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Identification and characterization of glucocorticoid receptors in liver of nude mice

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Glucocorticoids regulate the expression of many liver-specific genes via glucocorticoid receptors. The presence of glucocorticoid receptors in liver has been reported in many mammalian species but not in nude mice. In the present study, we demonstrate the presence of specific glucocorticoid receptors in nude mouse liver. The binding of ligands to these receptors could be completely inhibited by RU486, and partially blocked by hydrocortisone and progesterone, whereas estrogen and testosterone had no effect. Hydrocortisone down-regulated the level of glucocorticoid receptors in livers of nude mice and correspondingly enhanced the activities of tyrosine aminotransferase and γ-glutamyltransferase. Our results indicate that glucocorticoid receptors in nude mouse liver are specific, fully functional, and present at levels 28.5-fold higher than in the liver of normal inbred mice. We suggest that the nude mouse is a valuable model for studies of hepatic glucocorticoid action and may provide a clue to a putative hepatic-thymic interaction.

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References

  1. Champion S, Imhof BA, Savagner P, Thiery JP. The embryonic thymus produces chemotactic peptides involved in the homing of hemopoietic precursors. Cell 44:781–790;1986.

    Article  PubMed  Google Scholar 

  2. Cordier AC, Haumont SM. Development of thymus, parathyroids, and ultimo-branchial bodies in NMRI and nude mice. Am J Anat 157:227–263;1980.

    Article  PubMed  Google Scholar 

  3. Das HR, Lavin M, Sicuso A, Young DV. The uncoupling of macromolecular synthesis from cell division in SV3T3 cells by glucocorticoids: The imposition of a G2 block. J Cell Physiol 117:241–248;1983.

    Article  PubMed  Google Scholar 

  4. Diamondstone TI. Assay of tyrosine transaminase activity by conversion ofp-hydroxyphenylpyruvate top-hydroxybenzaldehyde. Anal Biochem 16:395–401;1966.

    Article  Google Scholar 

  5. Feldman D. Ontology of rat hepatic glucocorticoid receptors. Endocrinology 95:1219–1227;1974.

    PubMed  Google Scholar 

  6. Goldfeld AE, Firestone GL, Shaw PA, Gluecksohn-Waelsch S. Recessive lethal deletion on mouse chromosome 7 affects glucocorticoid receptor binding activities. Proc Natl Acad Sci USA 80:1431–1434;1983.

    PubMed  Google Scholar 

  7. Govindan MV, Gronemeyer H. Characterization of the rat liver glucocorticoid receptor purified by DNA-cellulose and ligand affinity chromatography. J Biol Chem 259:12915–12924;1984.

    PubMed  Google Scholar 

  8. Hartree EF. Determination of protein: A modification of the Lowry method that gives a linear photometric response. Anal Biochem 48:422–427;1972.

    Article  PubMed  Google Scholar 

  9. Hers HG. Effects of glucocorticoids on carbohydrate metabolism. Agents Actions 17:248–254;1985.

    Article  Google Scholar 

  10. Huang YS, Das UN, Horrobin DF. Effect of dexamethasone on the distribution of essential fatty acids in plasma and liver phospholipids. IRCS Med Sci 14:180–181;1986.

    Google Scholar 

  11. Iqbal MJ, Wilkinson ML, Johnson PJ, Williams R. Sex steroid receptor proteins in foetal, adult and malignant human liver tissue. Br J Cancer 48:791–796;1983.

    PubMed  Google Scholar 

  12. Kalimi M, Gupta S. Physicochemical characterization of rat liver glucocorticoid receptor during development. J Biol Chem 257:13324–13328;1982.

    PubMed  Google Scholar 

  13. Kitraki E, Alexis N, Stylianopoulou F. Glucocorticoid receptors in developing rat brain and liver. J Steroid Biochem 20:263–269;1984.

    Article  PubMed  Google Scholar 

  14. Lui WY, P'eng FK, Chang TJ, Kao HL, Liu TY, Chi CW. Ischemia effect on the level of steroid hormone receptors in hepatocellular carcinoma and adjacent liver tissue. Eur J Cancer Clin Oncol 25:919–920;1989.

    Article  PubMed  Google Scholar 

  15. Lustenberger P, Blanchardie P, Denis M, Formstecher P, Orsonneau JL, Bernard S. Nontransformed rabbit liver glucocorticoid receptor: Purification, characterization and transformation. Biochimie 67:1267–1278;1985.

    PubMed  Google Scholar 

  16. Marks AR, Moore DD, Buckley DI, Gametchu B, Goodman HM. Conservation of the DNA binding domain and other properties between porcine and rat glucocorticoid receptors. J Steroid Biochem 24:1097–1103;1986.

    Article  PubMed  Google Scholar 

  17. Nagasue N, Ito A, Yukaya H, Ogawa Y. Androgen receptors in hepatocellular carcinoma and surrounding parenchyma. Gastroenterology 89:643–647;1985.

