Testosterone is not the only hormone needed for penis development

A new study has revealed that testosterone, which is produced and released by the testes, is not the only hormone involved in fetal development of the male penis. It is now thought that the masculinization process also involves a hormone called androsterone, which originates in other tissues, including the placenta.

Fetus in the wombSebastian Kaulitzki | Shutterstock

The results not only shed light on a previously unknown “backdoor” pathway of masculinization, but could also explain the link between placental dysfunction and disorders of male genital development.

These insights have the potential to make a big difference to how we treat sexual disorders in male babies in future – and are also relevant to the whole debate about male and female identity.

Paul Fowler, Study Author.

During male fetal development, testosterone from the testes is converted into the male sex hormone 5α-dihydrotestosterone (DHT) by the genital tubercle – the primordial structure that either develops into a penis or clitoris.

In one in a few thousand cases, babies are born with “ambiguous” genitalia, where their gender is not quite clear. Previously, the understanding was that this is caused by problems associated with testosterone.

However, recent studies have shown that penis development also relies on a second, alternative or “backdoor” pathway, where DHT is produced independently of testosterone from the testicles. However, the details of this other pathway remained unclear, including the source DHT.

As reported in the journal PLOS Biology, Fowler and collaborators in Glasgow, France and Sweden have conducted a study that explains more about this second process.

Using mass spectrometry, the team measured levels of steroid hormones in fetal plasma and tissue during the second trimester - the most vital phase for penis development. The researchers also measured gene expression in tissues known to be involved in hormone synthesis.

The study revealed that the hormone androsterone, which can also be converted to DHT, was the main steroid hormone present in the blood of the male fetus and that both androsterone and testosterone were present at lower levels in the female circulation.

In addition, the enzymes required to convert androsterone to DHT were mainly present in non-gonadal tissues including the placenta and the liver.

Given that androsterone can be made from progesterone, Fowler and colleagues suggest that placental progesterone is the androsterone source in the alternative pathway.

Our results demonstrate that masculinization of the male fetus depends not only on the testes, but also on other tissues, especially the placenta. 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.”

Sally Robertson

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Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.

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