Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (Oryzias latipes)
Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (Oryzias latipes)
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DOI：
10.1210/en.2007-1503
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发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Oka, Yoshitaka
中科院分区：
文献类型：
--
作者：
Kanda, Shinji;Akazome, Yasuhisa;Oka, Yoshitaka
最近，一种新的生理活性肽kisspeptin （metastin）被报道通过直接刺激几种哺乳动物的GnRH神经元来促进性成熟和排卵。尽管kisspeptin神经元在生殖的神经内分泌调节中具有重要作用，但目前仅在哺乳动物中进行了研究，在非哺乳动物脊椎动物中尚无关于kisspeptin或kisspeptin神经系统的报道。我们使用medaka对KiSS-1基因进行了初步鉴定，并对非哺乳动物大脑中表达KiSS-1 mRNA的神经元（KiSS-1神经元）的解剖分布进行了分析。对克隆的medaka KiSS-1基因进行原位杂交，证实了两个kisspeptin神经元群定位于下丘脑核、后脑室周围核和结节腹侧核。此外，在繁殖条件下，NVT KiSS-1神经元在数量上呈两性二态（雄性神经元>，雌性神经元>）。我们还发现，卵巢雌激素正调控吻1神经元的数量在NVT，而不是在脑室周围后核。在繁殖和非繁殖条件下，NVT中KiSS-1神经元的数量存在明显差异，这一事实强烈表明，NVT中KiSS-1 mRNA表达的类固醇敏感性变化是根据生殖状态的变化而发生的生理变化。综上所述，medaka KiSS-1神经元系统参与了生殖功能的中枢调节，并且由于其具有许多实验优势，可以作为一个很好的模型系统来研究medaka大脑的生理学。
Recently, a novel physiologically active peptide, kisspeptin (metastin), has been reported to facilitate sexual maturation and ovulation by directly stimulating GnRH neurons in several mammalian species. Despite its importance in the neuroendocrine regulation of reproduction, kisspeptin neurons have only been studied in mammals, and there has been no report on the kisspeptin or kisspeptin neuronal systems in nonmammalian vertebrates. We used medaka for the initial identification of the KiSS-1 gene and the anatomical distribution of KiSS-1 mRNA expressing neurons (KiSS-1 neurons) in the brain of nonmammalian species. In situ hybridization for the medaka KiSS-1 gene cloned here proved that two kisspeptin neuronal populations are localized in the hypothalamic nuclei, the nucleus posterioris periventricularis and the nucleus ventral tuberis (NVT). Furthermore, NVT KiSS-1 neurons were sexually dimorphic in number (male neurons >> female neurons) under the breeding conditions. We also found that the number of KiSS-1 neurons in the NVT but not that in the nucleus posterioris periventricularis was positively regulated by ovarian estrogens. The fact that there were clear differences in the number of NVT KiSS-1 neurons between the fish under the breeding and nonbreeding conditions strongly suggests that the steroid-sensitive changes in the KiSS-1 mRNA expression in the NVT occur physiologically, according to the changes in the reproductive state. From the present results, we conclude that the medaka KiSS-1 neuronal system is involved in the central regulation of reproductive functions, and, given many experimental advantages, the medaka brain may serve as a good model system to study its physiology.