Decreased brain aromatase availability in overweight humans

340 Objectives Aromatase, the Cyp19A gene product, is the last enzyme in estrogen biosynthesis from androgens. The aromatase gene is locally expressed and differentially regulated in many organs and tissues (i.e. fat cells, brain). Aromatase expression is reportedly increased in fat tissue of subjects with a high body mass index (BMI), but the relationship between BMI and brain aromatase availability has not been investigated. Here we use [C-11]vorozole, an aromatase inhibitor tracer to assess aromatase availability in brain of overweight humans with PET. Methods Five healthy overweight subjects (3F/2M, 39.3±14.8 y/o, BMI = 29±2.8) and 13 age matched normal weight subjects (5F/8M, 35.1±15.5 y/o, BMI = 22.8±1.7) were scanned with [C-11]vorozole. PET data were acquired over a 90 min session and regions of interest placed bilaterally over selected brain regions (hypothalamus, amygdala, thalamus and cortical white matter). Brain and plasma time activity data were used to calculate the total distribution volume (VT) from a two-compartment model. The results were analyzed by 2-way ANOVA with repeated measures (group x region) and Pearson’s regression analysis. Results High BMI was associated with a significant (p Conclusions Reduced availability of aromatase in the brain of overweight subjects implies reduced conversion of androgens to estrogens in the brain. This finding is in line with animal data showing decreased food intake in animals administered with estradiol in the hypothalamus and other nuclei and supports the notion that human aromatase expression is regulated in a tissue-specific manner. Research Support Supported by DOE/OBER-infrastructure and BNL