The Integrated Hypothalamic Tachykinin-Kisspeptin System as a Central Coordinator for Reproduction
The Integrated Hypothalamic Tachykinin-Kisspeptin System as a Central Coordinator for Reproduction
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DOI：
10.1210/en.2014-1651
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发表时间：
2015-02-01
期刊：
影响因子：
4.8
通讯作者：
Kaiser, Ursula B.
中科院分区：
文献类型：
--
作者：
Navarro, Vctor M.;Bosch, Martha A.;Kaiser, Ursula B.
速激肽由相关肽家族、P 物质 (SP)、神经激肽 A (NKA) 和神经激肽 B (NKB) 组成。 NKB 已成为弓状核 (ARC) 中 Kisspeptin 释放的调节因子，而 SP 和 NKA 在生殖中的作用仍不清楚。这项工作探讨了 SP 和 NKA 在 GnRH 释放的中枢调节中的作用。首先，中央输注针对SP（神经激肽受体1，NK1R）、NKA（NK2R）和NKB（NK3R）受体的特异性激动剂，分别在成年雄性和切除卵巢、雌二醇替代的雌性小鼠中诱导促性腺激素释放，而在Kiss1r（-/-）小鼠中不存在这种情况，表明其具有Kisspeptin依赖性作用。然而，NK2R 激动剂减少了卵巢切除假手术替代雌性体内的 LH 释放，正如 NK3R 激动剂所记录的那样，但与 NK1R 激动剂相反，后者进一步增加了 LH 释放。其次，ARC 和腹内侧核中的 Tac1（编码 SP 和 NKA）表达受到循环雌二醇的抑制，但不与 Kiss1 mRNA 共定位。第三，大约一半的分离的 ARC Kiss1 神经元表达 Tacr1 (NK1R) 和 100% Tacr3 (NK3R)；对于前腹侧-室周 Kiss1 神经元和 GnRH 神经元，大约四分之一表达 Tacr1，十分之一表达 Tacr3；所有病例中均不存在 Tacr2 (NK2R) 表达。总体而言，这些结果确定了在 Kisspeptin-Kiss1r 信号存在的情况下，SP/NK1R 和 NKA/NK2R 系统对促性腺激素释放的有效调节，表明它们可能与 NKB/NK3R 一起控制 GnRH 释放，至少部分是通过对 Kiss1 神经元的作用。
Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r(-/-) mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreased LH release in ovariectomized-sham replaced females, as documented for NK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons and GnRH neurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.