Penis development needs more than just testes and testosterone: ‘Backdoor’ pathway to masculinity involves androsterone from multiple tissues, including the placenta


During development of the male fetus, the testes release testosterone, a steroid hormone which is converted to 5?-dihydrotestosterone (DHT) by the genital tubercle, helping to ensure that this primordial structure develops into a penis, rather than into the female clitoris. Recently, penis development was shown to also depend on a second process, called the alternative or “backdoor” pathway, which also ends in the production of DHT but doesn’t depend on the production of testosterone by the testes. However, the details of this backdoor pathway, including the source of the DHT precursor, have been unclear.

To learn more about this pathway, the authors used mass-spectrometry to measure levels of different steroids in fetal plasma and tissue during the second trimester, when the most critical steps in penis development occur. They also analyzed gene expression levels in various tissues of key enzymes known to be involved in hormone synthesis.



“Our results demonstrate that masculinization of the male fetus depends not only on the testes, but also on other tissues, especially the placenta” Fowler and Bellingham said. “They also suggest an explanation for why disorders of placental insufficiency can lead to hypospadias and other abnormalities of growth of the male external genitalia.”

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