Unique distribution of aromatase in the human brain: In vivo studies with PET and [N‐methyl‐11C]vorozole

Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Synapse (Impact Factor: 2.43). 11/2010; 64(11):801-7. DOI: 10.1002/syn.20791
Source: PubMed

ABSTRACT Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-(11)C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V(T)) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V(T) in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.

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Available from: Youwen Xu, Jul 29, 2015
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    • "Similar results have been observed for other models of learning and memory in mammals such as spatial learning (Frick, 2009; Packard and Teather, 1997) and discrimination learning in the auditory (Banerjee and Liu, 2013) and olfactory (Dillon et al., 2013) systems. If E2 has similar effects in the human brain, which is considered possible (Biegon et al., 2010; Roselli et al., 2009), then E2 deficits could contribute to deficits in verbal memory and communication. A better understanding of the role of steroid hormones in human learning and memory can contribute to the design of treatments for an aging population confronted with the onset of dementia, in post-menopausal women that suffer cognitive disorders thought to result from low E2 (Sherwin, 1998; Philips and Sherwin, 1992; Hogervorst et al., 1999), and for people taking aromatase inhibitors as treatment for estrogen-dependent cancers, such as breast cancer (Philips et al., 2011). "
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    • "In addition, in vitro studies report that hippocampal estradiol synthesis is important for the maintenance of hippocampal spines, synapses and synaptic proteins in cultures from rats (Hojo et al., 2004), and a recent in vivo study showed that hippocampal spine density correlated with hippocampal estradiol concentrations over the estrus cycle (Kato et al., 2013). Aromatase has been detected in human brain via immunocytochemistry, gene expression and in vivo PET scan studies (Biegon et al., 2010), but whether neurally derived estradiol plays a role in development or in neuromodulation is unexplored. An important question for the present review is whether neurally derived estrogens contribute to learning and memory. "
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