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
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
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
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
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
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