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.

The conversion of testosterone to the most potent androgen, 5-alpha-dihydrotestosterone (DHTEST), is catalyzed by microsomal 5alpha-steroid reductase 2, (SRD5A2) (Andersson et al. 1991). SRD5A2 is highly expressed in the prostate but also in other androgen target sites. Defects in SRD5A2 are the cause of pseudovaginal perineoscrotal hypospadias, also known as male pseudohermaphroditism (Anwar et al. 1997). Corticotropin (Adrenocorticotropic hormone, ACTH) acts through the ACTH receptor called melanocortin receptor type 2 (MC2R) to stimulate steroidogenesis, increasing the production of androgens (McKenna et al. 1997).