Steroid 5-alpha-reductase (5AR) (5AR)

Steroid 5-alpha-reductase (5AR) is a membrane-bound enzyme that plays a critical role in the metabolism of steroid hormones by catalyzing the NADPH-dependent reduction of the C4-C5 double bond in various 3-oxo-delta-4 steroids [UniProt]. Its most significant physiological function is the conversion of testosterone into dihydrotestosterone (DHT), a more potent androgen that is essential for the development of male reproductive organs and secondary sexual characteristics [StatPearls]. There are three known isoforms of the enzyme—SRD5A1, SRD5A2, and SRD5A3—which exhibit distinct tissue distributions and pH optima; for instance, Type 2 is primarily expressed in the prostate and hair follicles, while Type 1 is found in the skin and liver [UniProt, Wikipedia]. Overactivity of 5AR or elevated DHT levels are strongly associated with clinical conditions such as benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern baldness) [StatPearls, Wikipedia]. Pharmacological inhibitors, such as finasteride and dutasteride, are used to treat these conditions by reducing systemic and local DHT concentrations [PubChem]. Beyond androgen metabolism, 5AR is also involved in the synthesis of neurosteroids like allopregnanolone, which influences GABAergic signaling in the brain, potentially explaining some of the neuropsychiatric side effects associated with its inhibition [StatPearls].

Other names

3-oxo-5-alpha-steroid 4-dehydrogenaseSRD5A5-alpha-reductase5-AR

Competitive inhibition of the steroid 5-alpha-reductase enzyme isoforms, which prevents the conversion of testosterone to the more potent androgen dihydrotestosterone (DHT), thereby reducing androgenic stimulation in target tissues like the prostate and scalp [StatPearls, PubChem].