Overexpression of aldo-keto reductase 1C3 (AKR1C3) in LNCaP cells diverts androgen metabolism towards testosterone resulting in resistance to the 5α-reductase inhibitor finasteride

    Michael C. Byrns, Rebekka Mindnich, Ling Duan, Trevor M. Penning
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    TLDR Too much AKR1C3 enzyme causes resistance to finasteride by increasing testosterone.
    The study found that overexpression of the enzyme AKR1C3 in LNCaP cells led to a diversion of androgen metabolism towards testosterone, resulting in resistance to the 5α-reductase inhibitor finasteride. This was due to AKR1C3 redirecting A4-Adione metabolism towards testosterone production, leading to increased levels of testosterone and decreased sensitivity to finasteride. The study suggests that inhibition of AKR1C3 could prevent the conversion of A4-Adione to testosterone and the conversion of 5a-androstane-3,17-dione to 5a-DHT, which are potent ligands for the AR, and could have therapeutic consequences for the use of inhibitors that target 5α-reductase in prostate cancer.
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