Estrogen Receptor Expression Could Explain Why Males Are More Likely To Have Autism

Chuck Bednar for redOrbit.com – Your Universe Online
The reason that girls are less likely than boys to suffer from autism may have something to do with the same sex hormone receptor responsible for helping protect them from stroke, according to new research published Tuesday in the journal Molecular Autism.
In what is being called the first analysis of the role of estrogen in autism, experts from the Medical College of Georgia at Georgia Regents University examined the brains of people with autism spectrum disorders (ASD) and compared them to control subjects. They found that ASD was associated with far lower levels of estrogen receptor beta.
Estrogen receptor beta, which enables estrogen’s ability to protect the brain, also plays a role in locomotion and a variety of behaviors, including anxiety, depression, memory and learning. Furthermore, the study authors also said that subjects diagnosed with autism also had significantly reduced levels of other estrogen-related proteins.
“If you ask any psychiatrist seeing patients with autistic behavior their most striking observation from the clinic, they will say there are more males compared to females,” corresponding author and neuroscientist Dr. Anilkumar Pillai said in a statement, adding that his team’s research “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,” he added. “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… However, additional studies are needed to test the estrogen mechanism.”
According to the study authors, this might help explain why males are five times more likely than females to be autistic. Estrogen is known to help prevent stroke and cognitive decay in premenopausal women, while exposure to high levels of the male sex hormone testosterone during early stages of development has been linked to ASD.
In addition to reduced expression of estrogen receptor beta in the brains of autism patients, the study authors found less of an enzyme that helps convert testosterone to estrogen. Dr. Pillai believes that this discovery could help explain why autistic individuals tend to have higher testosterone levels, as well as why men have higher autism rates.
“The testosterone hypothesis is already there, but nobody had investigated whether it had anything to do with the female hormone in the brain,” he explained. “Estrogen is known to be neuroprotective, but nobody has looked at whether its function is impaired in the brain of individuals with autism. We found that the children with autism didn’t have sufficient estrogen receptor beta expression to mediate the protective benefits of estrogen.”
Their comparison of children with and without ASD revealed a 35 percent decrease in estrogen receptor beta expression and a 38 percent reduction in the amount of aromatase, the enzyme that converts testosterone to estrogen, the investigative team reported. In addition, levels of estrogen receptor beta proteins (active molecules resulting from gene expression that enables functions such as brain protection) were also lower.
No discernible difference was found in the expression levels of estrogen receptor alpha, which mediates sexual behavior, the Medical College of Georgia researchers found. Their analysis focused on the prefrontal cortex – the region of the brain in social behavior and cognition – and used brain tissue obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders.
Dr. Pillai said that estrogen receptor beta agonists, which have already been demonstrated to improve brain plasticity and memory in animals, could ultimately be used to help reverse some of the symptoms of autism, such as reclusiveness and repetitive behavior.
He and his colleagues plan to begin animal studies to see what affect reducing estrogen receptor beta expression has on mice by giving an estrogen receptor beta agonist to a rodent showing signs of autistic behavior. Future, larger-scale trials could also compare the expression of testosterone receptor levels in healthy and autistic children, the scientists said. They are also curious as to why the reduced beta receptor expression occurs.

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