Estrogen, Mistakenly Believed A Female-Only Hormone, May Be Key To Why Autism Rates Are Higher In Boys

autism
The higher rate of autism spectrum disorders may be related to changes in the brain's estrogen signaling, suggesting a potential new drug target. Reuters

Autism spectrum disorders (ASD) are a range of neurodevelopment conditions characterized by social impairment, communication difficulty, and restricted and repetitive patterns of behavior. Although a great deal is unknown about ASD, what is known is that it is much more common in boys. In fact, autism is about four times more common in boys than girls, and now, a team of researchers, who conducted a new study at Georgia Regents University, say this higher rate may be related to changes in the brain's estrogen signaling. "It is worth looking at whether drugs which modulate estrogen reception, but do not cause feminization, could allow for the long-term treatment of male patients with Autism Spectrum Disorders,” said Dr. Anilkumar Pillai, a professor in the department of psychiatry and lead author of the study.

Investigating the Link between ASD and Sex Hormones

While autism disorders appear to have a genetic basis, research suggests autism may also be linked to sex hormones. For instance, a recent European study found babies who later develop autism had been exposed to higher levels of testosterone while in the womb. This finding led scientists to question whether there might be a relationship between the disorder and estrogen, which is often mistakenly thought of as a female hormone but is also produced in males.

To understand whether estrogen might be linked to the higher rate of ASD in boys, a group of researchers from Georgia Regents University examined brain tissue samples from 13 deceased people who had ASDs and compared them to samples from 13 controls. In particular, the research team measured the expression of proteins involved in the estrogen signaling pathway: ERβ, an estrogen receptor molecule, and aromatase, an enzyme which converts testosterone to estradiol.

Compared to controls, autistic brain tissue had 35 percent less ERβ expressed and 38 percent less aromatase expressed, while also showing diminished expression of two estrogen receptor co-factors. The researchers speculate that these lower levels of an estrogen-related receptor and proteins might lead to the reduced conversion of testosterone to estradiol, which in turn could result in increased levels of testosterone.

“Current treatment involves the use of antipsychotics, which has long been a major concern as these patients are typically still in a stage of life where brain development is very rapid,” Pillai said. “However, additional studies are needed to test the estrogen mechanism.” Because of the small group size, the researchers caution their results cannot confirm a role played by altered estrogen signaling, but still, the outcome of the study suggests an exciting path for further investigation.

Source: Crider A, Thakkar R, Ahmed AO, Pillai A. Dysregulation of Estrogen Receptor beta (ERbeta), Aromatase (CYP19A1) and ER Co-activators in the middle frontal gyrus of autism spectrum disorder subjects. Molecular Autism. 2014.

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