PET Scans Reveal Estrogen-Producing Hotspots in Human Brain

Researchers at a U.S. National lab have demonstrated that a molecule "tagged” with a radioactive form of carbon can be used to image aromatase, an enzyme responsible for the production of estrogen, in the human brain. Moreover, the research revealed that the areas of the brain where aromatase is concentrated might be unique to humans.

"The original purpose of the study was to expand our use of this radiotracer, N-methyl-¹¹C vorozole,” said Dr. Anat Biegon, a neurobiologist at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory (Upton, NY, USA). "Proving that a radiotracer like vorozole can be used for brain-imaging studies in humans would be a gateway to new research on estrogen in the brain. You cannot look at these brain pathways in living humans in any other way.”

Vorozole binds to aromatase, a vital catalyst in the biosynthesis of estrogen. Since estrogen is implicated in a range of conditions and pathologies, from breast cancer to Alzheimer's disease, studying its production in the human body using noninvasive imaging techniques such as positron emission tomography (PET) imaging can be a useful diagnostic and investigative tool. This is the first study to demonstrate that vorozole is a useful radiotracer for studying estrogen-producing hotspots in the human brain.

The investigators employed PET imaging to scan the brains of six young, healthy nonsmoking subjects--three men and three women. Researchers scanned the female subjects at either the midcycle or the early follicular phase of the menstrual cycle, to incorporate variation in plasma estrogen levels. Before scanning, all subjects received an injection containing a radiolabeled form of vorozole, synthesized and purified by radiochemists at Brookhaven. The men underwent a second scan after being administered an aromatase inhibitor. As expected, subjects who received the inhibitor demonstrated low concentrations of radioactive vorozole, indicating lower availability of aromatase, compared to those not exposed to the inhibitor.

The scientists found a shocker, however, in the "geographic” (anatomic) distribution of aromatase in the brain. The highest levels of aromatase appeared in the thalamus and then the medulla, in a pattern that was consistent across all six subjects. This differs from what researchers have observed previously in animal studies, where aromatase is concentrated in smaller regions, principally the amygdala and preoptic areas. "This started as a simple tool development study and now it's turned out to be much more interesting than that,” Dr. Biegon noted. "The question that's raised is what is aromatase doing in these particular brain regions?”

To answer this, Dr. Biegon and her colleagues have already started evaluating a larger group of 30 subjects. They will examine differences in brain aromatase related to a range of factors including age, sex, personality, and memory. Beginning with healthy subjects and advancing to patients with specific conditions and diseases, they plan to examine the role of estrogen in the brain in relation to disorders and diseases such as unusual aggression, breast cancer, and Alzheimer's disease.

The research was published in the November 2010 issue of the journal Synapse.

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Brookhaven National Laboratory