Pronina T, Ugrumov M, Calas A, Seif I, Tramu G
Laboratory of Hormonal Regulations, Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
J Neuroendocrinol. 2003 Oct;15(10):925-32. doi: 10.1046/j.1365-2826.2003.01072.x.
This study evaluated the influence of monoamines, serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline, on differentiating gonadotropin-releasing hormone (GnRH)-producing neurones in foetal mice. The differentiation and migration of GnRH neurones were compared in Tg8 mice (the knocked-out gene encoding monoamine oxidase A) with increased levels of 5-HT and noradrenaline and in C3H mice with normal metabolism of monoamines in C3H mice. To achieve this, immunocytochemistry for GnRH combined with quantitative and semiquantitative image analysis were employed. GnRH neurones in foetuses at the 18th embryonic day were detected in the forebrain along the trajectory of their migration from the olfactory bulbs to the hypothalamic retrochiasmatic region. The total number of GnRH neurones in the forebrain in knockout mice was significantly lower compared to C3H mice, suggesting an inhibiting influence of monoamines on the proliferation of precursor cells. The fraction of GnRH neurones in the caudal part of the trajectory of their migration in Tg8 mice exceeded significantly those in C3H foetuses, whereas there was a reverse in the rostral part of the trajectory. These data suggest that an excess of 5-HT and noradrenaline served to accelerate the GnRH neurone migration in Tg8 mice. Moreover, an excess of 5-HT and noradrenaline provided a minor effect on the area and optical density of GnRH neurones (i.e. on GnRH neurone differentiation). Thus, an excess of 5-HT and noradrenaline appears to inhibit the proliferation of the precursor cells of GnRH neurones and stimulates the GnRH neurone migration to the place of their final location in the septo-preoptic region.
本研究评估了单胺类物质、血清素（5-羟色胺，5-HT）和去甲肾上腺素对胎鼠中促性腺激素释放激素（GnRH）生成神经元分化的影响。比较了5-HT和去甲肾上腺素水平升高的Tg8小鼠（编码单胺氧化酶A的基因敲除小鼠）与单胺代谢正常的C3H小鼠中GnRH神经元的分化和迁移情况。为此，采用了GnRH免疫细胞化学结合定量和半定量图像分析的方法。在胚胎第18天的胎鼠前脑中，沿着从嗅球到下丘脑视交叉后区域的迁移轨迹检测到了GnRH神经元。与C3H小鼠相比，基因敲除小鼠前脑中GnRH神经元的总数显著减少，这表明单胺类物质对前体细胞的增殖有抑制作用。在Tg8小鼠中，GnRH神经元迁移轨迹尾部的GnRH神经元比例显著超过C3H胎鼠，而在迁移轨迹头部则相反。这些数据表明，5-HT和去甲肾上腺素过量有助于加速Tg8小鼠中GnRH神经元的迁移。此外，5-HT和去甲肾上腺素过量对GnRH神经元的面积和光密度（即对GnRH神经元分化）有轻微影响。因此，5-HT和去甲肾上腺素过量似乎抑制了GnRH神经元前体细胞的增殖，并刺激GnRH神经元迁移到它们在隔区-视前区最终定位的位置。
