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Sexual Differentiating Actions of Steroids on the Hypothalamopituitary-Liver Axis

  • Jan-Åke Gustafsson
  • Peter Eneroth
  • Barbro Haglund
  • Tomas Hökfelt
  • Agneta Mode
  • Paul Skett
  • Örjan Wrange
Part of the Published Nobel Symposia book series (NOFS, volume 42)

Abstract

In 1953, Hübener and Amelung (1) showed a sex-related difference of hepatic corticosteroid metabolism in the rat. This finding was substantially confirmed by subsequent reports using corticosteroids (2–4), androgens (3–5) and estrogens (5) as substrates. Male animals show a higher hydroxylating activity than females (4,5) whereas females exhibit a higher 5a-reductase activity (3). In 1958, Yates et al. (3) published the first study indicating that androgens were involved in the control of steroid metabolism in rat liver. It was found that castration increased and testosterone treatment decreased the 5α-reductase activity. This finding was confirmed and extended by DeMoor and Denef (6) and Gustafsson and Stenberg (7–10) who showed the dependence of the adult male pattern of metabolism on the presence of neonatal androgen (imprinting). The sexual differences in the hepatic metabolism of 4-androstene-3, 17-dione and 5cx-androstane-3a,17β-diol are illustrated in Fig. 1. Although dependent on neonatal androgen exposure, no sex-related differences in steroid metabolism were observed until 30 days of age (11–15).

Keywords

Androgen Receptor Pituitary Gland Hepatic Metabolism Suprachiasmatic Nucleus Preoptic Area 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hübener, H.J. and Amelung, D. (1953) Hoppe-Seyler’s Z. Physiol. Chem. 293, 137–141.CrossRefGoogle Scholar
  2. 2.
    Forchielli, E. and Dorfman, R.I. (1956) J. Biol. Chem. 223, 443–448.PubMedGoogle Scholar
  3. 3.
    Yates, F.E., Herbst, A.L. and Urquhart, J. (1958) Endocrinology 63, 887–902.PubMedCrossRefGoogle Scholar
  4. 4.
    Leybold, K. and Staudinger, H. (1959) Biochem. Z. 331, 389–398.Google Scholar
  5. 5.
    Conney, A.H., Schneidman, K., Jacobson, M. and Kuntzman, R. (1965) Ann. N.Y. Acad. Sci. 123, 98–109.PubMedCrossRefGoogle Scholar
  6. 6.
    DeMoor, P. and Denef, C. (1968) Endocrinology 82, 480–492.PubMedCrossRefGoogle Scholar
  7. 7.
    Einarsson, K., Gustafsson, J.-Å. and Stenberg, Å (1973) J. Biol. Chem. 245, 4987–4997.Google Scholar
  8. 8.
    Begue, R.-J., Gustafsson, J.-Å. and Gustafsson, S. (1973) Eur. J. Biochem. 40, 361–366.PubMedCrossRefGoogle Scholar
  9. 9.
    Gustafsson, J.-Å. and Stenberg, Å. (1974) J. Biol. Chem. 249, 711–718.PubMedGoogle Scholar
  10. 10.
    Gustafsson, J.-Å. and Stenberg, Å. (1974) J. Biol. Chem. 249, 719–723.PubMedGoogle Scholar
  11. 11.
    Björkhem, I., Eriksson, H., Gustafsson, J.-Å., Karlmar, K.-E. and Stenberg, Å. (1972) Eur. J. Biochem. 27, 318–326.PubMedCrossRefGoogle Scholar
  12. 12.
    Berg, A. and Gustafsson, J.-Å. (1973) J. Biol. Chem. 248, 6559–6567.PubMedGoogle Scholar
  13. 13.
    Gustafsson, J.-Å. and Gustafsson, S.A. (1974) Eur. J. Biochem. 44, 225–233.PubMedCrossRefGoogle Scholar
  14. 14.
