5reductase

5-Reductase, or steroid 5-alpha-reductase, refers to a group of enzymes that catalyze the reduction of the carbon-4,5 double bond in certain steroids, most notably converting testosterone into dihydrotestosterone (DHT). In humans, several isoenzymes have been identified, including SRD5A1, SRD5A2, and SRD5A3. These enzymes differ in tissue distribution and substrate preference, and they influence the local production of DHT, a potent androgen with high affinity for the androgen receptor.

SRD5A2 is the predominant form in the prostate and external genitalia, and it plays a key role in embryonic development of male external genitalia as well as in postnatal androgen action on the prostate, skin, and hair follicles. SRD5A1 is more widely expressed in skin and liver and contributes to local DHT production in non-prostatic tissues. SRD5A3 is involved in other metabolic pathways, including dolichol biosynthesis, and has a less direct role in androgen signaling.

Clinically, defects in SRD5A2 cause 5-alpha-reductase deficiency, a sex development disorder in 46,XY individuals characterized by undervirilized genitalia at birth and often virilization at puberty. Pharmacologic inhibitors of 5-alpha-reductase, such as finasteride (selective for SRD5A2) and dutasteride (inhibits both SRD5A1 and SRD5A2), are used to treat benign prostatic hyperplasia and androgenetic alopecia. Side effects can include decreased libido and sexual dysfunction, and these drugs can affect serum PSA levels.