Skip to main content
Log in

Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes

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

Abstract

The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated, by the use, of labelled ovine prolactin) was increased 2–3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aguilar, R.C., Fernandez, H.N., Dellacha, J.M., Calandra, R.S., Bartke, A. and Turyn, D. (1992) Identification of somatogenic binding sites in liver microsomes from normal mice and transgenic mice expressing human growth hormone gene.Life Sci. 50, 615–20.

    Article  PubMed  CAS  Google Scholar 

  • Amit, T., Barkey, R.J., Gavish, M. and Youdim, M.B.H. (1984) Induction of prolactin (PRL) receptors by PRL in the rat lung and liver. Demonstration and characterization of a soluble receptor.Endocrinol. 114, 545–52

    CAS  Google Scholar 

  • Bartke, A., Steger, R.W., Hodges, S.L., Parkening, T.A., Collins, T.J., Yun, J.S. and Wagner, T.E. (1988) Infertility in transgenic female mice with human growth hormone expression: evidence for luteal failure.J. Exp. Zool. 248, 212–4.

    Article  Google Scholar 

  • Baxter, R.C. and Zaltsman, Z. (1984). Induction of hepatic receptors for growth hormone (GH) and prolactin by GH infusion is sex independent.Endocrinol. 115, 2003–14.

    Google Scholar 

  • Baxter, R.C., Zaltsman, Z. and Turtle, J.R. (1982) Induction of somatogenic receptors in livers of hypersomatotropic, rats.Endocrinol. 111, 1020–32.

    CAS  Google Scholar 

  • Baxter, R.C., Zaltsman, Z. and Turtle, J.R. (1984) Rat growth hormone (GH) but not prolactin (PRL) induces both GH and PRL receptors in female rat liver.Endocrinol. 114, 1893–901.

    CAS  Google Scholar 

  • Borst, D.W. and Sayare, M. (1982) Photoactivated cross-linking of prolactin to hepatic membrane binding sites.Biochem. Biophys. Res. Comm. 105, 194–201.

    Article  PubMed  CAS  Google Scholar 

  • Chen, W.Y., White, M.E., Wagner, T.E. and Kopchick, J.J. (1991) Punctional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice.Endocrinol. 129, 1402–8.

    CAS  Google Scholar 

  • Dave, J.R., Richardson, L.L. and Knazek, R.A. (1983) Prolactinbinding capacity, prostaglandin synthesis and fluidity of murine hepatic membranes are modified during pregnancy and lactation.J. Endocrinol. 99, 99–106.

    PubMed  CAS  Google Scholar 

  • Dellacha, J.M. and Sonenberg, M. (1964) Purification of bovine growth hormone.J. Biol. Chem. 239, 1515–20.

    PubMed  CAS  Google Scholar 

  • Forsyth, I.A., Folley, S.J. and Chadwick, A. (1965) Lactogenic and pigeon crop-stimulating activities of human pituitary growth hormone preparation.J. Endocrinol. 31, 115–26.

    PubMed  CAS  Google Scholar 

  • Furuhashi, N. and Fang, V.S. (1978) Hormone receptors in livers of GH3 tumor-bearing rats: the predominant effect of growth hormone and testosterone.Endocrinol. 103, 2053–60.

    CAS  Google Scholar 

  • Ginsberg, B.H. (1977) The insulin receptor: properties and regulation. In Litwac, G. ed.,Biochemical Actions of Hormones, Vol. IV, Chapter 7, New York: Academic Press.

    Google Scholar 

  • Hammer, R.E., Brinster, R.L. and Palmiter, R.D. (1985) Use of gene transfer to increase animal growth.Cold Spring Harbor Symp. Quant. Biol. 50, 379–87.

    PubMed  CAS  Google Scholar 

  • Hartree, A.S., Kovacic, N. and Thomas, M. (1965) Growth-promoting and luteotrophic activities of human growth hormone.J. Endocrinol. 33, 249–58.

    PubMed  CAS  Google Scholar 

  • Herington, A.C., Phillips, L.S. and Daughaday, W.J. (1976a) Pituitary regulation of human growth hormone binding sites in rat liver membranes.Metabolism 25, 341–53.

    Article  PubMed  CAS  Google Scholar 

  • Herington, A.C., Veith, N.M. and Burber, H.C. (1976b) Characterization of the binding of human growth hormone to microsomal membranes from rat liver.Biochem. J. 158, 61–9.

    PubMed  CAS  Google Scholar 

  • Herington, A.C., Harrison, D. and Graystone, J. (1983) Hepatic binding of human and bovine growth hormones and ovine prolactin in the dwarf ‘little’ mouse.Endocrinol. 112, 2032–8.

    Article  CAS  Google Scholar 

  • Husman, B., Nordstedt, G., Mode, A. and Gustafsson, J.-A. (1985) The mode of growth hormone administration is of major importance for the excretion of the major male rat urinary proteins.Mol. Cell. Endocrinol. 40, 205–10.

    Article  PubMed  CAS  Google Scholar 

  • Knazek, R.A., Lui, S.C., Graeter, R.L., Wright, P.C., Mayer, J.R., Lewis, R.H., Gould, E.B. and Keller, J.A. (1978) Growth hormone causes rapid induction of lactogenic receptor activity in the Snell dwarf mouse liver.Endocrinol. 103, 1590–6.

    CAS  Google Scholar 

  • Knobil, E. and Hotchkiss, J. (1964) Growth hormone.Ann. Rev. Physiol. 26, 47–74.

