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.
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.
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
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.
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.
Baxter, R.C., Zaltsman, Z. and Turtle, J.R. (1982) Induction of somatogenic receptors in livers of hypersomatotropic, rats.Endocrinol. 111, 1020–32.
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.
Borst, D.W. and Sayare, M. (1982) Photoactivated cross-linking of prolactin to hepatic membrane binding sites.Biochem. Biophys. Res. Comm. 105, 194–201.
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.
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.
Dellacha, J.M. and Sonenberg, M. (1964) Purification of bovine growth hormone.J. Biol. Chem. 239, 1515–20.
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.
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.
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.
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.
Hartree, A.S., Kovacic, N. and Thomas, M. (1965) Growth-promoting and luteotrophic activities of human growth hormone.J. Endocrinol. 33, 249–58.
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.
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.
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.
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.
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.
Knobil, E. and Hotchkiss, J. (1964) Growth hormone.Ann. Rev. Physiol. 26, 47–74.
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
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.
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.
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.
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.
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.
Nordstedt, G. and Palmiter, R. (1984) Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver.Cell 36, 805–12.
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.
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.
Picard, F. and Postel-Vinay, M.C. (1984) Hypophysectomy and growth hormone receptors in liver membranes of male rats.Endocrinol. 114, 1328–33.
Posner, B.I. (1976) Characterization and modulation of growth hormone and prolactin binding in mouse liver.Endocrinol. 98, 645–54.
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.
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.
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.
Scatchard, G.A. (1949) The attractions of proteins for small molecules and ions.Ann. N. Y. Acad. Sci. 51, 660–6.
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.
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.
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.
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.
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02524752