daniel Pomp

Authors
  1. Jesse C. Chow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James D. Murray
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Pomp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ransom L. Baldwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher C. Calvert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anita M. Oberbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chow, J.C., Murray, J.D., Pomp, D. et al. Regulation of insulin-like growth factor-l and binding protein-3 expression in oMtla-oGH transgenic mice. Transgenic Research 3, 127–133 (1994). https://doi.org/10.1007/BF01974091

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01974091

Keywords

Search

Navigation