Androgen Regulation of Gene Expression: Studies of Ornithine Decarboxylase in Murine Kidney

  • Olli A. Janne
  • Noreen J. Hickok
  • Mervi Julkunen
  • Anne Crozat
  • Leonard Eisenberg
  • Evie Melanitou
Part of the Serono Symposia, USA book series (SERONOSYMP)


The action of androgenic steroids in their target tissues occurs in a receptor-mediated fashion similar to that of other steroid hormones. The details of steroid hormone action, as they are currently known, originate mainly from studies of glucocorticoids, estrogens, and progestins, despite the fact that the first and most convincing biological arguments for the importance of soluble receptors in the expression of steroid action are from studies of androgen resistance syndromes (1–3). There are several possible reasons that research on androgen action has lagged behind that of female sex steroids and glucocorticoids. These include problems in the measurement and purification of the androgen receptor; a relatively slow progress in isolation and characterization of androgen-responsive genes and their encoded products; and paucity of suitable experimental systems to study androgen action in cultured cells. Over the last several years, however, a number of gene products regulated by androgens have been characterized and their induction kinetics in vivo elucidated. The best defined of these genes/gene products fall, with regard to their tissues of expression, into three main categories: (i) α2u -globulin and the major urinary protein (MUP) genes are regulated by androgens in rodent liver (4–11); (ii) prostatein and seminal vesicle basic protein genes are controlled by androgens in rat accessory sex organs (12–19), and (iii) ornithine decarboxylase (ODC), β-glucuronidase, RP2, and kidney androgen-regulated protein (KAP) genes exhibit androgen regulation in murine kidney (20–31).


Androgen Receptor Ornithine Decarboxylase Mouse Kidney Major Urinary Protein Murine Kidney 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bardin CW, Catterall JF. Testosterone, a major determinant of extragenital sexual dimorphism. Science 1981; 211: 1285–94.PubMedCrossRefGoogle Scholar
  2. 2.
    Griffin JE, Leshin M, Wilson JD. Androgen resistance,syndromes. Am J Physiol 1982; 243: E81–7.PubMedGoogle Scholar
  3. 3.
    Kontula KK, Janne OA, Bardin CW. Intracellular hormone receptor defects and disease. In: Conn PM, ed. Receptors IV. Orlando: Academic Press, 1986: 37–74.Google Scholar
  4. 4.
    Roy AK, Chatterjee B, Prasad MSK, Unakar NJ. Role of insulin in the regulation of the hepatic messenger RNA for a2u-globulin in diabetic rats. J Biol Chem 1980; 255: 11614–8.PubMedGoogle Scholar
  5. 5.
    Nakhasi HL, Lynch KR, Dolan KP, Unterman R, Antakly T, Feigelson P. Modification in a2u-globulin gene structure, transcription, and mRNA translation in hepatomas. J Biol Chem 1982; 257: 2726–9.PubMedGoogle Scholar
  6. 6.
    Roy AK, Nath TS, Matwani NM, Chatterjee B. Age-dependent regulation of the polymorphic forms of n2u-globulin. J Biol Chem 1983; 258: 10123–7.PubMedGoogle Scholar
  7. 7.
    Kulkarni AB, Gubito RM, Feigelson P. Developmental and hormonal regulation of a2u-globulin gene transcription. Proc Natl Acad Sci USA 1985; 82:2579–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Derman E. Isolation of a cDNA clone for mouse urinary proteins: age-and sex-related expression of mouse urinary protein genes is transcriptionally controlled. Proc Natl Acad Sci USA 1981; 78; 5425–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Kuhn NJ, Woodworth-Gutai M, Gross KW, Held WA. Subfamilies of the major mouse urinary protein (MUP) multi-gene family: sequence analysis of cDNA clones and differential regulation in the liver. Nucleic Acids Res 1984; 12: 6073–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Clark AJ, Hickman J, Bishop J. A 45-kb DNA domain with two divergently orientated genes is the unit of organisation of the murine major urinary protein genes. EMBO J 1984; 3: 2055–64.PubMedGoogle Scholar
  11. 11.
    Hastie ND, Held WA, Toole JJ. Multiple genes coding for the androgen-regulated major urinary proteins of the mouse. Cell 1979; 17: 749–57.CrossRefGoogle Scholar
  12. 12.
