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.
KeywordsTestosterone International Urology Flutamide Mifepristone Cyproterone Acetate
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- 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
- 7.Julesz, M., Faredin, I., Tóth, I.: Steroids in Human Skin. Akadémiai Kiadó, Budapest 1971, p. 166.Google Scholar
- 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
- 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