Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus)
Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus)
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DOI：
10.1073/pnas.1113035108
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发表时间：
2011-10-18
影响因子：
11.1
通讯作者：
Tsukamura, Hiroko
中科院分区：
文献类型：
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作者：
Inoue, Naoko;Sasagawa, Karin;Tsukamura, Hiroko
本研究调查了 Kisspeptin-G 蛋白偶联受体 54 (GPR54) 信号传导是否在介导麝香鼩 (Suncus murinus)（一种反射性排卵动物）交配诱导排卵中发挥作用。为此，我们从下丘脑克隆了 suncus Kiss1 和 Gpr54 cDNA，发现 suncus Kisspeptin (sKp) 由 29 个氨基酸残基 (sKp-29) 组成。注射外源性 sKp-29 模拟交配刺激，诱导卵泡成熟和排卵。给予几种 Kisspeptins 和 GPR54 激动剂也以剂量依赖性方式诱导推定排卵，并且 Gpr54 mRNA 分布在下丘脑中，表明 Kisspeptins 通过与 GPR54 结合诱导排卵。 sKp-29 诱导的排卵被促性腺激素释放激素 (GnRH) 拮抗剂预处理完全阻断，这表明 Kisspeptin 激活 GnRH 神经元以诱导麝鼩的排卵。此外，原位杂交显示Kiss1表达细胞位于麝鼩下丘脑的内侧视前区（POA）和弓状核。 POA或弓状核中表达Kiss1的细胞数量被雌二醇上调或下调，表明这些区域的Kisspeptin神经元是雌激素反馈作用的目标。最后，交配刺激很大程度上诱导了 POA 中 Kiss1 阳性细胞中的 c-Fos 表达，表明交配刺激激活了 POA Kisspeptin 神经元以诱导排卵。综上所述，这些结果表明，kisspeptin-GPR54 信号传导在麝鼩（反射性排卵者）的排卵诱导中发挥作用，就像在自发排卵者中一样。
The present study investigated whether kisspeptin-G protein-coupled receptor 54 (GPR54) signaling plays a role in mediating mating-induced ovulation in the musk shrew (Suncus murinus), a reflex ovulator. For this purpose, we cloned suncus Kiss1 and Gpr54 cDNA from the hypothalamus and found that suncus kisspeptin (sKp) consists of 29 amino acid residues (sKp-29). Injection of exogenous sKp-29 mimicked the mating stimulus to induce follicular maturation and ovulation. Administration of several kisspeptins and GPR54 agonists also induced presumed ovulation in a dose-dependent manner, and Gpr54 mRNA was distributed in the hypothalamus, showing that kisspeptins induce ovulation through binding to GPR54. The sKp-29-induced ovulation was blocked completely by pretreatment with a gonadotropin-releasing hormone (GnRH) antagonist, suggesting that kisspeptin activates GnRH neurons to induce ovulation in the musk shrew. In addition, in situ hybridization revealed that Kiss1-expressing cells are located in the medial preoptic area (POA) and arcuate nucleus in the musk shrew hypothalamus. The number of Kiss1-expressing cells in the POA or arcuate nucleus was up-regulated or down-regulated by estradiol, suggesting that kisspeptin neurons in these regions were the targets of the estrogen feedback action. Finally, mating stimulus largely induced c-Fos expression in Kiss1-positive cells in the POA, indicating that the mating stimulus activates POA kisspeptin neurons to induce ovulation. Taken together, these results indicate that kisspeptin-GPR54 signaling plays a role in the induction of ovulation in the musk shrew, a reflex ovulator, as it does in spontaneous ovulators.