Backdoor pathway for dihydrotestosterone biosynthesis: Implications for normal and abnormal human sex development

Maki Fukami, Keiko Homma, Tomonobu Hasegawa, Tsutomu Ogata

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


We review the current knowledge about the "backdoor" pathway for the biosynthesis of dihydrotestosterone (DHT). While DHT is produced from cholesterol through the conventional "frontdoor" pathway via testosterone, recent studies have provided compelling evidence for the presence of an alternative "backdoor" pathway to DHT without testosterone intermediacy. This backdoor pathway is known to exist in the tammar wallaby pouch young testis and the immature mouse testis, and has been suggested to be present in the human as well. Indeed, molecular analysis has identified pathologic mutations of genes involved in the backdoor pathway in genetic male patients with undermasculinized external genitalia, and urine steroid profile analysis has argued for the relevance of the activated backdoor pathway to abnormal virilization in genetic females with cytochrome P450 oxidoreductase deficiency and 21-hydroxylase deficiency. It is likely that the backdoor pathway is primarily operating in the fetal testis in a physiological condition to produce a sufficient amount of DHT for male sex development, and that the backdoor pathway is driven with a possible interaction between fetal and permanent adrenals in pathologic conditions with increased 17-hydroxyprogesterone levels. These findings provide novel insights into androgen biosynthesis in both physiological and pathological conditions. Developmental Dynamics 242:320-329, 2013.

Original languageEnglish
Pages (from-to)320-329
Number of pages10
JournalDevelopmental Dynamics
Issue number4
Publication statusPublished - 2013 Apr


  • 21-OH deficiency
  • Backdoor pathway
  • Dihydrotestosterone
  • Disorders of sex development
  • P450 oxidoreductase deficiency
  • Testosterone

ASJC Scopus subject areas

  • Developmental Biology


Dive into the research topics of 'Backdoor pathway for dihydrotestosterone biosynthesis: Implications for normal and abnormal human sex development'. Together they form a unique fingerprint.

Cite this