Abstract
The enzyme aromatase catalyzes the final step in estrogen biosynthesis, converting testosterone to estradiol, and is expressed in the brain of all mammals. Estrogens are thought to be important for maintenance of cognitive function in women, whereas testosterone is thought to modulate cognitive abilities in men. Here, we compare differences in cognitive performance in relation to brain aromatase availability in healthy men and women. Twenty-seven healthy participants were administered tests of verbal learning and memory and perceptual/abstract reasoning. In vivo images of brain aromatase availability were acquired in this sample using positron emission tomography (PET) with the validated aromatase radiotracer [11C]vorozole. Regions of interest were placed bilaterally on the amygdala and thalamus where aromatase availability is highest in the human brain. Though cognitive performance and aromatase availability did not differ as a function of sex, higher availability of aromatase in the amygdala was associated with lower cognitive performance in men. No such relationship was found in women; and the corresponding regression slopes were significantly different between the sexes. Thalamic aromatase availability was not significantly correlated with cognitive performance in either sex. These findings suggest that the effects of brain aromatase on cognitive performance are both region- and sex-specific and may explain some of the normal variance seen in verbal and nonverbal cognitive abilities in men and women as well as sex differences in the trajectory of cognitive decline associated with Alzheimer’s disease.
Highlights
The last and obligatory step in estrogen biosynthesis in all organs and species is catalyzed by the enzyme aromatase, which converts the androgens androstenedione and testosterone, to the estrogens, estrone, and estradiol (Simpson et al, 2002)
There were no significant differences between men and women in age, education estimates, and aromatase availability in the amygdala and thalamus (Table 1)
Amygdala aromatase availability correlated with cognitive performance scores (Table 3)
Summary
The last and obligatory step in estrogen biosynthesis in all organs and species is catalyzed by the enzyme aromatase (estrogen synthase, Cyp gene product), which converts the androgens androstenedione and testosterone, to the estrogens, estrone, and estradiol (Simpson et al, 2002). The ovary is the primary source of circulating estrogens (Simpson, 2003). In both sexes, a major site of extra-gonadal estrogen synthesis is the brain, and it. A recent study revealed some regionand sex-specific associations between aromatase availability in the human brain and personality characteristics (Takahashi et al, 2018). Further support of the role of aromatase in human cognition comes from postmortem studies in humans, which demonstrate region-specific changes in aromatase levels in Alzheimer’s disease (Ishunina et al, 2005; Prange-Kiel et al, 2016), suggesting that aromatase may be implicated in normal as well as pathological variations in learning and memory
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