5α-Reductase type 3 (SRD5A3)

5α-Reductase type 3 (SRD5A3) is a membrane-bound NADPH-dependent enzyme in the steroid 5α-reductase family. It catalyzes the reduction of Δ⁴,3-keto steroids, notably converting testosterone to dihydrotestosterone (DHT), and also reduces androstenedione and progesterone to their respective 5α-dihydro forms[3][4]. In addition to its role in androgen metabolism, it is also essential for N-linked protein glycosylation due to its involvement in dolichol biosynthesis. SRD5A3 is widely expressed in multiple tissues, including prostate, liver, muscle, skin, kidney, brain regions (such as hippocampus and cerebellum), and is upregulated in various cancers, especially prostate cancer and castration-resistant forms[4][5][6]. Its enzymatic activity is less sensitive to dutasteride inhibition compared to types 1 and 2, suggesting unique therapeutic challenges and the need for specific targeting in certain disease contexts[4]. It has attracted attention as a biomarker and potential drug target in oncology, particularly in advanced and hormone-independent prostate cancers[4][6].

Other names

Steroid 5α-reductase 35-alpha reductase type 3SRD5A3steroid 5-alpha-reductase 3Steroid 5AR3

Inhibition of SRD5A3 decreases conversion of Δ⁴-3-keto steroids (e.g., testosterone, androstenedione, progesterone) to their 5α-reduced metabolites (e.g., DHT) - Reduces androgen signaling, which can be therapeutic in androgen-dependent cancers