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Alteration in [11C]vorozole binding to aromatase in neuronal cells of rat brain induced by anabolic androgenic steroids and flutamide
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2008 (English)In: NeuroReport, ISSN 0959-4965, Vol. 19, no 4, 431-435 p.Article in journal (Refereed) Published
Abstract [en]

In a previous study, we demonstrated that androgenic-anabolic steroids increased aromatase expression in the bed nucleus of stria terminalis and preoptic area in rat brain, as evaluated using autoradiography with [11C]vorozole, a potential positron emission tomography tracer for aromatase. In this study, we explored whether the increase in aromatase binding is mediated via androgen receptors and whether this increase occurs in neurons or glial cells. Rats were given nandrolone decanoate (15 mg/kg body weight once every 3 days) and flutamide (20 mg/kg/day) alone or in combination for 20 days. Results indicated a significant increase of [11C]vorozole binding by nandrolone decanoate in the bed nucleus of the stria terminalis and preoptic area, as in our previous study. Flutamide treatment, on the other hand, decreased [11C]vorozole binding in the bed nucleus of the stria terminalis, preoptic area, and medial amygdala. Immunohistochemical examination demonstrated that upregulation of aromatase expression occurred in neurons. Our findings suggest that aromatase is regulated through an androgen receptor-mediated system. This aromatase-specific tracer and the positron emission tomography technique could be useful for exploring the role of aromatase in anabolic androgenic steroids abusers.

Place, publisher, year, edition, pages
2008. Vol. 19, no 4, 431-435 p.
Keyword [en]
amygdala, anabolic steroids, aromatase, bed nucleus of the stria terminalis, [11C]vorozole, positron emission tomography, preoptic area
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-97477DOI: 10.1097/WNR.0b013e3282f7cdb7ISI: 000253884900008PubMedID: 18287941OAI: oai:DiVA.org:uu-97477DiVA: diva2:172444
Available from: 2008-09-08 Created: 2008-09-08 Last updated: 2009-11-16Bibliographically approved
In thesis
1. Imaging brain aromatase by using PET: A way to study anabolic steroid abuse
Open this publication in new window or tab >>Imaging brain aromatase by using PET: A way to study anabolic steroid abuse
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aromatase is an enzyme that facilitates the conversion of androgens to estrogens and may play a role in mood and mental status. The main theme of this thesis is the imaging of brain aromatase by use of the PET technique. The PET tracer for aromatase, 11C-labeled vorozole (VOZ) was developed and evaluated by with in vitro and in vivo methods. In vitro experiments using rat brain showed that VOZ was distributed in the medial amygdala, bed nucleus of the stria terminalis and medial preoptic area, regions of the brain known to be rich in aromatase and the KD value was determined to be 0.60 nM. The in vivo PET study in rhesus monkey brain revealed that VOZ penetrated the blood-brain barrier and accumulated in the amygdala and hypothalamus. Taken together, VOZ is a good PET tracer for in vivo aromatase imaging with high affinity and high sensitivity.

This technique was applied to an investigation of brain aromatase under the physiological conditions simulating anabolic-androgenic steroid abuse. A significant increase in VOZ binding by anabolic-androgenic steroids was observed in the bed nucleus of stria terminalis and medial preoptic area in the rat brain. In contrast, no significant change in binding was observed in the medial amygdala. These results indicate that the manner of regulation of aromatase expression might be different in the bed nucleus of stria terminalis and medial preoptic area compared with that in the medial amygdala. The aromatase expression was suggested to be regulated through androgen receptors, as indicated in a study with flutamide treatment. The increased aromatase expression was seen in neurons. The PET study with anabolic steroid-treated rhesus monkeys also showed increased VOZ binding in the hypothalamus but not in the amygdala. The alteration of density of aromatase binding in the hypothalamic area could explain some psychological features of anabolic-androgenic steroid abusers.

Novel PET tracers for aromatase were developed and examined. The two newly synthesized 18F-labeled vorozole analogs, [18F]FVOZ and [18F]FVOO, displayed different characteristics. Both tracers showed similar binding pattern as VOZ; however, [18F]FVOO was metabolized very quickly, meaning that this tracer is not suitable as a PET tracer. On the other hand, [18F]FVOZ can be an appropriate PET tracer.

The role of aromatase in the human brain has not been clarified yet. To approach this problem by in vivo methods, we have just started PET studies to explore aromatase expression in humans.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 63 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 370
aromatase, brain, molecular imaging, PET, [11C]Vorozole, amygdala, hypothalamus, anabolic-androgenic steroids, abuse, [18F]Vorozole analogs
National Category
urn:nbn:se:uu:diva-9234 (URN)978-91-554-7266-5 (ISBN)
Public defence
2008-10-04, B42, A4, BMC, Uppsala, 09:15
Available from: 2008-09-08 Created: 2008-09-08Bibliographically approved

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