Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole.
Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole.
复制标题
DOI：
10.1002/syn.20791
复制
发表时间：
2010-11
期刊：
影响因子：
2.3
通讯作者：
Fowler, Joanna S.
中科院分区：
文献类型：
--
作者：
Biegon, Anat;Kim, Sung Won;Alexoff, David L.;Jayne, Millard;Carter, Pauline;Hubbard, Barbara;King, Payton;Logan, Jean;Muench, Lisa;Pareto, Deborah;Schlyer, David;Shea, Colleen;Telang, Frank;Wang, Gene-Jack;Xu, Youwen;Fowler, Joanna S.
芳香化酶催化雌激素生物合成的最后一步。脑芳香化酶参与多种神经生理和行为功能，包括性行为、攻击、认知和神经保护。使用正电子发射断层扫描（PET）与放射性标记的芳香化酶抑制剂[N-甲基-11 C]伏罗唑，我们的特点是示踪剂的分布和动力学在活的人脑。6名年轻健康受试者，3名男性和3名女性，在两个不同的场合单独给予放射性示踪剂。女性在月经周期的不同阶段接受扫描。通过预先给予药理学剂量（2.5 mg）的芳香酶抑制剂来曲唑确认特异性。在90分钟内采集PET数据，并将感兴趣区域放置在选定的脑区域上。脑和血浆时间活性曲线，校正代谢产物，用于推导动力学参数。男性和女性的分布容积（VT）值均遵循以下顺序：丘脑>杏仁核=视前区>延髓（下橄榄）>脑桥、枕叶和颞叶皮质、壳核、小脑和白色物质。来曲唑预处理可降低所有区域的VT，但降低的大小具有区域依赖性;范围从丘脑和视前区的~70%阻滞到小脑的~10%阻滞。丘脑和延髓（下橄榄）中芳香化酶的高水平似乎是人类所独有的。这些研究为非侵入性评估芳香酶参与影响人类大脑的各种生理和病理过程奠定了基础。
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-11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, 3 men and 3 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 (2.5mg) 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 (VT) values in both men and women followed the rank order: thalamus>amygdala=preoptic area>medulla(inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region dependent; ranging from ~70% blocking in thalamus and preoptic 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 non-invasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.
登录
查看更多内容
影响因子：
3.1
作者：
Lidstrom, P;Bonasera, TA;Langstrom, B
通讯作者：
Langstrom, B
影响因子：
3.1
作者：
ALEXOFF, DL;SHEA, C;WOLF, AP
通讯作者：
WOLF, AP
影响因子：
3.1
作者：
Logan, J
通讯作者：
Logan, J
影响因子：
4.8
作者：
ROSELLI, CE;ELLINWOOD, WE;RESKO, JA
通讯作者：
RESKO, JA
DOI：
10.1097/00004647-200106000-00002
发表时间：
2001-06-01
影响因子：
6.3
作者：
Gunn, RN;Gunn, SR;Cunningham, VJ
通讯作者：
Cunningham, VJ