Mitsushima Dai, Takase Kenkichi, Funabashi Toshiya, Kimura Fukuko
Department of Physiology, Yokohama City University Graduate School of Medicine, 236-0004 Yokohama, Japan.
J Neurosci. 2009 Mar 25;29(12):3808-15. doi: 10.1523/JNEUROSCI.5301-08.2009.
Extracellular acetylcholine (ACh) levels in the dorsal hippocampus increases during learning or exploration, exhibiting a sex-specific 24 h release profile. To examine the activational effect of gonadal steroid hormones on the sex-specific ACh levels and its correlation with spontaneous locomotor activity, we observed these parameters simultaneously for 24 h. Gonadectomy severely attenuated the ACh levels, whereas the testosterone replacement in gonadectomized males or 17beta-estradiol replacement in gonadectomized females successfully restored the levels. 17beta-Estradiol-priming in gonadectomized males could not restore the ACh levels, and testosterone replacement in gonadectomized females failed to raise ACh levels to those seen in testosterone-primed gonadectomized males, revealing a sex-specific activational effect. Spontaneous locomotor activity was not changed in males by gonadectomy or the replacement of gonadal steroids, but 17beta-estradiol enhanced the activity in gonadectomized females. Gonadectomy severely reduced the correlation between ACh release and activity levels, but the testosterone replacement in gonadectomized males or 17beta-estradiol replacement in gonadectomized females successfully restored it. To further analyze the sex-specific effect of gonadal steroids, we examined the organizational effect of gonadal steroids on the ACh release in female rats. Neonatal testosterone or 17beta-estradiol treatment not only increased the ACh levels but also altered them to resemble male-specific ACh release properties without affecting levels of spontaneous locomotor activity. We conclude that the activational effects of gonadal steroids maintaining the ACh levels and the high correlation with spontaneous locomotor activity are sex-specific, and that the organizational effects of gonadal steroids suggest estrogen receptor-mediated masculinization of the septo-hippocampal cholinergic system.
在学习或探索过程中，背侧海马体中的细胞外乙酰胆碱（ACh）水平会升高，呈现出性别特异性的24小时释放模式。为了研究性腺类固醇激素对性别特异性ACh水平的激活作用及其与自发运动活动的相关性，我们同时观察了这些参数24小时。去势严重减弱了ACh水平，而在去势雄性大鼠中补充睾酮或在去势雌性大鼠中补充17β-雌二醇成功恢复了该水平。在去势雄性大鼠中用17β-雌二醇预处理不能恢复ACh水平，在去势雌性大鼠中补充睾酮也未能将ACh水平提高到用睾酮预处理的去势雄性大鼠的水平，这揭示了性别特异性的激活作用。去势对雄性大鼠的自发运动活动没有影响，补充性腺类固醇也未改变其自发运动活动，但17β-雌二醇增强了去势雌性大鼠的自发运动活动。去势严重降低了ACh释放与活动水平之间的相关性，但在去势雄性大鼠中补充睾酮或在去势雌性大鼠中补充17β-雌二醇成功恢复了这种相关性。为了进一步分析性腺类固醇的性别特异性作用，我们研究了性腺类固醇对雌性大鼠ACh释放的组织化作用。新生大鼠接受睾酮或17β-雌二醇处理不仅增加了ACh水平，还使其类似于雄性特异性的ACh释放特性，而不影响自发运动活动水平。我们得出结论，性腺类固醇维持ACh水平以及与自发运动活动高度相关的激活作用具有性别特异性，并且性腺类固醇的组织化作用表明雌激素受体介导了隔区-海马胆碱能系统的雄性化。
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