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

本研究对下丘脑神经元控制促性腺激素和催乳素分泌的机制进行了研究。首先，研究了糖皮质激素在细胞因子抑制大鼠下丘脑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，而肾上腺切除可增强脉冲发生器的活性。皮质酮的注射恢复了在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，h型下丘脑-垂体-肾上腺轴的激活也支持下丘脑-垂体-性腺的功能。在山羊身上，研究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，雄性信息素增加了漏斗结节多巴胺能神经元的兴奋性，导致催乳素分泌减少。此外，作为大鼠下丘脑关键时期雌激素诱导基因，我们还鉴定了颗粒蛋白(GRN)基因。为阐明GIN在脑性分化中的作用，将GIN前体基因的反义寡核苷酸(ODN)注入2日龄雄性大鼠第三脑室。成熟期后，经GIN反义ODN处理的动物在评价性行为的各项参数上的得分均显著低于对照组，提示GIN基因在大鼠脑男性化过程中起着关键作用。

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.