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


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.

This is a preview of subscription content, log in to check access.


  1. 1.

    Bingham, K. D., Shaw, D. A.: The metabolism of testosterone by human male scalp skin.J. Endocrinol., 57, 111 (1973).

    PubMed  CAS  Article  Google 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).

    PubMed  CAS  Google 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).

    PubMed  CAS  Google 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).

    PubMed  CAS  Google Scholar 

  5. 5.

    George, F. W., Peterson, K. G.: 5α-Dihydrotestosterone formation is necessary for embryogenesis of the rat prostate.Endocrinology 122, 1159 (1988).

    PubMed  CAS  Google 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).

    PubMed  CAS  Google 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).

    PubMed  CAS  Google 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).

    PubMed  CAS  Google 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).

    PubMed  CAS  Google 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 by 3-androstene-3-carboxylic acids.Bioorg. Chem. 17, 372 (1989).

    Article  CAS  Google 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).

    PubMed  Article  CAS  Google 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).

    PubMed  CAS  Article  Google 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).

    CAS  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).

    PubMed  Article  CAS  Google 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).

    PubMed  CAS  Google Scholar 

  18. 18.

    Wilson, J. D.: The pathogenesis of benign prostatic hyperplasia.Am. J. Med., 68, 745 (1980).

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Wilson, J. D., Lasnitzki, J.: Dihydrotestosterone formation in fetal tissues of the rabbit and rat.Endocrinology, 89, 659 (1971).

    PubMed  CAS  Article  Google Scholar 

Download references

Author information



Additional information

Preliminary results were presented at the 12th Congress of the Hungarian Society of Endocrinology and Metabolism, Budapest, April 1988.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Faredin, I., Tóth, I., Oszlánczy, J. et al. In vitro study of rat prostate 5α-reductase activity and its inhibition. International Urology and Nephrology 24, 145–154 (1992).

Download citation


  • Testosterone
  • International Urology
  • Flutamide
  • Mifepristone
  • Cyproterone Acetate