SRD5A2 binds SRD5A2 inhibitors

Stable Identifier
R-HSA-9705794
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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The conversion of testosterone (TEST) to the most potent androgen, 5-alpha-dihydrotestosterone (DHTEST), is catalyzed by microsomal 5alpha-steroid reductases 1-3 (SRD5A1-3). SRD5As are highly expressed in the prostate, the skin, and other androgen target sites. Benign prostatic hyperplasia (BPH) is a pathologic process that can lead to the development of lower urinary tract symptoms (LUTS) in men. BPH refers to stromal and glandular epithelial hyperplasia that occurs in the zone of the prostate that surrounds the urethra. This overgrowth is dependent mainly on androgens, particularly DHTEST. Since SRD5As are responsible for the production of DHTEST, SRD5A inhibitors can be used in the treatment of symptomatic BPH (Rasmusson et al. 1986, Gisleskog et al. 1998).

The azasteroids finasteride and dutasteride are approved for human use to treat BPH (Sandhu 2009). Dutasteride can block all three SRD5A isoforms and can decrease DHTEST levels in the blood by up to 98% (Keam & Scott 2008, Yamana et al. 2010). In contrast, finasteride (Hasinki et al. 1992) only inhibits type II and III isoenzymes so is able to achieve a reduction in circulating DHTEST of only 65 to 70% (Yamana et al. 2010, Aggarwal et al. 2010). However, these two drugs decrease DHTEST levels in the prostate gland to a similar level, where the SRD5A2 isoform predominates.

The dicarboxylic acid azelaic acid is a potent inhibitor of SRD5A in human skin and could be an effective agent in the treatment of androgen related pathology of human skin such as various types of acne and cutaneous hyperpigmentary disorders (Stamatiadis et al. 1998, Fitton & Goa 1991, Passi et al. 1989). Its exact mechanism is unknown.
Literature References
PubMed ID Title Journal Year
19936164 Therapeutic options in the treatment of benign prostatic hyperplasia

Sandhu, JS

Patient Prefer Adherence 2009
3207614 Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid

Stamatiadis, D, Mowszowicz, I, Bulteau-Portois, MC

Br J Dermatol 1988
1712709 Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders

Goa, KL, Fitton, A

Drugs 1991
2534550 [Mechanism of azelaic acid action in acne]

Nazzaro-Porro, M, Picardo, M, Passi, S, De Luca, C

G Ital Dermatol Venereol 1989
18318566 Dutasteride: a review of its use in the management of prostate disorders

Keam, SJ, Scott, LJ

Drugs 2008
9871428 A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors GI198745 and finasteride

Karlsson, MO, Hammarlund-Udenaes, M, Gisleskog, PO, Hermann, D

Clin Pharmacol Ther 1998
1279965 Finasteride for benign prostatic hyperplasia

Rose, LI, Hasinski, S, Miller, JL

Am Fam Physician 1992
3783591 Azasteroids: structure-activity relationships for inhibition of 5 alpha-reductase and of androgen receptor binding

Walton, E, Steinberg, NG, Rasmusson, GH, Cascieri, MA, Liang, T, Patel, GF, Cheung, AH, Reynolds, GF, Brooks, JR, Berman, C

J Med Chem 1986
19879888 An overview on 5alpha-reductase inhibitors

Kumar, M, Bhardwaj, TR, Aggarwal, S, Verma, A, Thareja, S

Steroids 2010
25961201 Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride

Yamana, K, Luu-The, V, Labrie, F

Horm Mol Biol Clin Investig 2010
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