3-Oxo-5α-steroid 4-dehydrogenase 2 (Steroid 5α-reductase Type 2) (SRD5A2)

Steroid 5α-reductase type 2 (SRD5A2) is a microsomal enzyme that catalyzes the irreversible conversion of testosterone into the more potent androgen dihydrotestosterone (DHT)[1][4]. The enzyme is expressed at high levels in androgen-sensitive tissues, particularly the prostate, and plays a central role in sexual differentiation and androgen physiology[1][3]. Beyond its primary function, SRD5A2 also metabolizes other steroid hormones including progesterone and corticosterone into their corresponding 5-alpha-reduced metabolites[1][8]. SRD5A2 is a well-validated therapeutic target for conditions including benign prostatic hyperplasia and male pattern baldness, both mediated by excessive DHT signaling[1][4]. Finasteride and dutasteride—selective 4-azasteroid inhibitors—potently block SRD5A2 activity, reducing serum DHT levels by approximately 71% within 6 months of treatment[2]. Genetic deficiencies in SRD5A2 result in 5α-reductase 2 deficiency, a condition associated with atypical male genitalia development and various forms of intersex conditions, underscoring the enzyme's critical role in male sexual development[4]. Inhibition of this enzyme represents a major class of approved therapeutics targeting androgen metabolism.

Other names

3-oxo-5-alpha-steroid 4-dehydrogenase 25 alpha-SR2S5AR 2SR type 2Type II 5-alpha reductaseTestosterone 5α-reductase4-Ene-3-ketosteroid-5α-oxidoreductase

Irreversible competitive inhibition (finasteride and dutasteride are 4-azasteroid inhibitors). Reduction of testosterone conversion to DHT, leading to decreased DHT levels and increased circulating testosterone and estradiol.