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

在本研究中，下丘脑神经元控制的促性腺激素和催乳素分泌的机制进行了研究。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。肿瘤坏死因子抑制脉冲发生器的活动，增强肾上腺切除术。注射皮质酮恢复了肾上腺切除动物中观察到的过度抑制，这表明即使在应激条件下，下丘脑-垂体-肾上腺轴的激活也支持下丘脑-垂体-性腺功能。在山羊中，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，结节漏斗多巴胺能神经元的兴奋性被发现增加男性信息素，从而减少催乳素分泌。此外，我们还鉴定了关键期大鼠下丘脑中的一个雌激素诱导基因--颗粒蛋白（grn）基因。为了阐明gin在脑性分化中的作用，将gin前体基因的反义寡聚脱氧核苷酸（ODN）注入2日龄雄性大鼠的第三脑室内。成熟后，与对照组相比，用反义寡核苷酸处理的动物在评估性行为的各种参数上的得分显著降低，表明gin基因在大鼠脑的雄性化过程中起着至关重要的作用。

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.