Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory
Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory
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DOI：
10.1016/s0166-4328(99)00082-0
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发表时间：
1999-11-01
影响因子：
2.7
通讯作者：
McQueen, J
中科院分区：
文献类型：
--
作者：
Fink, G;Sumner, B;McQueen, J
性类固醇对人的情绪和精神状态有强有力的影响。我们之前在雌性大鼠身上的实验结果表明，这些作用可能部分是由雌激素对5-羟色胺的作用介导的（2A）。受体（5-HT(2A)R）和血清素转运体（SERT）。在这里，我们回顾了我们最近关于急性（类似于32小时）睾酮操纵对雄性大鼠中枢5-羟色胺（2A）R和SERT的影响的研究结果。去势降低了睾酮和雌激素水平，但不影响5 α -二氢睾酮（5 α - dht）的作用，显著增加了中脑背核（DR）中5- ht (2A)R mRNA和SERT mRNA的含量以及大脑高级中枢5- ht (2A)R和SERT结合位点的密度。5 -二氢睾酮（一种不能转化为雌激素的强效雄激素）缺乏作用，表明睾酮的作用取决于其通过芳香化酶转化为雌激素。这也可以解释为什么雌激素，而不是睾酮或5- dht，增加了尾状壳核中5-羟色胺（2A）R结合位点的密度，尾状壳核是芳香化酶稀缺的大脑区域。雌激素对SERT mRNA的诱导在吻侧DR中最为突出，这与DR血清素神经元对雌激素和神经毒性安非他明衍生物的敏感性之间的相关性一起，为研究睾酮/雌激素对SERT基因表达的调节提供了一个潜在的拓扑化学处理方法。这些发现讨论了性类固醇和血清素机制在情绪障碍、精神分裂症和阿尔茨海默病中的相互作用的可能作用。(C) 1999 Elsevier Science B.V.版权所有
Sex steroids exert potent effects on mood and mental state in the human. Our previous experimental findings in female rats suggest that these effects may be mediated, in part, by the action of estrogen on the 5-hydroxytryptamine(2A). receptor (5-HT(2A)R) and serotonin transporter (SERT) in brain. Here we review our recent findings on the effect of acute (similar to 32 h) testosterone manipulation on central 5-HT(2A)R and SERT in male rats. Castration decreased while testosterone or estrogen, but not 5 alpha-dihydrotestosterone (5 alpha-DHT), increased significantly the content of 5-HT(2A)R mRNA and SERT mRNA in the dorsal raphe nucleus (DR) and the density of 5-HT(2A)R and SERT binding sites in higher centers of the brain. The lack of effect of 5 alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5 alpha-DHT, increased the density of 5-HT(2A)R binding sites in the caudate-putamen, a brain region where aromatase is scarce. The estrogen induction of SERT mRNA is most prominent in the rostral DR and this together with the correlation between sensitivity of DR serotonin neurons to estrogen and neurotoxic amphetamine derivatives provides a potential topochemical handle with which to investigate testosterone/estrogen regulation of SERT gene expression. These findings are discussed in relation to the possible role of interactions between sex steroids and serotonin mechanisms in mood disorders, schizophrenia and Alzheimer's disease. (C) 1999 Elsevier Science B.V. All rights reserved.