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Alternative (backdoor) androgen production and masculinization in the human fetus

Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis...

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Published in:PLoS biology 2019-02, Vol.17 (2), p.e3000002-e3000002
Main Authors: O'Shaughnessy, Peter J, Antignac, Jean Philippe, Le Bizec, Bruno, Morvan, Marie-Line, Svechnikov, Konstantin, Söder, Olle, Savchuk, Iuliia, Monteiro, Ana, Soffientini, Ugo, Johnston, Zoe C, Bellingham, Michelle, Hough, Denise, Walker, Natasha, Filis, Panagiotis, Fowler, Paul A
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Language:English
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Summary:Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human fetuses using multidimensional and high-resolution mass spectrometry. Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3000002