Alteration in [11C]vorozole binding to aromatase in neuronal cells of rat brain induced by anabolic androgenic steroids and flutamide.
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.
Takahashi
Kayo
K
Molecular Probe Dynamics Laboratory, Molecular Imaging Research Program, RIKEN, Kobe, Japan. kayo.takahashi@riken.jp
Tamura
Yasuhisa
Y
Watanabe
Yasuyoshi
Y
Långström
Bengt
B
Bergström
Mats
M
D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000201:enzymology; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D005485:Flutamide / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D049268:Positron-Emission Tomography; D011301:Preoptic Area / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D012686:Septal Nuclei / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology; D014230:Triazoles / Q000378:metabolism / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000726:Androgen Antagonists; D000728:Androgens; D047072:Aromatase Inhibitors; D002250:Carbon Radioisotopes; D011944:Receptors, Androgen; D014230:Triazoles; C060523:vorozole; D005485:Flutamide; D001141:Aromatase