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  • Title: Characterization of the purified pituitary cytosolic NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase.
    Author: Campbell JS, Karavolas HJ.
    Journal: J Steroid Biochem Mol Biol; 1990 Nov 30; 37(4):535-43. PubMed ID: 2278837.
    Abstract:
    The purified cytosolic 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) from female rat pituitary which catalyzes the reversible conversion of 5 alpha-dihydroprogesterone (5 alpha-DHP) to 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) has been characterized in terms of its steroid substrate specificity, dihydrodiol dehydrogenase activity and inhibition by drugs such as medroxyprogesterone and indomethacin. The purified enzyme has a strong preference for the C21 progestin steroid substrates, 5 alpha-DHP and 3 alpha, 5 alpha-THP, over the corresponding C19 androgenic steroid substrates, 5 alpha-dihydrotesterone (5 alpha-DHT) and 3 alpha, 5 alpha-tetrahydrotestosterone (3 alpha, 5 alpha-THT). The apparent Km for 5 alpha-DHP (80 nM) is about 250 times lower than the Km for the androgenic steroid, 5 alpha-DHT (21 microM). In the oxidative direction, the apparent Km for 3 alpha, 5 alpha-TP (1.4 microM) is about 3-fold lower than the Km for the androgenic steroid, 3 alpha, 5 alpha-THT (4.2 microM). A number of other naturally occurring 3-keto- and 3 alpha(beta)-hydroxy-steroids were assessed for their ability to act as inhibitors (alternate substrates) of the 3 alpha-reduction of 5 alpha-DHP catalyzed by the purified 3 alpha-HSOR. None of the 3 beta- or 5 beta-isomers had any effect. Of the other 3-keto and 3 alpha- steroids tested, only deoxycorticosterone and the ovarian progestins showed any significant inhibition. These may be acting as inhibitors since there was little, if any, direct 3 alpha-reduction of progesterone to 3 alpha-hydroxy-4-pregnen-20-one. Unlike the liver cytosolic 3 alpha-HSOR, the pituitary enzyme has no associated dihydrodiol (quinone) dehydrogenase activity. This enzyme is similar to other cytosolic 3 alpha-HSORs from liver and brain in that it is potentially inhibited by indomethacin and by medroxyprogesterone.
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