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Rat liver 3 alpha-hydroxysteroid dehydrogenase.

T M Penning, T E Smithgall, L J Askonas

    Steroids
    |April 1, 1986
    PubMed
    Summary
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    3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) is a multifunctional enzyme involved in androgen metabolism, prostaglandin redox, and carcinogen detoxification. Further research is needed to understand its in vivo roles and potential drug interactions.

    Area of Science:

    • Biochemistry
    • Enzymology
    • Carcinogenesis

    Background:

    • 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) traditionally catalyzes androgen metabolism.
    • Novel functions include prostaglandin oxidoreduction and detoxification of trans-dihydrodiols, which are proximate carcinogens.

    Purpose of the Study:

    • To investigate the multifunctional roles of 3 alpha-HSD beyond androgen metabolism.
    • To explore the implications of 3 alpha-HSD's novel functions in prostaglandin metabolism, carcinogen detoxification, and drug interactions.

    Main Methods:

    • Quantification of novel reactions using homogeneous 3 alpha-HSD enzyme preparations.
    • Analysis of inhibition of purified 3 alpha-HSD by anti-inflammatory drugs.

    Main Results:

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    • 3 alpha-HSD demonstrates significant activity in prostaglandin oxidoreduction and trans-dihydrodiol detoxification.
    • Therapeutically relevant concentrations of anti-inflammatory drugs inhibit purified 3 alpha-HSD.

    Conclusions:

    • 3 alpha-HSD's multifunctional nature raises critical questions about its in vivo roles in hormone metabolism, inflammation, and cancer.
    • The enzyme's inhibition by anti-inflammatory drugs suggests potential pharmacological relevance and a possible role in modulating carcinogenesis.