Study: PET + vorozole reveal estrogen production in human brain

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PET with the radiolabeled N-methyl-11C vorozole can be used to image aromatase, an enzyme responsible for the production of estrogen in the human brain, according to research published in the November issue of Synapse.

N-methyl-11C vorozole binds to aromatase, which catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition and neuroprotection.

"The original purpose of the study was to expand our use of this radiotracer, N-methyl-11C vorozole," said Anat Biegon, PhD, senior scientist at Brookhaven National Laboratory in Upton, N.Y. "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."

The team used PET 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 early follicular phase of the menstrual cycle, to incorporate variation in plasma estrogen levels. Prior to the scans, all subjects received an injection containing a radiolabeled form of vorozole. The men underwent a second scan after being administered an aromatase inhibitor.

Subjects who received the aromatase inhibitor letrozole showed low concentrations of radioactive vorozole, indicating lower availability of aromatase, compared to those not exposed to the inhibitor, according to Biegon and colleagues.

The scientists found a surprise, however, in the anatomical 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 result differed from what researchers have observed previously in animal studies, where aromatase was concentrated in smaller regions, principally the amygdala and preoptic areas.

Biegon and her colleagues have already begun studying 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 intend to study the role of estrogen in the brain with respect to disorders and diseases such as unusual aggression, breast cancer and Alzheimer's disease.