Melbourne, Australia. Scientists have discovered that an inability to create SMAD3 gene protein results in abnormal responses to testosterone, while just half as much of the usual protein amount results in faster male maturation.

The finding uncovers a new understanding of how male puberty begins and what can happen when non-standard regulation of the SMAD3 protein production rate occurs. It also raises questions about an equivalent role for female puberty.


The SMAD family of proteins is part of the TGFß superfamily of gene modulators, well known for its role in nonreproductive tissues. The family is one of several human homologues of a gene which was originally discovered in the fruit fly Drosophila melanogaster. SMAD3 is a family member that translates signals from the environment outside the cell to the nucleus, where it switches genes on or off.

SMAD3 and Female Maturation

The primary focus of this research was on male maturation.

Previous research has shown that SMAD3 alters female fertility and regulates the growth and survival of ovarian follicles.

The growth regulation is highly indicated even though it may not affect the size of the primordial follicle pool at birth.

The results suggest an important role for SMAD3 in the regulation of ovarian follicle growth and female fertility.

The full activation picture in either sex remains uncertain, but can so far can be viewed as the consequence of upstream processes closer to conception.

This could explain how changing ratios of the protein amounts in both sexes could alter the standard scenarios for puberty.

For example, there is a potential for mismatched expectations where an anatomical male has the regulatory mechanisms for female puberty and vice versa.

The human body has an elaborate set of repair procedures to keep the body going, and even procreate, with equipment that may not be optimal for the job.Puberty begins when the body starts to produce large amounts of the hormone testosterone. Early, or precocious, puberty involves the onset of puberty before eight years of age and affects around 1 in 10,000 boys.

SMAD3, Testis Cells and Testosterone Response

On the other hand, puberty is delayed when testis cells cannot respond normally to testosterone. Altered timing of puberty has implications in adulthood, with precocious puberty linked to reduced adult height and delayed puberty associated with reduced bone density.

Testosterone acts through specialized cells in the testis called Sertoli cells. Before puberty, Sertoli cells multiply, allowing the testis to grow. At puberty, Sertoli cells must stop growing so they can support sperm precursor cells to develop into sperm.

Associate Professor Kate Loveland and Dr Catherine Itman from the Faculty of Medicine, Nursing and Health Sciences, both from Monash University published the results with their colleagues in the journal Endocrinology.

Loveland, Itman and their colleagues have been investigating how Sertoli cells switch from a multiplying state, making the testis big enough to make sperm, to a mature state that sustains sperm production.

The research identified that it is the actual amount of SMAD3 present that controls Sertoli cell activity prior to, or after, puberty.

No On/Off Switch

It is the amount of the SMAD3 protein in the Sertoli cell that is different in the immature, multiplying Sertoli cell compared to the mature, adult cell. When SMAD3 levels are reduced, sperm develop earlier. When SMAD3 is absent, Sertoli cells take longer to respond to testosterone.

Previous research on puberty suggests that pubertal development is delayed in boys exposed to endocrine disrupting compounds, chemicals which impair cell responses to hormones. These chemicals are widely used in industry and in the manufacture of everyday items, such as plastics, cosmetics, paints and detergents.

Dr Itman current work investigates how these hormone-disrupting chemicals in the environment affect the growth and maturation of Sertoli cells around puberty, including changes to SMAD3 levels and activity.

“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” Dr Itman said.

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