Montague D, Weickert C S, Tomaskovic-Crook E, Rothmond D A, Kleinman J E, Rubinow D R
Behavioural Endocrinology Branch, National Institute of Mental Health, Bethesda, MD, USA.
J Neuroendocrinol. 2008 Jul;20(7):893-903. doi: 10.1111/j.1365-2826.2008.01743.x. Epub 2008 Apr 28.
Oestrogen modulates cognitive function and affective behaviours subserved by the prefrontal cortex (PFC). Identifying and localising oestrogen receptor (ER)alpha, in human PFC will contribute to our understanding of the molecular mechanism of oestrogen action in this region. Inferences about the site of action of oestrogen in human brain are derived largely from studies performed in nonhuman mammalian species; however, the congruence of findings across species has not been demonstrated. Furthermore, the laminar, cellular, and subcellular localisation of ERalpha in the cortex is debated. Therefore, we compared the distribution of ERalpha in human dorsolateral prefrontal cortex (DLPFC) with that of monkey DLPFC and rat medial PFC. Immunohistochemistry performed on frontal cortex from the three species demonstrated ERalpha positive cells throughout all layers of the PFC, in pyramidal and nonpyramidal neurones, with both nuclear and cytoplasmic immunoreactivity. Western blot analyses and preabsorption studies confirmed that the antibody used recognised ERalpha and not ERbeta. A strong ERalpha immunoreactive band corresponding to the full-length ERalpha protein (65-67 kDa) in the frontal cortex of all three species matched the size of the predominant immunoreactive band detected in breast cancer cell lines known to express ERalpha. Additionally, other ERalpha immunoreactive proteins of varying molecular weight in breast cancer cells, rat ovary and mammalian brain were detected, suggesting that ERalpha may exist in more than one form in the mammalian frontal cortex. The present study provides evidence that ERalpha protein exists in neurones in mammalian PFC and that ERalpha is anatomically well-positioned to directly mediate oestrogen action in these neurones.
雌激素调节前额叶皮质（PFC）所维持的认知功能和情感行为。在人类PFC中鉴定和定位雌激素受体（ER）α，将有助于我们理解雌激素在该区域作用的分子机制。关于雌激素在人类大脑中作用位点的推断，很大程度上来自于在非人类哺乳动物物种中进行的研究；然而，尚未证实跨物种研究结果的一致性。此外，ERα在皮质中的层状、细胞和亚细胞定位也存在争议。因此，我们比较了人类背外侧前额叶皮质（DLPFC）、猴DLPFC和大鼠内侧PFC中ERα的分布。对这三个物种的额叶皮质进行免疫组织化学分析，结果显示在PFC的所有层中，锥体细胞和非锥体细胞的ERα阳性细胞均具有核和细胞质免疫反应性。蛋白质印迹分析和预吸收研究证实，所用抗体识别的是ERα而非ERβ。在所有三个物种的额叶皮质中，与全长ERα蛋白（65 - 67 kDa）相对应的强ERα免疫反应条带，与已知表达ERα的乳腺癌细胞系中检测到的主要免疫反应条带大小一致。此外，还检测到乳腺癌细胞、大鼠卵巢和哺乳动物大脑中分子量不同的其他ERα免疫反应蛋白，这表明ERα在哺乳动物额叶皮质中可能以多种形式存在。本研究提供了证据，证明ERα蛋白存在于哺乳动物PFC的神经元中，并且在解剖学上处于良好位置，可直接介导这些神经元中的雌激素作用。