    Article  CAS  Google Scholar 

  • Maiter, D., Underwood, L.E., Maes, M., Davenport, M.L. and Ketelslegers, J.M. (1988) Different effects of intermittent and continuous growth hormone (GH) administration on serum somatomedin-C/insulin-like growth factor I and liver GH receptors in hypophysectomized rats.Endocrinol. 123, 1053–9

    CAS  Google Scholar 

  • Mattera, R., Turyn, D., Fernández, H.N. and Dellacha, J.M. (1981) Structural characterization of iodinated bovine growth hormone.Int. Pep. Protein Res. 19, 172–80.

    Article  Google Scholar 

  • Mayerhofer, A., Weis, J., Bartke, A., Yun, J.S. and Wagner, T.E. (1990) Effects of transgenes for human and bovine growth hormones on age-related changes in ovarian morphology in mice.Anat. Rec. 227, 175–86.

    Article  PubMed  CAS  Google Scholar 

  • McGrane, M.M., deVente, J., Yun, J., Bloom, J., Park, E., Wynshaw, A., Wagner, T., Rottman, F.M. and Hanson, R.W. (1988) Tissue-specific expression and dietary regulation of a chimeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice.J. Biol. Chem. 263, 11443–51.

    PubMed  CAS  Google Scholar 

  • Mills, J.B., Ashworth, R.B., Wilhelmi, A.E. and Hartree, A.S. (1969) Improved method for the extraction and purification of human growth hormone.J. Clin. Endocrinol. Metabol. 29, 1456–9.

    CAS  Google Scholar 

  • Mode, A., Wiersma-Larsson, E., Ström, A., Zaphiropoulos, P.G. and Gustaffson, J.-A. (1989) A dual role of growth hormone as a feminizing and masculinizing factor in the control of sex-specific cytochrome P-450 isozymes in rat liver.J. Endocrinol. 120, 311–7.

    PubMed  CAS  Google Scholar 

  • Nordstedt, G. and Palmiter, R. (1984) Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver.Cell 36, 805–12.

    Article  Google Scholar 

  • Nordstedt, G., Mode, A., Eneroth, P. and Gustafsson, J.-A. (1981) Induction of prolactin receptors in rat liver after the administration of growth hormone.Endocrinology 108, 1855–61.

    Google Scholar 

  • Orian, J.M., Snibson, K., Stevenson, J.L., Brandon, M.R. and Herington, A.C. (1991) Elevation of growth hormone (GH) and prolactin receptors in transgenic mice expressing ovine GH.Endocrinol. 128, 1238–46.

    CAS  Google Scholar 

  • Picard, F. and Postel-Vinay, M.C. (1984) Hypophysectomy and growth hormone receptors in liver membranes of male rats.Endocrinol. 114, 1328–33.

    Article  CAS  Google Scholar 

  • Posner, B.I. (1976) Characterization and modulation of growth hormone and prolactin binding in mouse liver.Endocrinol. 98, 645–54.

    CAS  Google Scholar 

  • Posner, B.I., Kelly, P.A., Shiu, R.P.C., Paud, R. and Friesen, H.G. (1974) Studies of insulin, growth hormone and prolactin binding: tissue distribution, species variation and characterization.Endocrinol. 95, 521–31.

    Article  CAS  Google Scholar 

  • Ranke, M.B., Stanley, C.A., Rodbard, D., Baker, L., Bongiovanni, A. and Parks, J.S. (1976) Sex differences in binding of human growth hormone to isolated rat hepatocytes.Proc. Natl Acad. Sci. USA,73, 847–51.

    Article  PubMed  CAS  Google Scholar 

  • Sanches-Jimenez, F., Fielder, P.J., Martinez, R.R., Smith, W.C. and Talamantes, F. (1990) Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptors and serum binding protein in the mouse.Endocrinol. 126, 1270–5.

    Google Scholar 

  • Scatchard, G.A. (1949) The attractions of proteins for small molecules and ions.Ann. N. Y. Acad. Sci. 51, 660–6.

    CAS  Google Scholar 

  • Selden, R.F., Yun, J.S., Moore, D.D., Rowe, M.E., Malia, M.A., Wagner, T.E. and Goodman, H.M. (1989) Glucocorticoid regulation of human growth hormone expression in transgenic mice and transiently transfected cells.J. Endocrinol. 122, 49–60.

    Article  PubMed  CAS  Google Scholar 

  • Tannenbaum, G.S. and Martin, J.B. (1976) Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat.Endocrinol. 98, 562–70.

    CAS  Google Scholar 

  • Vergani, G. and Mayerhofer, A. (1991) Acute effects of human growth hormone on liver cellsin vitro: a comparison with livers of mice transgenic for human growth hormone.Tissue and Cell 23, 607–12.

    Article  PubMed  CAS  Google Scholar 

  • Wagner, T.E., Hoppe, P.C., Jollick, J.D., Scholl, D.R., Hodinka, R.L. and Gault, J.B. (1981) Microinjection of a rabbit β-globin gene into zygotes and its subsequent expression in adult mice and their offspring.Proc. Natl Acad. Sci. USA 78, 6376–80.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aguilar, R.C., Fernandez, H.N., Dellacha, J.M. et al. Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes. Transgenic Research 1, 221–227 (1992). https://doi.org/10.1007/BF02524752

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02524752

Keywords

Navigation