Steroid 5-alpha-reductase 1 (SRD5A1)

Steroid 5-alpha-reductase 1 (SRD5A1) is an NADPH-dependent enzyme localized to the endoplasmic reticulum membrane that catalyzes the irreversible reduction of the Δ4,5 double bond in 3-oxo-Δ4 steroids, such as testosterone and androstenedione, to produce potent 5α-reduced androgens and neurosteroids[1][2][3]. Type 1 and type 2 isoforms play distinct tissue-specific roles: SRD5A1 is expressed predominantly in the liver, skin, scalp, brain, and certain peripheral tissues, while its activity is important for androgen and neurosteroid metabolism, affecting processes like myelination, neurotransmission, and hormonal regulation[2][3]. Dysregulation of SRD5A1 has been implicated in prostate cancer progression (where its expression/activity can be altered), and it is targeted therapeutically by drugs such as dutasteride to modulate androgen levels[1][3]. Both type 1 and type 2 are targeted in hormonal disorders, but only dutasteride robustly inhibits SRD5A1, making it useful for broader suppression of androgen activation[1]. The structure of SRD5A1 features seven transmembrane domains and uses NADPH as a hydride donor for its catalytic activity[1][2].

Other names

5α-reductase type 15-alpha-reductase type 15α-R15-alpha-R1NADPH-dependent 3-oxo-Δ4-steroid 5β-reductase 1

Competitive enzyme inhibition (e.g., dutasteride binds to and inhibits the enzyme activity, preventing conversion of testosterone to dihydrotestosterone (DHT))