    Gustafsson, J.-Å. and Ingelman-Sundberg, M. (1974) J. Biol. Chem. 249, 1940–1945.PubMedGoogle Scholar
  15. 15.
    Stenberg, Å. (1976) J. Endocrinol. 68, 265–272.PubMedCrossRefGoogle Scholar
  16. 16.
    Castro, J.A. and Gillette, J.R. (1957) Biochem. Biophys. Res. Comm. 28, 426–430.CrossRefGoogle Scholar
  17. 17.
    Davies, D.S., Gigon, P.L. and Gillette, J.R. (1968) Biochem. Pharmacol. 17, 1865–1872.PubMedCrossRefGoogle Scholar
  18. 18.
    Gram, T.E., Guarino, A.M., Schroeder, D.H. and Gillette, J.R. (1969) Biochem. J. 113, 681–685.PubMedGoogle Scholar
  19. 19.
    El. Defrawy El. Masry, S. Cohen, G.M. and Mannering, G.J. (1974) Drug Metab. Dispos. 2, 267–278.Google Scholar
  20. 20.
    El. Defrawy El Masry, S. and Mannering, G.J. (1974) Drug Metab. Dispos. 2, 279–284.Google Scholar
  21. 21.
    Erickson, R.R. and Holtzman, J.L. (1976) Biochem. Pharmacol. 25, 1501–1506.PubMedCrossRefGoogle Scholar
  22. 22.
    Bill, J.U. and Ecobichon, D.J. (1974) Can. J. Biochem. 53, 433–437.Google Scholar
  23. 23.
    Quinn, G.P., Axelrod, J. and Brodie, B.B. (1958) Biochem. Pharmacol. 1, 152–159.CrossRefGoogle Scholar
  24. 24.
    Gustafsson, J.-Å., Pousette, Å., Stenberg, a. and Wrange, Ö. (1975) Biochemistry 14, 3942–3948.CrossRefGoogle Scholar
  25. 25.
    Feigelson, M. (1973) Enzyme 15, 169–176.PubMedGoogle Scholar
  26. 26.
    Denef, C. (1974) Endocrinology 94, 1577–1582.PubMedCrossRefGoogle Scholar
  27. 27.
    Gustafsson, J.- Å. and Stenberg, Å. (1974) Endocrinology 95, 891–896.PubMedCrossRefGoogle Scholar
  28. 28.
    Flerkö, B. In “The Hypothalamus” Eds. Martini, L., Motta, M. and Fraschini, F. (1970) Academic Press, p. 351–363.Google Scholar
  29. 29.
    Harris, G.W. (1964) Endocrinology 75, 627–648.PubMedCrossRefGoogle Scholar
  30. 30.
    Gustafsson, J.-Å., Ingelman-Sundberg, M., Stenberg, Å. and Hökfelt, T. (1976) Endocrinology 98, 922–926.PubMedCrossRefGoogle Scholar
  31. 31.
    Colby, H.D., Gaskin, J.H. and Kitay, J.I. (1974) Steroids 24, 679–686.PubMedCrossRefGoogle Scholar
  32. 32.
    Kim, S., Wasserman, L., Lew, B. and Ki Paik, W. (1975) FEBS Lett. 51, 164–167.PubMedCrossRefGoogle Scholar
  33. 33.
    Kramer, R.E., Greiner, J.W., Canady, W.J. and Colby, H.D. (1975) Biochem. Pharmacol. 24, 2097–2099.PubMedCrossRefGoogle Scholar
  34. 34.
    Wilson, J.T. and Spelsberg, T.C. (1976) Biochem. J. 154, 433–438.PubMedGoogle Scholar
  35. 35.
    Schillinger, E. and Gerhards, E. (1974) Acta Endocrinol. (Kbh) 77, 502–508.Google Scholar
  36. 36.
    Griffin, E.E. and Miller, L.L. (1974) J. Biol. Chem. 249, 5062–5069.PubMedGoogle Scholar
  37. 37.
