Rapid control of brain aromatase activity by glutamatergic inputs
Rapid control of brain aromatase activity by glutamatergic inputs
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DOI：
10.1210/en.2005-0845
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Ball, GF
中科院分区：
文献类型：
--
作者：
Balthazart, J;Baillien, M;Ball, GF
来自睾酮的神经芳构化的雌激素在许多脊椎动物的雄性性行为的激活中起关键作用，并且现在已被认识到对脑功能具有快速的膜效应。芳香化酶活性的这种变化以及由此引起的局部雌激素浓度的变化可以迅速调节行为反应。我们在这里表明，有一个非常快速的（在几分钟内）减少芳香酶活性鹌鹑下丘脑外植体暴露于影响细胞内Ca 2+浓度的治疗，如添加谷氨酸激动剂（红藻氨酸，α-氨基-3-羟甲基-4-异恶唑丙酸，并在较小程度上，N-甲基-D-天冬氨酸），但不是γ-氨基丁酸。在5分钟内观察到红藻氨酸盐作用，其使芳香酶活性降低25- 50%，在暴露于特定红藻氨酸盐拮抗剂（6-氰基-7-硝基喹喔啉-2，3-二酮二钠或1，2，3，4-四氢-6-硝基-2，3-二氧代-苯并[f]喹喔啉-7-磺酰胺二钠）的外植体中完全阻断，并且当效应物被洗掉时也是快速可逆的。总之，这些数据支持这样的观点，即雌激素的合成可以在大脑中快速调节，从而产生局部雌激素生物利用度的快速变化，这可以快速改变大脑功能，其时间过程类似于先前描述的神经递质和神经调质。
Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on brain function. Such changes in aromatase activity and hence in local estrogen concentrations could rapidly modulate behavioral responses. We show here that there is a very rapid (within minutes) decrease in aromatase activity in quail hypothalamic explants exposed to treatments affecting intracellular Ca2+ concentrations, such as the addition of glutamate agonists (kainate, alpha-amino-3-hydroxymethyl-4-isoxazole propionic acid, and, to a much lesser extent, N-methyl-D-aspartate), but not of gamma-aminobutyric acid. The kainate effects, which reduce aromatase activity by 25-50%, are observed within 5 min, are completely blocked in explants exposed to specific kainate antagonists (6-cyano-7-nitroquinoxaline-2,3-dione disodium or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and are also rapidly reversible when effectors are washed out. Together, these data support the idea that the synthesis of estrogen can be rapidly regulated in the brain, thus producing rapid changes in local estrogen bioavailability that could rapidly modify brain function with a time course similar to what has previously been described for neurotransmitters and neuromodulators.