International Urology and Nephrology

, Volume 24, Issue 2, pp 145–154 | Cite as

In vitro study of rat prostate 5α-reductase activity and its inhibition

  • I. Faredin
  • I. Tóth
  • J. Oszlánczy
  • S. Scultéty
Article

Abstract

A simple and rapid method of measuring 5α-reductase (5α-R) activity and of determining the kinetic parameters (KM and Vmax) of the enzyme is described. The 5α-R activity in the homogenate of the prostate of Wistar rats aged 8–12 weeks was established, and the effects of natural and synthetic steroids and of non-steroidal antiandrogens (IC50) upon the 5α-R activity were studied. Of the natural steroids, 17-0H-progesterone was found to have the highest inhibitory effect (IC50=1.35 μM), followed in decreasing order by progesterone (IC50=5.0 μM) and 4-androstene-3,17-dione (IC50=21.6 μM). Oestradiol-17β had practically no inhibitory effect. Of the synthetic steroids, 4-MA had the highest inhibitory effect (IC50=0.068 μM), followed by nortestosterone (IC50=7.4 μM) and RU-486 (Mifepristone) (IC50=115 μM). Even at 1000 μM, cyproterone acetate exerted no inhibitory effect. Of the nonsteroidal compounds, ketoconazole proved a weak inhibitor (IC50=115 μM), while flutamide was practically ineffective.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bingham, K. D., Shaw, D. A.: The metabolism of testosterone by human male scalp skin.J. Endocrinol., 57, 111 (1973).PubMedCrossRefGoogle Scholar
  2. 2.
    Blohm, T. R., Laughlin, M. E., Benson, H. D., Johnston, J. O., Wright, C. L., Schatzman, G. L., Weintraub, C. M.: Pharmacological induction of 5α-reductase deficiency in the rat: Separation of testosterone-mediated and 5α-dihydrotestosterone-mediated effects.Endocrinology 119, 959 (1986).PubMedGoogle Scholar
  3. 3.
    Bruchovsky, N., Wilson, J. D.: The conversion of testosterone to 5α-androstan-17β-ol-3-one by rat prostate in vivo and in vitro.J. Biol. Chem., 243, 2012 (1968).PubMedGoogle Scholar
  4. 4.
    Bruchovsky, N., Wilson, J. D.: The intranuclear binding of testosterone and 5α-androstan-17β-ol-3-one by rat prostate.J. Biol. Chem., 243, 5953 (1968).PubMedGoogle Scholar
  5. 5.
    George, F. W., Peterson, K. G.: 5α-Dihydrotestosterone formation is necessary for embryogenesis of the rat prostate.Endocrinology 122, 1159 (1988).PubMedGoogle Scholar
  6. 6.
    Imperato-McGinley, J., Binienda, Z., Arthur, A., Minenberg, D. T., Vaugham, E. D., Quimley, F. W.: The development of the male pseudohermaphrodite rat using an inhibitor of the enzyme 5α-reductase.Endocrinology, 116, 807 (1985).PubMedGoogle Scholar
  7. 7.
    Julesz, M., Faredin, I., Tóth, I.: Steroids in Human Skin. Akadémiai Kiadó, Budapest 1971, p. 166.Google Scholar
  8. 8.
    Kadohama, N., Wakisaka, M., Kinn, U., Karr, J. P., Murphy, G. P., Sandberg, A. A.: Retardation of prostate tumor progression in the Noble rat by 4-methyl-4-aza-steroidal inhibitors of 5α-reductase.J. Natl. Cancer Inst., 71, 475 (1985).Google Scholar
  9. 9.
    Liang, T., Cascieri, M. A., Cheung, A. H., Reynolds, G. F., Rasmusson, G. H.: Species differences in prostatic steroid 5α-reductases of rat, dog and human.Endocrinology, 117, 571 (1985).PubMedGoogle Scholar
  10. 10.
    Lowry, O. H., Rosenbrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin Phenol reagent.J. Biol. Chem., 193, 265 (1951).PubMedGoogle Scholar
  11. 11.
    Metcalf, B. W., Levy, M. A., Holt, D. A.: Inhibitors of steroid 5α-reductase in benign prostatic hyperplasia, male pattern baldness and acne. TiPS10, 491 (1989).PubMedGoogle Scholar
  12. 12.
    Metcalf, B. W., Holt, D. A., Levy, M. A., Erb, J. M., Heaslip, J. J., Barndt, M., Oh, H.-J.: Potent inhibition of human steroid 5α-reductase (EC 1.3.1.30.) by 3-androstene-3-carboxylic acids.Bioorg. Chem. 17, 372 (1989).CrossRefGoogle Scholar
  13. 13.
    Sansone, G., Reisner, R. M.: Differential rates of conversion of testosterone to dihydrotestosterone in acne and normal human skin—a possible pathogenic factor in acne.J. Invest. Dermatol., 56, 366 (1971).PubMedCrossRefGoogle Scholar
  14. 14.
    Schultz, F. M., Wilson, J. D.: Virilization of the Wolffian duct in the rat fetus by various androgens.Endocrinology, 94, 979 (1974).PubMedCrossRefGoogle Scholar
  15. 15.
    Shimazaki, J., Kurihara, H., Ito, G., Shida, K.: Testosterone metabolism in prostate; formation of androstan-17β-ol-3-one and androst-4-ene-3,17-dione, and inhibitory effect of natural and synthetic estrogens.Gumma J. Med. Sci., 14, 313 (1965).Google Scholar
  16. 16.
    Waller, D. P., Martin, A., Vickery, B. H., Zaneveld, L. J. D.: The effect of ketoconazole on fertility of male rats.Contraception, 41, 411 (1990).PubMedCrossRefGoogle Scholar
  17. 17.
    Wenderoth, U. K., George, F. W., Wilson, J. D.: The effect of a 5α-reductase inhibitor on androgen-mediated growth of the dog prostate.Endocrinology, 113, 569 (1983).PubMedGoogle Scholar
  18. 18.
    Wilson, J. D.: The pathogenesis of benign prostatic hyperplasia.Am. J. Med., 68, 745 (1980).PubMedCrossRefGoogle Scholar
  19. 19.
    Wilson, J. D., Lasnitzki, J.: Dihydrotestosterone formation in fetal tissues of the rabbit and rat.Endocrinology, 89, 659 (1971).PubMedCrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó 1992

Authors and Affiliations

  • I. Faredin
    • 1
  • I. Tóth
    • 1
  • J. Oszlánczy
    • 2
  • S. Scultéty
    • 2
  1. 1.Endocrine Unit, First Department of MedicineSzent-Györgyi Albert Medical UniversitySzegedHungary
  2. 2.Department of UrologySzent-Györgyi Albert Medical UniversitySzegedHungary

Personalised recommendations