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steroid-5-alpha-reductase, alpha polypeptide 1
Identifiers
Symbol SRD5A1
Entrez 6715
HUGO 11284
OMIM 184753
RefSeq NM_001047
UniProt P18405
Other data
EC number 1.3.99.5
Locus Chr. 5 p15
steroid-5-alpha-reductase, alpha polypeptide 2
Identifiers
Symbol SRD5A2
Entrez 6716
HUGO 11285
OMIM 607306
RefSeq NM_000348
UniProt P31213
Other data
EC number 1.3.99.5
Locus Chr. 2 p23

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

Contents

Function

Steroidogenesis, showing both actions of 5-alpha reductase at bottom center.

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.)

Another function of the enzyme is participation in the creation of such neurosteroids as allopregnanolone and THDOC.

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, perhaps, increased levels of estradiol. Gynecomastia is a possible side-effect of 5-alpha reductase inhibition.

Pharmacology

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 allopregnanolone (5AR type I) and convert T to DHT(5AR type II)(1). Finasteride inhibits the function of only one of the isoenzymes (type 2), whereas 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. doi:10.1095/biolreprod.102.009142. PMID 12606426. http://www.biolreprod.org/cgi/pmidlookup?view=long&pmid=12606426.  
  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. doi:10.1530/eje.1.01927. PMID 15941927. http://eje-online.org/cgi/pmidlookup?view=long&pmid=15941927.  
  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. doi:10.1007/s11064-008-9718-5. PMID 18473173. http://dx.doi.org/10.1007/s11064-008-9718-5.  
  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

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