Regulation of NKB Pathways and Their Roles in the Control of Kiss1 Neurons in the Arcuate Nucleus of the Male Mouse
Regulation of NKB Pathways and Their Roles in the Control of Kiss1 Neurons in the Arcuate Nucleus of the Male Mouse
复制标题
DOI：
10.1210/en.2011-1143
复制
发表时间：
2011-11-01
期刊：
影响因子：
4.8
通讯作者：
Steiner, R. A.
中科院分区：
文献类型：
--
作者：
Navarro, V. M.;Gottsch, M. L.;Steiner, R. A.
Kisspeptin（Kiss 1）和神经激肽B（NKB）（分别由Kiss 1和Tac 2基因编码）是生殖所必需的。在许多物种的雌性中，弓状核（ARC）中的Kiss 1神经元共表达强啡肽A和NKB。这种细胞被称为Kiss 1/NKB/强啡肽（KNDy）神经元，其被认为介导17 β-雌二醇对GnRH/LH分泌的负反馈调节。然而，我们对Kiss 1/Kiss 1表达神经元的分子生理学和调控的男性ARC的知识很少。我们的工作集中在成年雄性小鼠，在那里我们寻找这些神经肽在ARC细胞中共表达的证据，评估Kiss 1神经元在睾酮（T）对GnRH/LH分泌的负反馈调节中的作用，并研究NKB对KNDy和GnRH神经元的作用。结果表明：1）编码Kiss 1、NKB和强啡肽的mRNA在位于ARC的神经元中共表达; 2）Kiss 1和强啡肽A mRNA通过雌激素和雄激素受体依赖性途径受到T的调节; 3）NKB受体激动剂senktide（神经激肽3受体，由Tacr 3编码）刺激促性腺激素分泌; 4）KNDy神经元表达Tacr 3，而GnRH神经元不表达;和5）senktide激活KNDy神经元，但对GnRH神经元没有明显影响。这些观察结果证实了KNDy神经元在介导T对GnRH/LH分泌的负反馈效应中的假定作用，并提供了证据表明，从KNDy神经元释放的NKB是在雄性中产生Kiss 1和GnRH脉冲式分泌的自动反馈回路的一部分。（内分泌学152：4265-4275，2011）
Kisspeptin (Kiss1) and neurokinin B (NKB) (encoded by the Kiss1 and Tac2 genes, respectively) are indispensable for reproduction. In the female of many species, Kiss1 neurons in the arcuate nucleus (ARC) coexpress dynorphin A and NKB. Such cells have been termed Kiss1/NKB/Dynorphin (KNDy) neurons, which are thought to mediate the negative feedback regulation of GnRH/LH secretion by 17 beta-estradiol. However, we have less knowledge about the molecular physiology and regulation of Kiss1/Kiss1-expressing neurons in the ARC of the male. Our work focused on the adult male mouse, where we sought evidence for coexpression of these neuropeptides in cells in the ARC, assessed the role of Kiss1 neurons in negative feedback regulation of GnRH/LH secretion by testosterone (T), and investigated the action of NKB on KNDy and GnRH neurons. Results showed that 1) the mRNA encoding Kiss1, NKB, and dynorphin are coexpressed in neurons located in the ARC; 2) Kiss1 and dynorphin A mRNA are regulated by T through estrogen and androgen receptor-dependent pathways; 3) senktide, an agonist for the NKB receptor (neurokinin 3 receptor, encoded by Tacr3), stimulates gonadotropin secretion; 4) KNDy neurons express Tacr3, whereas GnRH neurons do not; and 5) senktide activates KNDy neurons but has no discernable effect on GnRH neurons. These observations corroborate the putative role for KNDy neurons in mediating the negative feedback effects of T on GnRH/LH secretion and provide evidence that NKB released from KNDy neurons is part of an auto-feedback loop that generates the pulsatile secretion of Kiss1 and GnRH in the male. (Endocrinology 152: 4265-4275, 2011)