5α-Reductase inhibitors (5-ARIs) are a class of chemicals with antiandrogen effects, used primarily in the treatment of benign prostatic hyperplasia (BPH) (enlarged prostate) and androgenic alopecia (pattern hair loss). They are also used less commonly to treat hirsutism (excessive hair growth) in women. These agents inhibit the enzyme 5α-reductase, which is involved in the metabolic transformations of a variety of endogenous steroids. 5α-reductase inhibition is most known for preventing conversion of testosterone, the major androgen sex hormone, to the more potent dihydrotestosterone (DHT), in androgen-associated disorders.
An Overview of 5α-Reductase
5α-Reductase is an important enzyme in the process of androgen metabolism. 5α-Reductase can convert testosterone into more active dihydrotestosterone, which is widely involved in the metabolism of androgen in the body and plays an important physiological role. The 5α-Reductase is present on the microsomes and is a reduced nicotinamide adenine dinucleotide phosphate-dependent membrane protease.
Major type of 5α-Reductase
The human 5α-Reductase have two isoenzymes: 5α-Reductase type 1 (5α-R1) and 5α-reductase type 2 (5α-R2). 5α-R1 is present in the liver, lung and non-genital parts of the skin and its appendages, while 5α-R2 is mainly found in the prostate, seminal vesicles and inner root sheaths. These two isozymes are encoded by RD5A1 and SRD5A2, respectively. Both genes are composed of 5 exons and 4 introns. SRD5A1 is located on chromosome 5p15 and SRD5A2 is located on chromosome 2p23. 5α-R1 and 5α-R2 have approximately 50% homology in amino acid composition. 5α-R2 has a greater affinity with substrates (such as Testosterone and Finasteride) than 5α-R1.
Inhibition of 5α-Reductase
At present, a variety of 5α-Reductase inhibitors have been developed and have achieved good therapeutic effects in the treatment of diseases associated with androgen increase, such as Testosterone, Finasteride, Dutasteride and Iridamide. In addition, it has been reported that 5α-Reductase inhibitors combined with adrenergic antagonists for benign prostatic hyperplasia have a better therapeutic effect than 5α-Reductase alone. This suggests that combination therapy will open up a broader world for the future treatment of 5α-Reductase-related diseases.
5α-Reductase and diseases
Defects in 5α-Reductase can lead to abnormalities in local tissue or orthologous levels, leading to a variety of diseases such as acne, androgenetic alopecia, polycystic ovary syndrome, and male pseudohermaphroditism. 5α-Reductase is involved in androgen metabolism in the body and is associated with systemic multisystem diseases. In patients with 5α-Reductase deficiency, several diseases or syndromes often coexist. Inhibition of 5α-Reductase activity has become a therapeutic target for some diseases.
Russell D.W., Wilson J. D. (1994) Steroid 5alpha-Reductase: Two Genes/Two Enzymes. Annu Rev Biochem. 63 (1): 25-61.