3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1) (SRD5A1)

3-oxo-5-alpha-steroid 4-dehydrogenase 1, commonly known as 5-alpha reductase type 1 (SRD5A1), is a membrane-bound oxidoreductase enzyme that plays a central role in human steroid metabolism [1, 2]. It is responsible for the irreversible conversion of testosterone into 5-alpha-dihydrotestosterone (DHT), an androgen with significantly higher affinity for the androgen receptor, as well as the reduction of other steroids like progesterone and deoxycorticosterone [2, 12, 19]. Unlike the type 2 isoform which is localized mainly in the prostate, SRD5A1 is widely expressed in the skin (sebaceous glands), liver, and brain, making it a key regulator of peripheral androgen activity and neurosteroid production [7, 12]. In the brain, its activity leads to the synthesis of neuroactive steroids such as allopregnanolone, which modulate GABA-A receptors and influence mood and behavior [2, 22]. Pathological overexpression of this enzyme is associated with conditions like acne, hirsutism, and androgenetic alopecia, and it is a therapeutic target for dual 5-alpha reductase inhibitors like dutasteride [3, 9, 12]. Clinical inhibition of this target successfully treats benign prostatic hyperplasia and hair loss but carries risks of sexual dysfunction and neuropsychiatric side effects due to its broad physiological roles [4, 5, 24].

Other names

5-alpha reductase type 1Steroid 5-alpha-reductase 1SRD5A1S5AR1Steroid-5-alpha-reductase alpha polypeptide 1

Irreversible inhibition of the 5-alpha reductase enzyme, preventing the reduction of testosterone to dihydrotestosterone (DHT) [4, 12].