    Parker MG, White R, Williams JG. Cloning and characterization of androgen-dependent mRNA from rat ventral prostate. J Biol Chem 1980; 255: 6996–7001.PubMedGoogle Scholar
  13. 13.
    Page MJ, Parker MG. Effect of androgen on the transcription of rat prostatic binding protein genes. Mol Cell Endocrinol 1982; 27: 343–55.PubMedCrossRefGoogle Scholar
  14. 14.
    Viskochil DH, Perry ST, Lea OA, Stafford DW, Wilson EM, French FS. Isolation of two genomic sequences encoding the Mr=14,000 subunit of rat prostatein. J Biol Chem 1983; 258: 8861–6.PubMedGoogle Scholar
  15. 15.
    Parker M, Hurst H, Page M. Organization and expression of prostatic steroid binding protein genes. J Steroid Biochem 1984; 20: 67–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Kistler MK, Taylor RE Jr, Kandala JC, Kistler WS. Isolation of recombinant plasmids containing structural gene sequences for rat seminal vesicle secretory proteins IV and V. Biochem Biophys Res Commun 1981; 99: 1161–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Kandala JC, Kistler WS, Kistler MK. Methylation of the rat seminal vesicle secretory protein IV gene. Extensive demethylation occurs in several male sex accessory glands. J Biol Chem 1985; 260: 15959–64.PubMedGoogle Scholar
  18. 18.
    Harris SE, Mansson P-E, Tully DB, Burkhart B. Seminal vesicle secretion IV gene: allelic differences due to a series of 20-basepair direct tandem repeats within an intron. Proc Natl Acad Sci USA 1983; 80: 6460–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Fawell SE, McDonald CJ, Higgins SJ. Comparison of seminal vesicle secretory proteins of rodents using antibody and nucleotide probes. Mol Cell Endocrinol 1987; 50: 107–14.PubMedCrossRefGoogle Scholar
  20. 20.
    Kontula KK, Torkkeli TK, Bardin CW, Janne OA. Androgen induction of ornithine decarboxylase mRNA in mouse kidney as studied by complementary DNA. Proc Natl Acad Sci USA 1984; 81: 731–5.PubMedCrossRefGoogle Scholar
  21. 21.
    McConlogue L, Gupta M, Wu L, Coffino P. Molecular cloning and expression of the mouse ornithine decarboxylase gene. Proc Natl Acad Sci USA 1984; 81: 540–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Berger FG, Szymanski P, Read E, Watson G. Androgen regulated ornithine decarboxylase mRNAs of mouse kidney. J Biol Chem 1984; 259: 7941–6.PubMedGoogle Scholar
  23. 23.
    Hickok NJ, Seppanen PJ, Kontula KK, Janne PA, Bardin CW, Janne OA. Two ornithine decarboxylase mRNA species in mouse kidney arise from size heterogeneity at their 3’ termini. Proc Natl Acad Sci USA 1986; 83: 594–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Swank RT, Paigan K, Davey R, Chapman V, Labarca C, Watson G, Ganschow R, Brandt EJ, Novak E. Genetic regulation of mammalian glucuronidase. Recent Prog Horm Res 1978; 34: 401–36.PubMedGoogle Scholar
  25. 25.
    Palmer R, Gallagher PM, Boyko WL, Ganschow RE. Genetic control of levels of murine kidney glucuronidase mRNA in response to androgen. Proc Natl Acad Sci USA 1983; 80: 7596–600.PubMedCrossRefGoogle Scholar
  26. 26.
    Catterall JF, Leary SL. Detection of early changes in androgen-induced mouse renal 8-glucuronidase mRNA using cloned cDNA. Biochemistry 1983; 22: 6049–53.PubMedCrossRefGoogle Scholar
  27. 27.
    Watson CS, Catterall JF. Genetic regulation of androgen-induced accumulation of mouse renal 8-glucuronidase mRNA. Endocrinology 1986; 118: 1081–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Berger FG, Gross KW, Watson G. Isolation and characterization of a DNA sequence complementary to an androgen-inducible messenger RNA from mouse kidney. J Biol Chem 1981; 256: 7006–13.PubMedGoogle Scholar
  29. 29.
