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Analysis of hypothalamic neuronal system controlling the secretion of gonadotropin and prolactin

下丘脑控制促性腺激素和催乳素分泌的神经系统分析

基本信息

批准号：
08456148
负责人：
NISHIHARA Masugi
金额：
$ 4.8万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08456148/
关键词：
Gonadotropin Prolactin Hypothalamus Estrogen GnRH pulse generator Rat Mouse Goat

项目摘要

In the present study, hypothalamic neuronal mechanisms controlling the secretion of gonadotropin and prolactin were investigated. First, the role of glucocorticoid in the suppression of hypothalamic GnRH pulse generator activity by cytokines was studied in the rat. TNF suppressed pulse generator activity, which was enhanced by adrenalectomy. Injection of corticosterone restored excessive suppression observed in the adrenalectomized animals, suggesting that activation of h hypothalamo-pitui tary-adrenal axis supports hypothalamo-pituitary-gonadal function even under stress conditions. In the goat, it was found that male pheromones increased the electrical activity of the hypothalamic GnRH pulse generator. In the mouse, the excitability of tuberoinfundibular dopaminergic neurons were found to be increased by male pheromones with a resultant decrease in prolactin secretion. In addition, as a estrogen inducible gene in rat hypothalamus during the critical period, we identified the gene of granulin (grn). To elucidate the involvement of gin in sexual differentiation of the brain, the antisense oligodeoxynucleotide (ODN) of gin precursor gene was i*sed into the third ventricle of male rats at 2 day-old. After maturation, animals treated with antisense ODN of gin displayed significantly lower scores than control males on various parameters assessing sexual behavior, suggesting that gin gene plays a crucial role in the process of masculinization of rat brain.

在本研究中，研究了控制促性腺激素和催乳素分泌的下丘脑神经元机制。首先，在大鼠中研究了糖皮质激素在细胞因子抑制下丘脑 GnRH 脉冲发生器活性中的作用。 TNF 抑制脉冲发生器的活性，而肾上腺切除术则增强了脉冲发生器的活性。注射皮质酮恢复了在肾上腺切除动物中观察到的过度抑制，这表明下丘脑-垂体-肾上腺轴的激活即使在应激条件下也支持下丘脑-垂体-性腺功能。在山羊身上，发现雄性信息素增加了下丘脑 GnRH 脉冲发生器的电活动。在小鼠中，发现雄性信息素会增加结节漏斗部多巴胺能神经元的兴奋性，从而导致催乳素分泌减少。此外，我们还鉴定出了颗粒蛋白（grn）基因，作为大鼠下丘脑关键期雌激素诱导基因。为了阐明杜松子酒在大脑性别分化中的作用，将杜松子酒前体基因的反义寡脱氧核苷酸（ODN）注射到2日龄雄性大鼠的第三脑室中。成熟后，用杜松子酒反义ODN处理的动物在评估性行为的各种参数上表现出明显低于对照雄性的分数，表明杜松子酒基因在大鼠大脑男性化过程中发挥着至关重要的作用。