5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isoenzymes of 5α-reductase, which vary in different tissues with age.

5α-Reductases catalyze the following chemical reaction:

Thus, the two substrates of these enzymes are a 3-oxo-5α-steroid and acceptor, whereas its two products are 3-oxo-Δ4-steroid and a reduced acceptor.

The enzyme is produced in many tissues in both males and females, in the reproductive tract, testes and ovaries,skin, seminal vesicles, prostate, epididymis and many organs, including the Nervous System. There are three isoenzymes of 5α-reductase: steroid 5α-reductase 1, 2, and 3 (SRD5A1, SRD5A2 and SRD5A3).

5α-Reductases act on 3-oxo (3-keto), Δ^4,5 C19/C21 steroids as its substrates. “3-keto” refers to the double bond of the third carbon to oxygen. Carbons 4 and 5 also have a double bond, represented by 'Δ^4,5'. The reaction involves a stereospecific and permanent break of the Δ^4,5 with the help of NADPH as a cofactor. A hydride anion (H−) is also placed on the α face at the fifth carbon, and a proton on the β face at carbon 4.

5α-R1 is expressed in fetal scalp and nongenital skin of the back, anywhere from 5 to 50 times less than in the adult. 5α-R2 is expressed in fetal prostates similar to adults. 5α-R1 is expressed mainly in the epithelium and 5α-R2 the stroma of the fetal prostate. Scientists looked for 5α-R2 expression in fetal liver, adrenal, testis, ovary, brain, scalp, chest, and genital skin, using immunoblotting, and were only able to find it in genital skin.

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