The backdoor pathway to dihydrotestosterone

Abstract

Dihydrotestosterone (DHT) is the androgen responsible for formation of the male external genitalia during embryogenesis and for most androgen-mediated events at male puberty. In most circumstances, testosterone (T) derived from the testis is converted to DHT by 5alpha-reductase type 2 in genital skin and prostate. By contrast, the testes of pouch young of the tammar wallaby and immature postnatal testes of several species synthesize 5alpha-androstane-3alpha,17beta-diol, which is the proximal precursor of DHT in androgen-target tissues. Human steroidogenic enzymes efficiently catalyze all the required steps in a route to DHT that does not involve the T intermediate, called the 'backdoor pathway'. This alternative pathway of DHT production appears to explain how potent androgens are produced in some normal and pathological conditions when the conventional androgen-biosynthetic pathways fail to account completely for the of patterns androgen synthesis that are observed.