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5-alpha reductase

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steroid-5-alpha-reductase, alpha polypeptide 1
Symbol(s): SRD5A1
Locus: 5 p15
EC number 1.3.99.5
EntrezGene 6715
OMIM 184753
RefSeq NM_001047
UniProt P18405
steroid-5-alpha-reductase, alpha polypeptide 2
Symbol(s): SRD5A2
Locus: 2 p23
EC number 1.3.99.5
EntrezGene 6716
OMIM 607306
RefSeq NM_000348
UniProt P31213

5-alpha reductase is an enzyme involved in steroid metabolism.

Function

It converts testosterone, the male sex hormone, into the more potent dihydrotestosterone:

Note the major difference — the Δ4,5 double-bond on the A (leftmost) ring. (The other differences between the diagrams are unrelated to chemical structure.)

Isoenzymes

There are two isoenzymes, steroid 5-alpha reductase 1 and 2 (SRD5A1 and SRD5A2).[1][2]

The second isoenzyme is deficient in 5-alpha-reductase deficiency which leads to a form of intersexualism.

Production and inhibition

The enzyme is produced only in specific tissues of the male human body,[3] namely the skin, seminal vesicles, prostate and epididymis.

Inhibition of 5-alpha reductase results in decreased production of DHT, increased levels of testosterone and possibly increased levels of estradiol. Gynecomastia is a possible side effect of 5-alpha reductase inhibition.

Pharmacology

Main article: 5-alpha-reductase inhibitor

5-alpha-reductase inhibitor drugs are used in benign prostatic hyperplasia, prostate cancer and baldness. both isoforms are also produced in the brain, where they serve to create the neurosteroid Allopregnenolone (5AR type I) and convert T to DHT(5AR type II)(1). Finasteride inhibits the function of only one of the isoenzymes (type 2), while dutasteride inhibits both forms.

Research has indicated certain mushrooms have anti-5-alpha reductase activity.[4]

References

  1. Killian J, Pratis K, Clifton RJ, Stanton PG, Robertson DM, O'Donnell L (May 2003). 5alpha-reductase isoenzymes 1 and 2 in the rat testis during postnatal development. Biol. Reprod. 68 (5): 1711–8.
  2. Thiele S, Hoppe U, Holterhus PM, Hiort O (June 2005). Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males. Eur. J. Endocrinol. 152 (6): 875–80.
  3. Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E (October 2008). Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice. Neurochem. Res. 33 (10): 1990–2007.
  4. Chen, S., Y.C. Kao (1997), "Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase.", The Journal of Steroid Biochemistry and Molecular Biology (City of Hope, Duarte, California) 61: 107-115 

See also

External

Template:CH-CH oxidoreductases Template:Cholesterol and steroid metabolism enzymesTemplate:1.3-enzyme-stub


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