SRD5A1 gene

The SRD5A1 gene (SRD5A1 stands for: steroid 5 alpha-reductase 1) is a protein-coding gene located on chromosome 5p15.31. Gene Ontology (GO) annotations for this gene include electron transfer activity and 3-oxo-5-alpha-steroid 4 dehydrogenase activity. An important paralog of this gene is SRD5A2.

The SRD5A1 gene encodes the steroid 5-alpha reductase (EC 1.3.99.5). The term steroid 5-alpha reductase, SRD5 for short, generally refers to 3 isoenzymes (types I-III) that catalyze the conversion of testosterone into its more effective form dihydrotestosterone, among other things.

• Type I of steroid 5α-reductase: This type is encoded by the SRD5A1 gene and is mainly found in the brain, epididymis and skin. Type I plays an important role in the biosynthesis of allopregnanolone (ALLO), where this steroid reductase converts progesterone into 5α-dihydroprogesterone, from which allopregnanolone is produced in a further step.
• Type II of steroid 5α-reductase: This type is encoded by the SRD5A2 gene and is mainly found in the muscles, liver, kidneys and prostate. In benign prostatic hyperplasia (BPH), type II of steroid 5α-reductase is significantly increased.
• Type III of steroid 5α-reductase: This isoform is encoded by the SRD5A3 gene. It is mainly found in the female and male reproductive organs as well as in the brain, skin, pancreas, spleen, kidneys, heart, stomach and liver. Type III converts polyprenol to dolichol.

Mutations in the SRD5A2 gene result in a steroid 5α-reductase deficiency. In men, it leads to intersexuality and hypospadias, among other things.

In women, increased 5α-reductase activity is associated with a greater risk of polycystic ovary syndrome(PCOS).

Inhibition of steroid 5α-reductase is used to treat benign prostatic hyperplasia and androgenetic alopecia (steroid 5α-reductase inhibitors, see finasteride below).

Mutations in the SRD5A3 gene lead to a disruption in the biosynthesis of dolichol, which in turn impairs the N-glycosylation of proteins. Those affected suffer from congenital glycosylation disorder type Iq (CDG Iq).