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

Biason-Lauber, Anna; Miller, Walter L; Pandey, Amit V; Flück, Christa E (2013). Of marsupials and men: "Backdoor" dihydrotestosterone synthesis in male sexual differentiation. Molecular and cellular endocrinology, 371(1-2), pp. 124-32. Shannon: Elsevier Ireland 10.1016/j.mce.2013.01.017

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Following development of the fetal bipotential gonad into a testis, male genital differentiation requires testicular androgens. Fetal Leydig cells produce testosterone that is converted to dihydrotestosterone in genital skin, resulting in labio-scrotal fusion. An alternative 'backdoor' pathway of dihydrotestosterone synthesis that bypasses testosterone has been described in marsupials, but its relevance to human biology has been uncertain. The classic and backdoor pathways share many enzymes, but a 3α-reductase, AKR1C2, is unique to the backdoor pathway. Human AKR1C2 mutations cause disordered sexual differentiation, lending weight to the idea that both pathways are required for normal human male genital development. These observations indicate that fetal dihydrotestosterone acts both as a hormone and as a paracrine factor, substantially revising the classic paradigm for fetal male sexual development.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Flück, Christa




Elsevier Ireland




Factscience Import

Date Deposited:

04 Oct 2013 14:40

Last Modified:

06 Dec 2013 13:38

Publisher DOI:


PubMed ID:


Web of Science ID:



https://boris.unibe.ch/id/eprint/16088 (FactScience: 223663)

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