    Elliott RW, Berger FG. DNA sequence polymorphism in an androgen-regulated gene is associated with alteration in the encoded RNAs. Proc Natl Acad Sci USA 1983; 80: 501–4.PubMedCrossRefGoogle Scholar
  30. 30.
    King D, Snider LD, Lingrel JB. Polymorphism in an androgen-regulated mouse gene is the result of the insertion of B1 repetitive element into the transcription unit. Mol Cell Biol 1986; 6: 209–17.PubMedGoogle Scholar
  31. 31.
    Watson CS, Salomon D, Catterall JF. Structure and expression of androgen-regulated genes in mouse kidney. Ann NY Acad Sci 1984; 438: 101–14.PubMedCrossRefGoogle Scholar
  32. 32.
    Catterall JF, Kontula KK, Watson CS, Seppanen PJ, Funkenstein B, Melanitou E, Hickok NJ, Bardin CW, Janne OA. Regulation of gene expression by androgens in murine kidney. Recent Prog Horm Res 1986; 42: 71–109.PubMedGoogle Scholar
  33. 33.
    Pegg AE, McCann PP. Polyamine metabolism and function. Am J Physiol 1982; 243: C212–21.PubMedGoogle Scholar
  34. 34.
    Steglich C, Scheffler IE. An ornithine decarboxylase-deficient mutant of Chinese hamster ovary cells. J Biol Chem 1982; 257: 4603–9.PubMedGoogle Scholar
  35. 35.
    Pohjanpelto P, Holtta E, Janne OA. Mutant strain of Chinese hamster ovary cells with no detectable ornithine decarboxylase activity. Mol Cell Biol 1985; 5: 1385–90.PubMedGoogle Scholar
  36. 36.
    Janne J, Poso H, Raina A. Polyamines in rapid growth and cancer. Biochim Biophys Acta 1978; 473: 241–93.PubMedGoogle Scholar
  37. 37.
    Seely JE, Poso H, Pegg AE. Purification of ornithine decarboxylase from kidneys of androgen treated mice. Biochemistry 1982; 21: 3394–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Isomaa VV, Pajunen AEI, Bardin CW, Janne OA. Ornithine decarboxylase in mouse kidney. Purification, characterization and radioimmunological determination of the enzyme protein. J Biol Chem 1983; 258: 6735–40.PubMedGoogle Scholar
  39. 39.
    Hickok NJ, Seppanen PJ, Gunsalus GL, Janne OA. Complete amino acid sequence of human ornithine decarboxylase deduced from complementary DNA. DNA 1987; 6: 179–87.PubMedCrossRefGoogle Scholar
  40. 40.
    Gupta M, Coffino P. Mouse ornithine decarboxylase. Complete amino acid sequence deduced from cDNA. J Biol Chem 1985; 260: 2941–4.PubMedGoogle Scholar
  41. 41.
    Janne OA, Kontula KK, Isomaa VV, Torkkeli TK, Bardin CW. Androgen receptor-dependent regulation of ornithine decarboxylase gene expression in mouse kidney. In: Eriksson H, Gustafsson J-A, eds. Steroid hormone receptors: structure and function. Amsterdam: Elsevier Science Publishers BV, 1983: 461–76.Google Scholar
  42. 42.
    Persson L, Seely JE, Pegg AE. Investigation of structure and rate of synthesis of ornithine decarboxylase protein in mouse kidney. Biochemistry 1984; 23: 3777–83.PubMedCrossRefGoogle Scholar
  43. 43.
    Pulkka A, Taskinen T, Aaltonen H, Ramberg J, Pajunen AEI. Studies on the degradation of ornithine decarboxylase by the immunoblotting technique. Biochem Int 1985; 11: 845–51.PubMedGoogle Scholar
  44. 44.
    Macrae M, Coffino P. Complementation of a polyamine-deficient Escherichia coli mutant by expression of mouse ornithine decarboxylase. Mol Cell Biol 1987; 7: 564–7.PubMedGoogle Scholar
  45. 45.
    Seely JE, Pegg AE. Changes in mouse kidney ornithine decarboxylase activity are brought about by changes in the amount of enzyme protein as measured by radioimmunoassay. J Biol Chem 1983; 258: 2496–500.PubMedGoogle Scholar
  46. 46.
