Influence of Phenobarbital Pretreatment on the in Vitro Ring A Reduction of Δ4-3-Oxo-Steroids in Rat Liver Microsomes

  • Christer von Bahr
  • Belisario P. Lisboa
  • Sten Orrenius


The metabolism of 4-androstene-3, 17-dione has been studied in rat liver microsomes. Treatment of the animals with repeated doses of phenobarbital in vivo caused an enhanced rate of formation of 5α-androstane-3, 17-dione and of polar metabolites from this steroid. On the other hand, no significant increase was found in the 5β-reductase activity present in the soluble cytoplasm after phenobarbital administration to the rats. Carbon monoxide and oxidized cytochrome c abolished the formation of polar metabolites from 4-androstene-3, 17-dione but did not inhibit the 5α-reductase activity. The present findings indicate that the hydroxy-lation and 5α-reduction reactions, although both stimulated by phenobarbital treatment of the animals, do not involve common enzyme components.


Liver Induction 5α-reductase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Biggs, J.T., J.E. Carter, and K.C. Troop: Effect of heparin on the metabolism of cortisone by subcellular fractions of rat liver. Europ. J. Pharm. 2, 42–47 (1967).CrossRefGoogle Scholar
  2. 2.
    Conney, A. H, and A. Klutch: Increased activity of androgen hydroxylases in liver microsomes of rats pretreated with phenobarbital and other drugs. J. biol. Chem. 238, 1611–1617 (1963).PubMedGoogle Scholar
  3. 3.
    — W. Levin, M. Ikeda, R. Kuntzman, D.Y. Cooper, and O. Rosenthal: Inhibitory effect of carbon monoxide on the hydroxylation of testosterone by rat liver microsomes. J. biol. Chem. 243, 3912–3915 (1968).PubMedGoogle Scholar
  4. 4.
    — K. Schneidman, M. Jacobson, and R. Kuntzman: Drug-Induced Changes in steroid metabolism. Ann. N.Y. Acad. Sci. 123, 98–109 (1965).PubMedCrossRefGoogle Scholar
  5. 5.
    Deckx, R., J. Raus, C. Denef, and P. De Moor: Sex difference in the metabolism of Cortisol by rat liver. Steroids 6, 129–141 (1965).PubMedCrossRefGoogle Scholar
  6. 6.
    Ernster, L., P. Siekevitz, and G.E. Palade: Enzyme-structure relationships in the endoplasmic reticulum of rat liver. A Morphological and Biochemical study. J. Cell Biol. 15, 541–562 (1962).Google Scholar
  7. 7.
    Gustafsson, J.-Å., B.P. Lisboa, and J. Sjövall: Studies on the metabolism of C19-steroids in rat liver. 2. Biosynthesis of hydroxylated derivates of 17β-hydroxy-5α-Androstan-3-one in rat liver microsomes. Europ. J. Biochem. 5, 437–443 (1968).Google Scholar
  8. 8.
    — Studies on the metabolism of C19-steroids in rat liver. 3. Isolation and biosynthesis of 5α-androstanetriols in rat liver microsomes. Europ. J. Biochem. 6, 317–324 (1968).PubMedCrossRefGoogle Scholar
  9. 9.
    Kersten, H., u. Hj. Staudinger: Der Einfluß von Butazolidin auf die Cortisoninaktivierung in Leberhomogenanten. Klin. Wschr. 34, 523–525 (19PubMedCrossRefGoogle Scholar
  10. 10.
    Korus, W., H. Schriefers u. W. Dirscherl: Über den Stoffwechsel des Cortisons in der Rattenleber unter dem Einfluß von 3, 5-Dioxo-l, 2-diphenyl-4-n-butyl-pyrazolidin (Butazolidin). Arzneimittel-Forsch. 6, 596–598 (1956).Google Scholar
  11. 11.
    Krzanowski, P.T., and R.C. Troop: Inhibition of steroid Δ4 reductase by Heparin: Studies with desoxycorticosterone, progesterone, androstenedione and testosterone. Experientia (Basel) 24, 225–226 (1968).CrossRefGoogle Scholar
