Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats
Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats
复制标题
DOI：
10.1262/jrd.18146
复制
发表时间：
2007-04-01
影响因子：
1.8
通讯作者：
Maeda, Kei-Ichiro
中科院分区：
文献类型：
--
作者：
Adachi, Sachika;Yamada, Shunji;Maeda, Kei-Ichiro
KiSS-1基因产物Metastin/Kisspeptin被认为是GPR54的内源性配体，据报道可以调节雌性大鼠的GnRH/LH峰和动情周期。本研究的目的是确定Metastin/Kisspeptin神经元是否是雌激素正反馈诱导GnRH/LH激增的靶点。我们证明，在视前区(POA)注入抗大鼠Metastin/Kisspeptin单抗可阻断雌激素诱导的LH峰，提示POA周围释放的内源性Metastin/Kisspeptin介导了雌激素对GnRH/Lh释放的正反馈效应。在高雌二醇(E-2)处理的雌性大鼠前腹侧脑室周围核(AVPV)中，c-Fos表达KiSS-1mRNA阳性细胞占KiSS-1mRNA阳性细胞的百分比在下午显著高于上午，因此，AVPV中的Metastin/Kisspeptin神经元可能参与了反馈效应。上午和下午弓状核(ARC)中c-Fos表达的Metastin/Kispeptin神经元的百分比没有差异。在AVPV和ARC中，KiSS-1mRNA表达的细胞大多含有ERα免疫反应性。此外，在雌性去卵巢动物中，AVPV KiSS-1mRNA的表达在动情前期下午最高，在动情间期最低，并且在去卵巢的动物中被雌激素处理后表达增加。而ARC KISS-1mRNA的表达在动情间期第2天最高，在动情前期下午最低，去卵巢后表达增加，高雌激素处理后表达降低。与高E-2处理的雌性相比，缺乏GnRH/LH释放峰模式的雄性在AVPV内没有明显的Metastin/Kisspeptin免疫反应神经元簇，后者显示这些神经元的密度要高得多。综上所述，本研究表明，AVPV metastin/kispeptin神经元是雌激素正反馈诱导雌性大鼠GnRH/LH峰升高的靶点。
Metastin/kisspeptin, the KiSS-1 gene product, has been identified as an endogenous ligand of GPR54 that reportedly regulates GnRH/LH surges and estrous cyclicity in female rats. The aim of the present study was to determine if metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges. We demonstrated that preoptic area (POA) infusion of the anti-rat metastin/kisspeptin monoclonal antibody blocked the estrogen-induced LH surge, indicating that endogenous metastin/kisspeptin released around the POA mediates the estrogen positive feedback effect on GnRH/LH release. Metastin/kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) may be responsible for mediating the feedback effect because the percentage of c-Fos-expressing KiSS-1 mRNA-positive cells to total KiSS-1 mRNA-positive cells was significantly higher in the afternoon than in the morning in the anteroventral periventricular nucleus (AVPV) of high estradiol (E-2)-treated females. The percentage of c-Fos-expressing metastin/kisspeptin neurons was not different between the afternoon and morning in the arcuate nucleus (ARC). Most of the KiSS-1 mRNA expressing cells contain ER alpha immunoreactivity in the AVPV and ARC. In addition, AVPV KiSS-1 mRNA expressions were highest in the proestrous afternoon and lowest in the diestrus 1 in females and were increased by estrogen treatment in ovariectomized animals. On the other hand, the ARC KiSS-1 mRNA expressions were highest at diestrus 2 and lowest at proestrous afternoon and were increased by ovariectomy and decreased by high estrogen treatment. Males lacking the surge mode of GnRH/LH release showed no obvious cluster of metastin/kisspeptin-immunoreactive neurons in the AVPV when compared with high E-2-treated females, which showed a much greater density of these neurons. Taken together, the present study demonstrates that the AVPV metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges in female rats.