    Rogers S, Wells R, Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 1986; 234: 364–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Tabor CW, Tabor H. Polyamines. Annu Rev Biochem 1984; 53: 749–90.CrossRefGoogle Scholar
  48. 48.
    Kahana C, Nathans D. Translational regulation of mammalian ornithine decarboxylase by polyamines. J Biol Chem 1985; 260: 15390–3.PubMedGoogle Scholar
  49. 49.
    Holtta E, Pohjanpelto P. Control of ornithine decarboxylase in Chinese hamster ovary cells by polyamines. Translational inhibition of synthesis and acceleration of degradation of the enzyme by putrescine, spermidine, and spermine. J Biol Chem 1986; 261: 9502–8.PubMedGoogle Scholar
  50. 50.
    Pajunen AEI, Isomaa VV, Janne OA, Bardin CW. Androgenic regulation of ornithine decarboxylase activity and its relationship to changes in cytosol and nuclear androgen receptor concentrations. J Biol Chem 1982; 257: 8190–8.PubMedGoogle Scholar
  51. 51.
    Sertich GJ, Pegg AE. Polyamine administration reduces ornithine decarboxylase activity without affecting the mRNA content. Biochem Biophys Res Commun 1987; 143: 424–30.PubMedCrossRefGoogle Scholar
  52. 52.
    Kahana C, Nathans D. Nucleotide sequence of murine ornithine decarboxylase mRNA. Proc Natl Acad Sci USA 1985; 82: 1673–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Winqvist R, Makela TP, Seppanen P, Janne OA, Alhonen-Hongisto L, Janne J, Grzeschik K-H, Alitalo K. Human ornithine decarboxylase sequences map to chromosome regions 2pter-p23 and 7cen-qter but are not co-amplified with the NMYC oncogene. Cytogenet Cell Genet 1986; 42: 133–40.PubMedCrossRefGoogle Scholar
  54. 54.
    Janne OA, Kontula KK, Isomaa VV, Bardin CW. Ornithine decarboxylase mRNA in mouse kidney: a low abundancy gene product regulated by androgens with rapid kinetics. Ann NY Acad Sci 1984; 438: 72–84.PubMedCrossRefGoogle Scholar
  55. 55.
    Berger FG, Loose D, Meisner H, Watson G. Androgen induction of messenger RNA concentrations in mouse kidney is posttranscriptional. Biochemistry 1986; 25: 1170–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Brock ML, Shapiro DJ. Estrogen stabilizes vitellogenin mRNA against cytoplasmic degradation. Cell 1983; 34: 207–14.PubMedCrossRefGoogle Scholar
  57. 57.
    Brock ML, Shapiro DJ. Estrogen regulates the absolute rate of transcription of the Xenopus levis vitellogenin genes. J Biol Chem 1983; 258: 5449–55.PubMedGoogle Scholar
  58. 58.
    Vannice JL, Taylor JM, Ringold GM. Glucocorticoid-mediated induction of a1-acid glycoprotein: evidence for hormone-regulated RNA processing. Proc Natl Acad Sci USA 1984; 81: 4241–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Paek I, Axel R. Glucocorticoids enhance stability of human growth hormone mRNA. Mol Cell Biol 1987; 7: 1496–1507.PubMedGoogle Scholar
  60. 60.
    Field LJ, Gross KW. Ren-1 and Ren-2 loci are expressed in mouse kidney. Proc Natl Acad Sci USA 1985; 82: 6196–200.PubMedCrossRefGoogle Scholar
  61. 61.
    Bishop JO, Clark AJ, Clissold PM, Hainy S, Franke V. Two main groups of mouse major urinary protein genes, both largely located on chromosome 4. EMBO J 1982; 1: 615–20.PubMedGoogle Scholar
  62. 62.
    Melanitou E, Cohn DA, Bardin CW, Janne OA. Genetic variation in androgen regulation of ornithine decarboxylase gene expression in inbred strains of mice. Mol Endocrinol 1987; 1: 266–73.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Olli A. Janne
    • 1
  • Noreen J. Hickok
    • 1
  • Mervi Julkunen
    • 1
  • Anne Crozat
    • 1
  • Leonard Eisenberg
    • 1
  • Evie Melanitou
    • 1
  1. 1.The Population Council and The Rockefeller UniversityNew YorkUSA

Personalised recommendations