  12. 12.
    Kumagai, A., M. Otomo, S. Yano, N. Takeuchi, K. Nishino, H. Veda, S. Ko, and M. Kutamura: Inhibitors of the corticoid metabolism in vitro. Endocr. jap. 5, 122–126 (1958).PubMedCrossRefGoogle Scholar
  13. 13.
    Kuntzmann, R., M. Jacobson, K. Schneidman, and A.H. Conney: Similarities between oxidative drug-metabolizing enzymes and steroid hydroxylases in liver microsomes. J. Pharmacol. exp. Ther. 146, 280–285 (1964).Google Scholar
  14. 14.
    Leybold, K., u. Hj. Staudinger: Kinetische Untersuchungen über den Steroidstoffwechsel mit Lebermikrosomen weiblicher Ratten. Biochem. Z. 331, 399–409 (1959).Google Scholar
  15. 15.
    — Wirkung von Pharmaka auf den Steroidstoffwechsel von Rattenlebermikrosomen. Klin. Wschr. 39, 952–953 (1961).PubMedCrossRefGoogle Scholar
  16. 16.
    Lisboa, B.P.: Chromatographic analysis of lipids, p. 57. Vol. II, G.V. Mabinetti, ed. New York: Dekker 1968.Google Scholar
  17. 17.
    — In: Steroids and terpenoids, R.B. Clayton, ed. (Methods in enzymology, S.P. Colowick, and M.O. Kaplan, eds.-in-chief). New York: Acad. Press. Inc. (in press.).Google Scholar
  18. 18.
    — J.-Å. Gustafsson, and J. Sjövall: Studies on the Metabolism of C19-steroids in rat liver. 1. Hydroxylation of testosterone in rat liver microsomes. Europ. J. Biochem. 4, 496–505 (1968).PubMedCrossRefGoogle Scholar
  19. 19.
    Löw, H., and I. Vallin: Succinate-linked diphosphopyridine nucleotide reduction in submitochondrial particles. Biochim. biophys. Acta (Amst.) 69, 361–374(1963).CrossRefGoogle Scholar
  20. 20.
    Lowey, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall: Protein measurement with the folin phenol reagent. J. biol. Chem. 193, 265–275 (1951).Google Scholar
  21. 21.
    McGuire, J.S., de., V.W. Hollis, and G.M. Tomkins: Some characteristics of the microsomal Steroid reductases (5a) of rat liver. J. biol. Chem. 235, 3112–3117 (1960).Google Scholar
  22. 22.
    Ofner, P.: A preliminary investigation of the products of the metabolism of testosterone by rat liver in vitro. Biochem. J. 61, 287–297 (1955).PubMedGoogle Scholar
  23. 23.
    Orrenius, S., and B.P. Lisboa: In: Hydroxylation of drugs and chemical action of their products within the organism, J. Wagner, ed. London: Acad. Press. Inc. (in press).Google Scholar
  24. 24.
    Scheiefers, H., W. Cremer, u. M. Otto: Sexualcharakteristika des Stoffwechsels von Testosteron in der perfundierten Rattenleber. Hoppe-Seylers Z. physiol. Chem. 348, 183–193 (1967).CrossRefGoogle Scholar
  25. 25.
    Sholiton, L.J., E.E. Werk, and J. MacGee: The in vitro effect of 5, 5′-Di-phenylhydantoin on the catabolism of cortisol by rat liver. Metabolism 13, 1382–1392 (1964).PubMedCrossRefGoogle Scholar
  26. 26.
    Tephly, T.R., and G.J. Mannering: Inhibition of drug metabolism. V. Inhibition of drug metabolism by steroids. Mol. Pharm. 4, 10–14 (1968).Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1969

Authors and Affiliations

  • Christer von Bahr
    • 1
    • 2
  • Belisario P. Lisboa
    • 1
    • 3
  • Sten Orrenius
    • 1
    • 2
  1. 1.Department of BiochemistryUniversity of Stockholm and HormonlaboratorietStockholmSweden
  2. 2.Biokeminska InstitutionenKungl. Universitetet i StockholmStockholmSweden
  3. 3.HormonlaboratorietStockholm 60Sweden

Personalised recommendations