Higher rates of Autism Spectrum Disorders in males than females may be related to changes in the brain’s estrogen signalling, according to a new study led by an Indian-origin scientist.

The study examined the brains of people that had Autism Spectrum Disorders compared to controls, and found that they are linked with far lower levels of a key estrogen receptor and other estrogen-related proteins.

Because of the small group size, these results indicate an exciting avenue for further research, rather than confirming a role for altered estrogen signalling in Autism Spectrum Disorders.

“Our study is the first indicator that estrogen receptors in the brain of Autism Spectrum Disorder patients may be different to controls. Though this suggests a possible reason for the gender bias, we still need to determine what causes the reduced production of estrogen-related proteins,” said Anilkumar Pillai, lead author.

Autism Spectrum Disorders are a group of disorders that affect brain development, and are commonly recognised by impaired social interaction, verbal and non-verbal communication, and restricted and repetitive behaviour.

The disorders appear to have a genetic basis and are around four times more common in men than in women.

Autism Spectrum Disorders have been associated with higher levels of the sex hormone testosterone, but whether there is a relationship between the disorders and estrogen signalling was not known.

A group of researchers from Georgia Regents University measured the expression of proteins involved in the estrogen signalling pathway in brain tissue from 13 people that had Autism Spectrum Disorders and 13 controls.

The low numbers involved in the study are because brain tissue for experimental use from individuals that had Autism spectrum Disorders is quite scarce.

They looked for levels of ER beta - an estrogen receptor molecule, and aromatase, an enzyme which converts testosterone to estradiol, the most potent estrogen.

They found 35 per cent less ER beta mRNA and 38 per cent less aromatase mRNA in autistic brain tissue in comparison with controls. They also found much less of the mRNA of estrogen receptor co-factors.

The lower levels of estrogen receptors and aromatase could lead to reduced conversion of testosterone to estradiol, resulting in increased levels of testosterone.

“It is worth looking at whether drugs which modulate estrogen reception, but do not cause feminisation, could allow for the long-term treatment of male patients with Autism Spectrum Disorders,” Pillai said. The study was published in the journal Molecular Autism.

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