The 5α-reduction of 4-[1,2-3H]androstene-3,17-dione has been studied in liver nuclear preparations from male and female rats. Female rats were shown to possess a much higher enzyme activity (114.0 pmol of substrate converted/106 nuclei·min) than male rats (3.8 pmol of substrate converted/106 nuclei·min) and nuclei from female rats were used to study some properties of the enzyme. Liver nuclear 5α-reductase was shown to have a pH optimum about 6.5, to have an absolute requirement for NADPH as source of hydrogen and to be relatively unstable at +4°. The Km values determined for a series of substrates (4-[1,2-3H]androstene-3,17-dione, 17β-hydroxy-4-[1β,2β-3H]androsten-3-one(= [1β,-2β-3H]testosterone), 4-[7α-3H]pregnene-3,20-dione (= [7α-3H]progesterone), and 21-hydroxy-4-[1,2-3H]pregnene-3,20-dione (= [1,2-3H]deoxycorticosterone)) were in the range of 4.4-26.7 × 10-6 M whereas 11β,21-dihydroxy-4-[4-14C]-pregnene-3,20-dione (= [4-14C]corticosterone) and 4-[4-14C]-cholesten-3-one could not act as substrates for the enzyme during the experimental conditions used. The ability of some of these steroids to serve as substrates was parallelled by their ability to inhibit the 5α-reduction of 4-[1,2-3H]androstene-3,17-dione. The liver nuclear 5α-reductase thus resembled the previously described nuclear 5α-reductase in prostate and kidney and seemed to be different from liver microsomal 5α-reductase.
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