3-oxo-5α-steroid 4-dehydrogenase (5α-reductase) (SRD5A)

3-oxo-5α-steroid 4-dehydrogenase, widely known as 5-alpha reductase, is a family of membrane-bound enzymes responsible for the NADPH-dependent reduction of 3-oxo-Δ4 steroids [4, 16]. Its primary physiological function is the conversion of testosterone into dihydrotestosterone (DHT), the most potent endogenous androgen [2, 9]. The enzyme family consists of three isoforms—SRD5A1, SRD5A2, and SRD5A3—which are distributed across tissues such as the prostate, skin, liver, and brain [4, 12]. Beyond androgen metabolism, these enzymes are involved in the synthesis of neurosteroids like allopregnanolone and the metabolism of bile acids [10, 19]. Dysregulation of 5-alpha reductase activity is a key driver in the pathogenesis of benign prostatic hyperplasia (BPH) and androgenetic alopecia [13, 14]. Pharmacological inhibitors, such as finasteride and dutasteride, are clinically used to reduce DHT levels and manage these conditions [3, 9]. However, inhibition can lead to adverse effects, including sexual dysfunction and mood disorders, often attributed to the depletion of neuroactive steroids [10, 17]. Genetic mutations in the SRD5A2 gene result in 5-alpha-reductase deficiency, a condition characterized by ambiguous genitalia in males at birth [6, 19]. Monitoring of patients on 5-alpha reductase inhibitors often involves tracking prostate-specific antigen (PSA) levels, which are typically halved by the medication [13, 14]. Overall, this enzyme family represents a critical intersection of endocrine signaling, metabolic health, and dermatological conditions [19].

Other names

5-alpha reductaseSteroid 5-alpha-reductase3-oxosteroid delta-4-dehydrogenaseTestosterone 5-alpha-reductaseSRD5A

Irreversible or competitive inhibition of 5-alpha reductase enzymes, leading to decreased conversion of testosterone to dihydrotestosterone (DHT).