Researchers reveal first autism candidate gene that demonstrates sensitivity to

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Researchers reveal first autism candidate gene that demonstrates sensitivity to

sex hormones

February 16, 2011

Washington University researcher, Dr. Hu, Professor of

Biochemistry and Molecular Biology, and her team at the School of Medicine and

Health Sciences, have found that male and female sex hormones regulate

expression of an important gene in neuronal cell culture through a mechanism

that could explain not only higher levels of testosterone observed in some

individuals with autism, but also why males have a higher incidence of autism

than females.

The gene, RORA, encodes a protein that works as a " master switch " for gene

expression, and is critical in the development of the cerebellum as well as in

many other processes that are impaired in autism. Dr. Hu's earlier research

found that RORA was decreased in the autistic brain. In this study, the research

group demonstrates that aromatase, a protein which is regulated by RORA, is also

reduced in autistic brains.

This is significant because aromatase converts testosterone to estrogen. Thus, a

decrease in aromatase is expected to lead in part to build up of male hormones

which, in turn, further decrease RORA expression, as demonstrated in this study

using a neuronal cell model. On the other hand, female hormones were found to

increase RORA in the neuronal cells. The researchers believe that females may be

more protected against RORA deficiency not only because of the positive effect

of estrogen on RORA expression, but also because estrogen receptors, which

regulate some of the same genes as RORA, can help make up for the deficiency in

RORA.

" It is well known that males have a higher tendency for autism than females;

however, this new research may, for the first time, provide a molecular

explanation for why and how this happens. This is just the tip of the iceberg in

terms of understanding some of the biology underlying autism, and we will

continue our work to discover new ways to understand and, hopefully, to someday

combat this neurodevelopmental disorder, " said Dr. Hu.

In her research published in 2009, Dr. Hu and colleagues found that RORA

deficiencies were only apparent in the most severe cases of autism and were

observed in the brain tissues of both male and female subjects. They further

found that the deficiency in RORA was linked to a chemical modification of the

gene (called methylation) which effectively reduces the level of RORA.

Provided by Washington University Medical Center