Inserm U693, faculté de médecine Paris-Sud, université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France.
Ann Endocrinol (Paris). 2012 Nov;73(5):448-58. doi: 10.1016/j.ando.2012.07.680. Epub 2012 Sep 20.
Since 2003, kisspeptin and its receptor (KISS1R, also called GPR54) are recognized as major actors of the gonadotrope axis. Mutations of genes encoding the peptide or the receptor have been identified in patients with precocious puberty or hypogonadotropic hypogonadism. They are strong stimulators of GnRH neurons and are involved in various mechanisms regulating gonadotrope axis as puberty induction or positive and negative feedback regulation on the gonadotrope axis by gonadal steroids. They also mediated some metabolic or environmental signals on the reproduction axis. Kisspeptins are synthesized and secreted by hypothalamic nuclei located in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). This system is complex because neurons located in the ARC coexpress many neuromediators such as neurokinin B and dynorphin, involved in the control of gonadotrope axis. During pregnancy, kisspeptins are also secreted by placenta and should be involved in trophoblastic invasion. After kisspeptin administration to male and female animals as well as to women with hypothalamic secondary amenorrhoea, they are able to stimulate GnRH and gonadotrophin secretion. Then, kisspeptin agonists appear as valuable new tools in treatment for reproduction troubles. The aim of this review is to clarify the role of kisspeptins in regulating gonadotrophin secretion and explores their possible therapeutic use.
自 2003 年以来，kisspeptin 及其受体（KISS1R，也称为 GPR54）被认为是性腺轴的主要调节因子。编码该肽或受体的基因突变已在性早熟或促性腺激素低下性性腺功能减退症患者中被发现。它们是 GnRH 神经元的强刺激物，参与调节性腺轴的各种机制，如诱导青春期或通过性腺类固醇对性腺轴的正、负反馈调节。它们还介导生殖轴上的一些代谢或环境信号。Kisspeptin 由位于弓状核（ARC）和前脑室下核（AVPV）的下丘脑核合成和分泌。该系统很复杂，因为位于 ARC 的神经元共表达许多神经递质，如神经激肽 B 和强啡肽，参与对性腺轴的控制。在怀孕期间，胎盘也会分泌 kisspeptin，应该参与滋养层的侵袭。在给雄性和雌性动物以及患有下丘脑性继发性闭经的女性施用 kisspeptin 后，它们能够刺激 GnRH 和促性腺激素的分泌。然后，kisspeptin 激动剂作为治疗生殖障碍的有价值的新工具出现。本文综述的目的是阐明 kisspeptin 在调节促性腺激素分泌中的作用，并探讨其可能的治疗用途。
