Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke.
Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke.
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DOI：
10.1186/s13293-020-00357-w
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发表时间：
2021-01-07
影响因子：
7.9
通讯作者：
McCullough LD
中科院分区：
文献类型：
--
作者：
Manwani B;Fall P;Zhu L;O'Reilly MR;Conway S;Staff I;McCullough LD
中风的性别差异归因于雌激素的神经保护作用，但大多数补充雌激素预防中风的临床试验都失败了。性激素对中风预后的影响仍是一个有争议的话题。神经组织中睾酮芳构化为雌二醇导致性别分化。新出现的数据表明芳香化酶活性在脑损伤中增加，并且在动物模型的缺血半暗带中观察到芳香化酶表达增加。本研究的目的是检测急性缺血性卒中后内源性类固醇的水平，并确定性类固醇水平是否与急性卒中结局相关。在症状发作后24小时内，根据经批准的IRB采集缺血性卒中患者和对照组的外周血。使用ELISA测量男性和女性血清中的17β-雌二醇、睾酮和芳香化酶水平。比较了卒中组和对照组中男性与女性的激素水平，并使用多变量回归将其与结局（NIHSS和改良兰金量表（mRS）的变化（定义为发病前和出院时mRS的差异）相关。我们发现男性（p = 0.86）或女性（p = 0.10）卒中后24小时雌二醇水平无显著差异。在男性中，与对照组相比，中风后睾酮显著降低（1.83 ± 0.12 vs. 2.86 ± 0.65，p = 0.01）。与对照组相比，中风后女性的芳香化酶水平显著升高（2.27 ± 0.22 vs. 0.97 ± 0.22，p = 0.002），但男性中没有（p = 0.84）。在女性（r = 0.38，p = 0.02）和男性（r = 0.3，p = 0.04）中，雌二醇水平与mRS变化呈正相关。在男性和女性中，至少在卒中急性期（24小时），ESTA水平与功能结局（mRS变化）相关。然而，男性或女性中风后24小时雌二醇水平无显著差异。男性中风后24小时睾酮水平下降。正如在动物模型中所看到的，急性缺血性中风后芳香化酶水平增加，但这仅适用于女性。这表明急性缺血性卒中后绝经后妇女的主动芳构化过程。
Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes. Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 h of symptom onset. 17β-estradiol, testosterone, and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as the difference of premorbid and discharge mRS) using multivariate regression. We found no significant difference in estradiol levels 24 h after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs. 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27 ± 0.22 vs. 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with change in mRS in both women (r = 0.38, p = 0.02) and men (r = 0.3, p = 0.04). Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 h) of stroke. However, no significant difference in estradiol levels is seen 24 h post-stroke in men or women. Testosterone levels decrease at 24 h after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
6.3
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