    Gustafsson, J.-Å. and Stenberg, Å. (1976) Proc. Natl. Acad. Sci. USA 73, 1462–1465.PubMedCrossRefGoogle Scholar
  38. 38.
    Eneroth, “P., Gustafsson, J.-Å., Skett, P. and Stenberg, Å. (1977) Mol. Cell Endocrinol. 7, 167–175.PubMedCrossRefGoogle Scholar
  39. 39.
    Chen, C.L., Amenomori, Y., Lu, K.H., Voogt, J.L. and Meites, J. (1970) Neuroendocrinology 6, 220–227.PubMedCrossRefGoogle Scholar
  40. 40.
    Lam, P.C.O., Morishige, W.K. and Rothchild, I. (1976) Proc. Soc. Exptl. Biol. Med. 152, 615–617.Google Scholar
  41. 41.
    Arimura, A., Debeljuk, L., Shino, M., Rennels, E.G. and Schally, A.V. (1973) Endocrinology 92, 1507–1514.PubMedCrossRefGoogle Scholar
  42. 42.
    Evans, J.S. (1972) Endocrinology 90, 123–130.PubMedCrossRefGoogle Scholar
  43. 43.
    Gustafsson, J.-Å. and Stenberg, Å. (1975) Acta Endocrinol. (Kbh) 78, 545–553.Google Scholar
  44. 44.
    Gustafsson, J.-Å. and Stenberg, Å. (1975) Endocrinology 96, 501–504.PubMedCrossRefGoogle Scholar
  45. 45.
    Lax, E.R., Ghraf, R., Schriefers, H., Herrmann, M. and Petutschnigk, D. (1976) Acta Endocrinol. (Kbh) 82, 774–784.Google Scholar
  46. 46.
    Kramer, R.E. and Colby, H.D. (1976) J. Endocrinol. 71, 449–454.PubMedCrossRefGoogle Scholar
  47. 47.
    Wilson, J.T. (1970) Nature 225, 861–863.PubMedCrossRefGoogle Scholar
  48. 48.
    Shirasu, Y., Grantham, P.H., Yamamoto, R.S. and Weisburger, J.H. (1966) Cancer Res. 26, 600–606.PubMedGoogle Scholar
  49. 49.
    Shirasu, Y., Grantham, P.H., Weisburger, E.K. and Weisburger, J.H. (1967) Cancer Res. 27, 81–87.PubMedGoogle Scholar
  50. 50.
    Kramer, R.E., Greiner, J.W. and Colby, H.D. (1977) Biochem. Pharmacol. 26, 66–69.PubMedCrossRefGoogle Scholar
  51. 51.
    Gustafsson, J.-Å. and Skett, P. (1978) J. Endocrinol. 76 187–191.PubMedCrossRefGoogle Scholar
  52. 52.
    Skett, P., Eneroth, P. and Gustafsson, J.-Å. (1978) Mol. Cell. Endocrinol. 10, 21–27.PubMedCrossRefGoogle Scholar
  53. 53.
    Gustafsson, J.-Å., Ingelman-Sundberg, M., Stenberg, A. and Hökfelt, T. (1976) Endocrinology 98, 922–926.PubMedCrossRefGoogle Scholar
  54. 54.
    Kamberi, I.A., Mical, R.S. and Porter, J.C. (1971) Endocrinology 88, 1003–1011.PubMedCrossRefGoogle Scholar
  55. 55.
    Greenough, W.T., Carter, C.S., Steerman, C. and de Voogd, F.J. (1977) Brain Res. 126, 63–72.PubMedCrossRefGoogle Scholar
  56. 56.
    Pfaff, D.W. (1966) J. Endocrinol. 36, 415–416.PubMedCrossRefGoogle Scholar
  57. 57.
    D’orner, G. and Staudt, J. (1968) Neuroendocrinology 3, 136–140.CrossRefGoogle Scholar
  58. 58.
    Dörner, G. and Staudt, J. (1969) Neuroendocrinology 4, 278–281.PubMedCrossRefGoogle Scholar
  59. 59.
