The backdoor pathway to dihydrotestosterone

@article{Auchus2004TheBP,
  title={The backdoor pathway to dihydrotestosterone},
  author={Richard J. Auchus},
  journal={Trends in Endocrinology \& Metabolism},
  year={2004},
  volume={15},
  pages={432-438},
  url={https://api.semanticscholar.org/CorpusID:10631647}
}
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341 Citations
Highly Influential Citations
23
Background Citations
118
Methods Citations
7
Results Citations
2

341 Citations

Clinical implications of androgen synthesis via 5alpha-reduced precursors.

An alternate pathway to DHT was elucidated in the tammar wallaby pouch young, and studies in knockout mice showed that this pathway uses 5alpha-reductase type 1 to convert 17-hydroxyprogesterone to 5 alpha-reduced androgen precursors.

Of marsupials and men: “Backdoor” dihydrotestosterone synthesis in male sexual differentiation

Classic and backdoor pathways of androgen biosynthesis in human sexual development

Findings are essential to understanding human sexual development, as androsterone was found to be the primary androgen of the human backdoor route and steroidal substrates specific to the backdoor route are predominantly found in the placenta, liver, and adrenal glands rather than in the testes.

Alternative pathway androgen biosynthesis and human fetal female virilization

It is shown that adrenals and genital skin cooperate to produce androgens via the alternative pathway during the major period of human sexual differentiation and that neonates with PORD still produce alternative pathway androgens during the first weeks of life, which indicates that alternative pathways androgen biosynthesis drives prenatal virilization in CAH due to PORD.

Marsupial pathway in humans

The “backdoor pathway” of androgen synthesis in human male sexual development

It is shown that the principal human backdoor androgen is androsterone and provided strong evidence that it derives from placental progesterone that is metabolized to androstersone in nontesticular tissues, essential to understanding human sexual development and its disorders.

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

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 thebackdoor pathway is driven with a possible interaction between fetal and permanent adrenals in pathologic conditions with increased 17‐hydroxyprogesterone levels.

Androgen production in pediatric adrenocortical tumors may occur via both the classic and/or the alternative backdoor pathway

Basics of androgen synthesis and action.

The human genital tubercle is steroidogenic organ at early pregnancy

...

38 References

Prostate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol

It is shown that the 3α-reduced derivative of DHT, 5α-androstane-3α,17β-diol (5α-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation, suggesting that circulating 5α -adiol is a key hormone in male development.

Opposing changes in 3alpha-hydroxysteroid dehydrogenase oxidative and reductive activities in rat leydig cells during pubertal development.

It is hypothesized that in Leydig cells, differential expression of 3alpha-HSD enzymes favoring one of the two directions is a mechanism by which DHT levels are controlled and may account for the resultant high capacity of Leydenig cells on Day 90 to synthesize DHT from 3 alpha-DIOL.

Testicular steroid metabolism during development in the normal and hypogonadal mouse.

The patterns of testicular steroidogenesis were investigated during postnatal development in the normal mouse and in the hypogonadal mouse from 20 days, with a marked decrease in steroid metabolism, with androstenedione (the major androgen) being formed mainly through the delta 4 pathway.

Testosterone formation and metabolism during male sexual differentiation in the human embryo.

It was concluded that testosterone is the principal androgen formed by the fetal testis at the time of male sexual differentiation.

The marsupial model for male phenotypic development

Steroid 5α-reductase 1 promotes 5α-androstane-3α,17β-diol synthesis in immature mouse testes by two pathways

5α-androstane-3α, 17β-diol is formed in tammar wallaby pouch young testes by a pathway involving 5α-pregnane-3α, 17α-diol-20-one as a key intermediate

It is concluded that expression of steroid 5 α-reductase in the developing wallaby testes allows formation of 5α-reduced androgens by a pathway that involves the formation of testosterone and dihydrotestosterone as intermediates.

The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway.

The majority of testosterone biosynthesis in the human testis proceeds through the conversion of pregnenolone to dehydroepiandrosterone via the delta(5) pathway.

Apparent pregnene hydroxylation deficiency (APHD): seeking the parentage of an orphan metabolome

Metabolic pathways for androstanediol formation in immature rat testis microsomes.