    PubMed  Google Scholar 

  18. Nagasue N, Ito A, Yukaya H, Ogawa Y. Estrogen receptors in hepatocellular carcinoma. Cancer 57:87–91;1986.

    PubMed  Google Scholar 

  19. Nakabayashi H, Watanabe K, Saito A, Otsuru A, Sawadaishi K, Tamaoki T. Transcriptional regulation of alpha-fetoprotein expression by dexamethasone in human hepatoma cells. J Biol Chem 264;266–271;1989.

    PubMed  Google Scholar 

  20. Nawa K, Nakamura T, Kumatori A, Noda C, Ichihara A. Glucocorticoid-dependent expression of the albumin gene in adult rat hepatocytes. J Biol Chem 261:16883–16888;1986.

    PubMed  Google Scholar 

  21. Oakley RH, Cidlowski JA. Homologous down regulation of the glucocorticoid receptor: The molecular machinery. Crit Rev Euk Gene Express 3:63–88;1993.

    Google Scholar 

  22. Ohnishi S, Murakami T, Moriyama T, Mitamura K, Imawari M. Androgen and estrogen receptors in hepatocellular carcinoma and in the surrounding noncancerous liver tissue. Hepatology 6:440–443;1986.

    PubMed  Google Scholar 

  23. P'eng FK, Lui WY, Chang TJ, Kao HL, Wu LH, Liu TY, Chi CW. Glucocorticoid receptors in hepatocellular carcinoma and adjacent liver tissue. Cancer 62:2134–2138;1988.

    PubMed  Google Scholar 

  24. P'eng FK, Lui WY, Wu LH, Chi CW, Kao HL, Chang TJ, Uen YH, Liu M, Chou CK. Levels of steroid hormone receptors in human normal liver, hepatocellular carcinoma and human hepatoma cell lines. J Surg Assoc ROC 18:332–342;1984.

    Google Scholar 

  25. Pepin MC, Pothier F, Barden N. Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene. Nature 355:725–728;1992.

    Article  PubMed  Google Scholar 

  26. Princen HMG, Moshage HJ, Haard HJW, Van Gomert PTL, Yap SH. The influence of glucocorticoid on the fibrinogen messenger RNA content of rat liver in vivo and in hepatocyte suspension culture. Biochem J 220:631–637;1984.

    PubMed  Google Scholar 

  27. Pyke KW, Bach JF. The in vitro migration of murine fetal liver cells to thymic rudiments. Eur J Immunol 9:317–323;1979.

    PubMed  Google Scholar 

  28. Scatchard G. The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672;1949.

    Google Scholar 

  29. Schulz WA, Gebhardt R, Mecke D. Dexamethasone restores normal inducibility of ornithine decarboxylase in primary cultures of rat hepatocytes. Eur J Biochem 146:549–553;1985.

    Article  PubMed  Google Scholar 

  30. Stevenson D, Lin JH, Tong MJ, Marshall J. Characteristics of a cell line (Tong/HCC) established from a human hepatocellular carcinoma. Hepatology 7:1291–1295;1987.

    PubMed  Google Scholar 

  31. Sunahara GI, Chiesa A. Phorone (diisopropylidene acetone), a glutathione depleter, decreases rat glucocorticoid receptor binding in vivo. Carcinogenesis 13:1083–1089;1992.

    PubMed  Google Scholar 

  32. Svec F, Rudis M. Glucocorticoids regulate the glucocorticoid receptor in the AtT-20 cell. J Biol Chem 256:5984–5987;1981.

    PubMed  Google Scholar 

  33. Vedeckis WV. Limited proteolysis of the mouse liver glucocorticoid receptor. Biochemistry 22:1975–1983;1983.

    Article  PubMed  Google Scholar 

  34. Wringhton SA, Schuetz EG, Watkins PB, Maurel P, Barwick J, Bailey BS, Hartle HT, Young B, Guzelian P. Demonstration in multiple species of inducible hepatic cytochrome P-450 and their messenger RNAs related to the glucocorticoid-inducible cytochrome P-450 of the rat. Mol Pharmacol 28:312–321;1985.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Research, Veterans General Hospital-Taipei, Shih-Pai, 11217, Taipei, Taiwan (Republic of China)

    Chin-Wen Chi, Tsung-Yun Liu, Su-Hua Chiang, Su-Ling Cheng, Ching-Yuang Lin & Chi-Kuan Ho

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  1. Chin-Wen Chi
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Chi, CW., Liu, TY., Chiang, SH. et al. Identification and characterization of glucocorticoid receptors in liver of nude mice. J Biomed Sci 1, 224–228 (1994). https://doi.org/10.1007/BF02253306

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  • DOI: https://doi.org/10.1007/BF02253306

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