SRD5A2 binds SRD5A2 inhibitors

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).<br><br>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.<br><br>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.

睾酮（TEST）转化为最强效的雄激素——5-α-二氢睾酮（DHTEST）的过程，由微体5α-类固醇还原酶1-3（SRD5A1-3）催化。SRD5As在前列腺、皮肤及其他雄激素靶组织中高度表达。良性前列腺增生（BPH）是一种可能导致男性出现下尿路症状（LUTS）的病理过程。BPH指的是环绕尿道的前列腺区域发生的间质和腺体上皮的增生，这一过度生长主要依赖于雄激素，特别是DHTEST。鉴于SRD5As负责DHTEST的生成，SRD5A抑制剂可应用于治疗伴有症状的BPH（Rasmusson等，1986年；Gisleskog等，1998年）。

已批准用于治疗BPH的阿扎司特类固醇有非那雄胺和度他雄胺（Sandhu，2009年）。度他雄胺能够阻断所有三种SRD5A异构体，并且可以将血液中的DHTEST水平降低至高达98%（Keam & Scott，2008年；Yamana等，2010年）。相比之下，非那雄胺（Hasinki等，1992年）仅抑制II型和III型同工酶，因此只能将循环中的DHTEST水平降低至65至70%（Yamana等，2010年；Aggarwal等，2010年）。然而，这两种药物均能使前列腺腺体内的DHTEST水平降至相似程度，其中SRD5A2异构体占主导地位。

二羧酸类阿扎酸是人体皮肤中SRD5A的强效抑制剂，有望成为治疗与雄激素相关的人类皮肤病理状态（如各种类型的痤疮和皮肤色素沉着过度障碍）的有效药剂（Stamatiadis等，1998年；Fitton & Goa，1991年；Passi等，1989年）。其确切作用机制尚不明确。