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

3-oxo-5-alpha-steroid 4-dehydrogenase, commonly known as 5-alpha-reductase (SRD5A), is a family of membrane-bound enzymes that catalyze the NADPH-dependent reduction of the Δ4,5 double bond in various steroids [1, 2]. The two primary isoforms, Type 1 (SRD5A1) and Type 2 (SRD5A2), play a central role in androgen physiology by converting testosterone into dihydrotestosterone (DHT), a significantly more potent androgen [2, 3]. Type 1 is predominantly expressed in the skin, liver, and brain, while Type 2 is the major isoform in the prostate and genitourinary tract [1, 6]. Excessive DHT activity is a key driver in the pathogenesis of benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern baldness) [3, 6]. Pharmacological inhibitors such as finasteride (Type 2 selective) and dutasteride (dual inhibitor) are widely used to treat these conditions by reducing systemic and local DHT levels [3, 5]. Beyond androgen metabolism, these enzymes are involved in bile acid biosynthesis and the production of neurosteroids like allopregnanolone, which may explain some of the non-sexual side effects associated with their inhibition [4, 7]. Safety concerns include sexual dysfunction, potential risks of high-grade prostate cancer, and teratogenicity, necessitating careful patient monitoring [3, 7].

Other names

5-alpha-reductaseSteroid 5-alpha-reductaseSRD5A1SRD5A23-oxo-5-alpha-steroid 4-dehydrogenase 13-oxo-5-alpha-steroid 4-dehydrogenase 2S5AR

Competitive inhibition of the 5-alpha-reductase enzyme isoforms, which prevents the conversion of testosterone to the more potent androgen dihydrotestosterone (DHT), thereby reducing androgenic signaling in target tissues [2, 3, 6].