Steroid 5α-reductase Types 1 and 2 (SRD5A1/SRD5A2)

Steroid 5α-reductases, specifically types 1 (SRD5A1) and 2 (SRD5A2), are integral membrane oxidoreductase enzymes crucial for steroid metabolism. Both catalyze the NADPH-dependent irreversible reduction of testosterone to the more potent dihydrotestosterone (DHT), and also act on other steroids like progesterone. SRD5A1 is encoded by the SRD5A1 gene and is expressed in tissues such as skin, liver, and prostate. SRD5A2, encoded by the SRD5A2 gene, is predominantly expressed in the prostate, skin, and reproductive tissues, playing a critical role in male fetal genitalia differentiation, prostate development, and hair follicle physiology. Aberrant regulation, overactivity, or genetic mutations in these enzymes are implicated in various hormone-related disorders, including benign prostatic hyperplasia (BPH), prostate cancer, androgenic alopecia, 5α-reductase deficiency, and disorders of sexual development. As validated therapeutic targets, they are inhibited by competitive inhibitors such as finasteride (selective for type 2) and dutasteride (inhibiting both types 1 and 2) for the treatment of these androgen-driven conditions.

Other names

3-oxo-5α-steroid 4-dehydrogenase 15α-reductase type 1Steroid 5-alpha-reductase 13-oxo-5α-steroid 4-dehydrogenase 25α-reductase type 2Steroid 5-alpha-reductase 25α-reductases (5ARs)

Competitive inhibition of testosterone reduction to dihydrotestosterone (DHT); NADPH-dependent reduction of C=C double bond in steroids. Finasteride selectively inhibits type 2, while Dutasteride inhibits both types 1 and 2.