    Raisman, G. and Field, P.M. (1973) Brain Res. 54, 1–29.PubMedCrossRefGoogle Scholar
  60. 60.
    Libertun, C., Timiras, P.S. and Kragt, C.L. (1773) Neuroendocrinology 12, 73–85.CrossRefGoogle Scholar
  61. 61.
    Naftolin, F., “Ryan, K.J. and Petro, Z. (1971) J. Clin. Endocrinol. Metab. 33, 368–370.Google Scholar
  62. 62.
    Plapinger, L. and McEwen, B.S. (1973) Endocrinology 93, 1119–1128.PubMedCrossRefGoogle Scholar
  63. 63.
    Geliert, R.J., Bakke, J.L. and Lawrence, N. (1971) Fert. Steril. 22, 244–249.Google Scholar
  64. 64.
    Geliert, R.J., Heinrichs, W.L. and Swerdloff, R. (1974) Neuroendocrinology 16, 84–94.CrossRefGoogle Scholar
  65. 65.
    McEwen, B.S., Gerloch, J.L., Luine, V.N. and Lieberburg, I. (1977) Psychoneuroendocrinology 2, 249–255.PubMedCrossRefGoogle Scholar
  66. 66.
    Spona, J., Bieglmayer, C., Adamiker, D. and Gettmor, W. (1977) FEBS Lett. 76, 306–310.PubMedCrossRefGoogle Scholar
  67. 67.
    Luttge, W.G. and Whalen, R.E. (1970) Horm. Behav. 1, 265–281.CrossRefGoogle Scholar
  68. 68.
    McDonald, P.G. and Doughty, C. (1974) J. Endocrinol. 61, 95–103.PubMedCrossRefGoogle Scholar
  69. 69.
    Whalen, R.E. and Rezek, D.L. (1974) Horm. Behav. 5, 125–128.PubMedCrossRefGoogle Scholar
  70. 70.
    Gustafsson, J.-Å. and Stenberg, A. (1976) Science 191, 203–304.PubMedCrossRefGoogle Scholar
  71. 71.
    Gustafsson, J.-Å., Eneroth, P., Hökfelt, T. and Skett, P. (1978) Endocrinology in press.Google Scholar
  72. 72.
    Krulich, L., Hefco, E. and Aschenbrenner, J.E. (1975) Endocrinology 96, 107–118.PubMedCrossRefGoogle Scholar
  73. 73.
    Naess, O., Attramdal, A. and Aakvaag, A. (1975) Endocrinology 96, 1–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Mess, O. (1976) Steroids 27, 167–185.CrossRefGoogle Scholar
  75. 75.
    Gustafsson, J.Å., Pousette, A. and Svensson, E. (1976) J. Biol. Chem. 251, 4047–4054.PubMedGoogle Scholar
  76. 76.
    Pfaff, D. In “Primer of Neuroendocrine Function and Behaviour” Ed. Adler, N. (1978) in press.Google Scholar
  77. 77.
    Kubo, K., Gorski, R.A. and Kawakami, M. (1975) Neuroendocrinology 18, 176–181.PubMedCrossRefGoogle Scholar
  78. 78.
    Wrange, O., Nordenskjöld, B., Gustafsson, J.-Å. (1978) Anal. Biochem. 85, 461–475.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • Jan-Åke Gustafsson
    • 1
  • Peter Eneroth
    • 2
  • Barbro Haglund
    • 1
  • Tomas Hökfelt
    • 3
  • Agneta Mode
    • 1
  • Paul Skett
    • 1
  • Örjan Wrange
    • 1
  1. 1.Department of ChemistryKarolinska HospitalStockholm 60Sweden
  2. 2.Department of Histology, Karolinska InstitutetKarolinska HospitalStockholm 60Sweden
  3. 3.Hormonlaboratoriet, Department of Obstetrics and GynecologyKarolinska HospitalStockholm 60Sweden

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