Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
Endocrinology. 2011 Nov;152(11):4265-75. doi: 10.1210/en.2011-1143. Epub 2011 Sep 13.
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 17β-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.
Kisspeptin (Kiss1) 和神经激肽 B (NKB)（分别由 Kiss1 和 Tac2 基因编码）对生殖至关重要。在许多物种的雌性中，弓状核 (ARC) 中的 Kiss1 神经元共同表达强啡肽 A 和 NKB。这些细胞被称为 Kiss1/NKB/强啡肽 (KNDy) 神经元，被认为介导了 17β-雌二醇对 GnRH/LH 分泌的负反馈调节。然而，我们对雄性 ARC 中 Kiss1/Kiss1 表达神经元的分子生理学和调节知之甚少。我们的工作集中在成年雄性小鼠上，在那里我们寻找 ARC 中这些神经肽在细胞中共表达的证据，评估 Kiss1 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 Kiss1、NKB 和强啡肽的 mRNA 在位于 ARC 的神经元中共表达；2）Kiss1 和强啡肽 A mRNA 通过雌激素和雄激素受体依赖途径受 T 调节；3）senktide，一种 NKB 受体（由 Tacr3 编码的神经激肽 3 受体）激动剂，刺激促性腺激素分泌；4）KNDy 神经元表达 Tacr3，而 GnRH 神经元不表达；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 分泌的负反馈作用中的假定作用，并提供了证据表明，从 KNDy 神经元释放的 NKB 是产生雄性中 Kiss1 和 GnRH 脉冲分泌的自动反馈回路的一部分。
