Penis development needs more than just testes and testosterone

February 14, 2019, Public Library of Science
An immunofluorescence image of a human fetal adrenal gland showing the steroidogenic cells. Credit: Zoe Johnston

Proper development of the fetal penis requires not just testosterone from the testes, but a second hormone produced by other tissues, including the placenta, according to a new study publishing February 14 in the open-access journal PLOS Biology from Paul Fowler of the University of Aberdeen, Michelle Bellingham of the University of Glasgow, and colleagues in the UK, France and Sweden. The results reveal a previously unknown pathway of masculinization of the external genitals, and may explain why placental dysfunction is associated with disorders of male genital development.

During development of the male fetus, the testes release , a which is converted to 5α-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" , 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 during the , when the most critical steps in penis development occur. They also analyzed in various tissues of key enzymes known to be involved in hormone synthesis.

They found that androsterone, a steroid from the backdoor pathway, which can be converted to DHT, was the principal androgen in the male fetal circulation, and that levels of both androsterone and testosterone were lower in the female fetal circulation. They also found that enzymes needed for the backdoor pathway were present primarily in non-gonadal tissue, including the liver and the placenta.

Since androsterone can be made from progesterone, the authors suggest that placental progesterone or related compounds are the likely source of androsterone in the backdoor pathway. While it remains unclear why a sex difference in fetal androsterone levels exists, the authors found high expression in the male genital tubercle of enzymes required to convert androsterone to DHT. The male genital tubercle appears, therefore to be able to convert both testosterone and androsterone into DHT.

"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."

Explore further: 3-D ultrasound not accurate for ID of sex in first trimester

More information: O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan M-L, Svechnikov K, Söder O, et al. (2019) Alternative (backdoor) androgen production and masculinization in the human fetus. PLoS Biol 17(2): e3000002.

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2.1 / 5 (9) Feb 14, 2019
Don't tell the #MeToo Pussy-hat wearing bowel movement about this, or they might take steps to ensure that the foetus won't be allowed to develop male genitalia. Scientific research is often frightening.
3.3 / 5 (6) Feb 14, 2019
You know, hating men and hating being raped by men are different things. Are you sticking up for rapists, is that where we are at with internet morons now? "The earth is flat, climate change is a fantasy, and rape is totally okay." - Surveillance_egg_unit 2019
2.3 / 5 (3) Feb 15, 2019
Are you aware of how stupid you sound with such an idiotic comment? Where did I say that I was sticking up for rapists? Or are you just making shit up as you go because you can?
US Supreme Court Justice Kavanaugh was accused of raping teenaged girls when he was in high school, by 2 women who told lies about him for the purpose of preventing him being appointed to the Supreme Court. It was found that because Kavanaugh is a Conservative, these women were afraid that he would work to rule against abortions. And it turned out that the women were lying about him. Perhaps you know of that case?
There have been many other false accusations of men raping women that were found to be lies.
When there is justification and corroboration by credible witnesses regarding the rape, then the law should be followed and justice meted out to the perpetrator. But innocent men have been accused and their lives destroyed by women whose goal was for some sort of revenge.
2.3 / 5 (3) Feb 15, 2019
So, you are a "Flat-Earther? Do you have evidence for the Earth being flat? I suppose you also don't believe in evolution. Why are you commenting in a science website anyway?

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