Penis development needs more than just testes and testosterone

Immunofluorescence image of a human fetal adrenal gland showing the steroid cells. / Zoe Johnston

The masculinization in the human fetus is not only the result of testosterone manufactured by the testes. A new study published in PLOS Biology confirms that the fetal development of the penis also requires other hormones, such as androsterone, produced by the placenta and other organs.

In addition to the role of testosterone, European researchers have identified for the first time the details of an 'alternative' biological process that is necessary to develop the male genitalia in a fetus .


The findings, published in the journal PLOS Biology , also shed more light on the reasons why babies are born with undescended testes, malformations in the penis and other anomalies of the male external genitalia.

This work shows for the first time that the placenta and the adrenal gland are also involved in the development of male genitalia

During the development of the male fetus, the testes release testosterone , a steroid hormone produced by the testes that is converted to 5α-dihydrotestosterone (something like a 'supertestosterone' called DHT ), which ensures the formation of a penis instead of a clitoris female.

This new work, led by scientists from the universities of Aberdeen (United Kingdom) and Glasgow (Scotland), shows for the first time that the placenta and the adrenal gland are also involved in the creation of said 'supertestosterone'.

The results reveal a previously unknown pathway of masculinization of the external genitalia that may explain why placental dysfunction is associated with disorders of male genital development . Both processes must occur successfully to ensure that the male genitalia develop normally.

"There are two ways to produce DHT: through the testosterone of the testicles and through a different set of hormones produced by other organs, including the adrenal gland of the fetus and the placenta," explains Michelle Bellingham of the University of Glasgow. .

"In humans, both routes have to work correctly for a male fetus to become a male baby. We know that male fetuses whose placentas function poorly are much more likely to be born with undescended testes or malformed penises. Now we understand why, "he adds.

Optimize diagnosis and treatment

The findings themselves will not lead directly to new treatments, but will increase the chances of developing new strategies for early diagnosis and correction of poor masculinization.

The authors found that androsterone , a steroid hormone from the 'alternative' pathway, can also become DHT. They also found that the enzymes needed for said pathway were present mainly in the non-gonadal tissue , including those of the liver and the placenta.

Normally the penis is completely formed at the beginning of the second trimester and increases in size during adolescence

In addition, they found that the levels of both androsterone and testosterone were lower in the fetal circulation of future girls.

"If markers of placental dysfunction are obtained around the synthesis of steroid hormones, then there will be a greater probability of detection and treatment for correction or supplementation of such abnormalities, " explains Paul Fowler, of the University of Aberdeen.

Normally the penis is completely formed at the beginning of the second trimester and increases in size during adolescence. "What we now know is that the testicles alone are not enough to do this in humans and that the hormones produced by the placenta are equally essential," he continues.

Some people affected by sexual development disorders may encounter difficulties as they grow up or need to face difficult surgery and long-term hormone therapy. "Every new information on how masculinization occurs helps us understand how to detect and treat these disorders," concludes Fowler.

Bibliographic reference:  O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, et al. (2019) Alternative (backdoor) androgen production and masculinization in the human fetus. PLoS Biol 17 (2): e3000002. https://doi.org/10.1371/journal.pbio.3000002