Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago 8380492, Chile.
Endocrinology. 2012 Oct;153(10):4966-77. doi: 10.1210/en.2012-1279. Epub 2012 Aug 6.
Kisspeptin and its receptor GPR54 have been described as key hypothalamic components in the regulation of GnRH secretion. Kisspeptin is also present in several regions of the central nervous system and the peripheral organs and has recently been identified in the superior ganglion. Herein, we tested the possibility that ovarian kisspeptin is regulated by the sympathetic nervous system and participates locally in the regulation of ovarian function. Both ovarian and celiac ganglion kisspeptin mRNA levels increase during development, whereas kisspeptin peptide levels and plasma levels decrease during development. In the celiac ganglion, kisspeptin colocalized with tyrosine hydroxylase, indicating potential kisspeptin synthesis and transport within the sympathetic neurons. A continuous (64 h) cold stress induced marked changes within the kisspeptin neural system along the celiac ganglion-ovary axis. In vitro incubation with the β-adrenergic agonist isoproterenol increased ovarian kisspeptin mRNA and peptide levels, and this increase was inhibited by treatment with the β-antagonist propranolol. Sectioning the superior ovarian nerve altered the feedback information within the kisspeptin celiac ganglion-ovary axis. In vivo administration of a kisspeptin antagonist to the left ovarian bursa of 22- to 50-d-old unilaterally ovariectomized rats delayed the vaginal opening, decreased the percentage of estrous cyclicity, and decreased plasma, ovarian, and celiac ganglion kisspeptin concentrations but did not modify the LH plasma levels. These results indicate that the intraovarian kisspeptin system may be regulated by sympathetic nerve activity and that the peptide, either from a neural or ovarian origin, is required for proper coordinated ovarian function.
Kisspeptin 及其受体 GPR54 已被描述为调节 GnRH 分泌的下丘脑关键组成部分。Kisspeptin 也存在于中枢神经系统和外周器官的几个区域，并在交感神经节中最近被发现。在此，我们测试了卵巢 kisspeptin 是否受交感神经系统调节并局部参与卵巢功能调节的可能性。卵巢和腹腔神经节 kisspeptin mRNA 水平在发育过程中增加，而 kisspeptin 肽水平和血浆水平在发育过程中降低。在腹腔神经节中，kisspeptin 与酪氨酸羟化酶共定位，表明潜在的 kisspeptin 在交感神经元内合成和运输。持续 64 小时的冷应激会沿着腹腔神经节-卵巢轴引起 kisspeptin 神经系统的明显变化。体外用β-肾上腺素能激动剂异丙肾上腺素孵育会增加卵巢 kisspeptin mRNA 和肽水平，而这种增加被β-拮抗剂普萘洛尔抑制。切断卵巢上神经会改变 kisspeptin 腹腔神经节-卵巢轴内的反馈信息。在 22-50 日龄单侧卵巢切除术大鼠的左侧卵巢囊泡内给予 kisspeptin 拮抗剂，会延迟阴道开口，降低发情周期的百分比，并降低血浆、卵巢和腹腔神经节 kisspeptin 浓度，但不改变 LH 血浆水平。这些结果表明，卵巢内的 kisspeptin 系统可能受交感神经活动调节，并且该肽（来自神经或卵巢）是适当协调卵巢功能所必需的。
