In vitro study of rat prostate 5 alpha-reductase activity and its inhibition.
A simple and rapid method of measuring 5 alpha-reductase (5 alpha-R) activity and of determining the kinetic parameters (KM and Vmax) of the enzyme is described. The 5 alpha-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 5 alpha-R activity were studied. Of the natural steroids, 17-OH-progesterone was found to have the highest inhibitory effect (IC50 = 1.35 microM), followed in decreasing order by progesterone (IC50 = 5.0 microM) and 4-androstene-3,17-dione (IC50 = 21.6 microM). Oestradiol-17 beta had practically no inhibitory effect. Of the synthetic steroids, 4-MA had the highest inhibitory effect (IC50 = 0.068 microM), followed by nortestosterone (IC50 = 7.4 microM) and RU-486 (Mifepristone) (IC50 = 115 microM). Even at 1000 microM, cyproterone acetate exerted no inhibitory effect. Of the nonsteroidal compounds, ketoconazole proved a weak inhibitor (IC50 = 115 microM), while flutamide was practically ineffective.
Faredin
I
I
First Department of Medicine, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Tóth
I
I
Oszlánczy
J
J
Scultéty
S
S
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D006728:Hormones / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D006728:Hormones; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase