Discovery of how a protein called SMAD3 behaves has given new insights into puberty development in boys and fertility in adult men; the researchers also hope it will lead to a better understanding of how chemicals in the environment affect these processes.

You can read about the findings in a paper published in the 8 March online issue of Endocrinology.

Around 1 in 10,000 boys go through early or “precocious” puberty at around eight years of age.

Altered timing of puberty affects adulthood, with early puberty linked to reduced adult height and delayed puberty linked to reduced bone density.

Late puberty occurs when the testes or testicles, the part of the male organ that produces sperm, cannot respond normally to testosterone.

First author Dr Catherine Itman, from the Faculty of Medicine, Nursing and Health Sciences at Monash University in Melbourne, Australia, told the press they have been looking at the effect of SMAD3 on the growth of testis or testicle cells and how they respond to testosterone:

“SMAD3 is a protein that translates signals from the environment outside the cell to the nucleus, where it switches genes on or off,” she added.

The crucial part of the discovery appears to lie in the rate at which SMAD3 is produced: half the normal amount leads to faster maturation than usual, and none at all leads to abnormal responses to testosterone.

For their study, the researchers focused on Sertoli cells, the “nurse” cells that help the testes or testicles to mature.

Male puberty begins when the body starts to produce large amounts of the hormone testosterone, and this acts through the Sertoli cells.

The researchers already knew that before puberty, Sertoli cells multiply and this helps the testes to grow, and at puberty, Sertoli cells have to stop growing in order to then help the testes produce sperm by supporting the growth of sperm precursor cells.

Thus, the establishment and maturation of the Sertoli cell population in the testicles underpins male fertility.

Itman and colleagues investigated how Sertoli cells switch from the multiplying state, that results in making the testes big enough to make sperm, to the mature state, that helps to produce the sperm.

Using laboratory mice, they identified that Sertoli cell activity before and after puberty depended on the amount of SMAD3 that was present, such that when it is reduced, sperm develops earlier, and when it is absent altogether, the Sertoli cells take longer to respond to testosterone.

So, contrary to previous understanding, it was not a case of an “on-off” switch, but rather a dependence on the amount of SMAD3 protein, which was different in the immature, multiplying Sertoli cell compared to the mature, adult cell.

Other research on puberty has also proposed that development is delayed in boys exposed to chemicals that disrupt how cells respond to hormones.

These so-called “endocrine disrupting compounds” are widely used in industries that make everyday items like plastics, cosmetics, paints and detergents.

Itman’s work is funded by a grant from the National Health and Medical Research Council (NHMRC) Early Career Project to look into how these compounds in the environment affect the growth and maturation of Sertoli cells around puberty, including the role of SMAD3.

“We hope that through our research, we will inform decisions about the influence of chemicals in our environment on the timing of puberty in boys and on the fertility of adult men,” said Itman.

“Smad3 Dosage Determines Androgen Responsiveness and Sets the Pace of Postnatal Testis Development.”
Catherine Itman, Chin Wong, Briony Hunyadi, Matthias Ernst, David A. Jans, and Kate L. Loveland.
Endocrinology, published 8 March 2011

Additional source: Monash University.

Written by: Catharine Paddock, PhD