Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats
Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats
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DOI：
10.1210/en.2005-0195
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发表时间：
2005-10-01
期刊：
影响因子：
4.8
通讯作者：
Maeda, KI
中科院分区：
文献类型：
--
作者：
Kinoshita, M;Tsukamura, H;Maeda, KI
排卵是由一系列神经内分泌事件引起的：成熟卵泡分泌的雌激素的正反馈作用诱导GnRH和LH激增。然而，雌激素对促性腺激素释放激素/促黄体生成素分泌的正反馈作用的中心机制尚不完全清楚。本研究探讨转移抑制基因KiSS-1的产物Metastin是否是调节雌性大鼠GnRH/LH峰进而动情周期的中枢神经肽。在雌激素诱导的去卵巢大鼠中，向第三脑室注射Metastin或注射Metastin后，可通过作用于大多数投射到正中隆起的GnRH神经元所在的视前区(POA)，对黄体生成素的分泌产生深刻的刺激作用。用免疫组织化学方法在弓状核(ARC)发现Metastin神经元与雌激素受体共存，视前区(POA)内的一些纤维与GnRH神经元胞体或纤维紧密结合。定量RT-PCR结果表明，KiSS-1和GPr54mRNAs分别在ARC和POA中表达。用抗大鼠Metastin的特异性单抗阻断POA的局部Metastin作用，可完全消除发情前的黄体生成素峰，抑制发情周期。与发情间期相比，午后发情前期ARC内Metastin免疫反应阳性胞体明显增加，c-Fos表达明显增强。因此，POA中释放的Metastin参与了诱导排卵前的LH峰和调节发情周期。
Ovulation is caused by a sequence of neuroendocrine events: GnRH and LH surges that are induced by positive feedback action of estrogen secreted by the mature ovarian follicles. The central mechanism of positive feedback action of estrogen on GnRH/LH secretion, however, is not fully understood yet. The present study examined whether metastin, the product of metastasis suppressor gene KiSS-1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Metastin had a profound stimulation on LH secretion by acting on the preoptic area (POA), where most GnRH neurons projecting to the median eminence are located, because injection of metastin into the third ventricle or POA increased plasma LH concentrations in estrogen-primed ovariectomized rats. Metastin neurons were immunohistochemically found in the arcuate nucleus (ARC) to be colocalized with estrogen receptors with some fibers in the preoptic area (POA) in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR has revealed that KiSS-1 and GPR54 mRNAs were expressed in the ARC and POA, respectively. The blockade of local metastin action in the POA with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. Metastin-immunoreactive cell bodies in the ARC showed a marked increase and c-Fos expression in the early proestrus afternoon compared with the day of diestrus. Thus, metastin released in the POA is involved in inducing the pre-ovulatory LH surge and regulating estrous cyclicity.