Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard Dallas, TX, USA.
Neuroscience. 2011 Jan 26;173:37-56. doi: 10.1016/j.neuroscience.2010.11.022. Epub 2010 Nov 18.
Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or β-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed melanocortin receptors type 4 (MC4R). Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction.
由于促性腺激素释放激素不足性性腺功能减退症，缺失编码 kisspeptins（Kiss1）或 kisspeptin 受体（Kiss1r）的基因功能的人类和小鼠均不育。在下丘脑内，Kiss1 mRNA 在腹前室旁核（AVPV）和弓状核（Arc）中表达。为了更好地研究 kisspeptin 细胞的不同群体，我们生成了 Kiss1-Cre 转基因小鼠。通过生成依赖 Cre 表达绿色荧光蛋白或β-半乳糖苷酶的小鼠，我们获得了一条具有 Kiss1 神经元中 Cre 活性的特定线（J2-4 线）。此外，我们在大脑皮层中证实了 Kiss1 的表达，并证实了先前的数据显示 Kiss1 mRNA 在杏仁核中间核和前背侧视前核中表达。Kiss1 神经元在 Arc 的尾部水平更加集中，并且在 Arc 的最尾部 Kiss1 神经元群体中观察到更高的瘦素反应性。没有观察到瘦素对 AVPV Kiss1 神经元的直接作用的证据。黑色素皮质素纤维支配视前区和 Arc 的 Kiss1 神经元的亚群，并且这两个群体都表达黑色素皮质素受体 4（MC4R）。特别是在视前区，18-28%的 Kiss1 神经元表达 MC4R。在 Arc 中，90%的 Kiss1 神经元为谷氨酸能，其中 50%也是 GABA 能。在 AVPV 中，20%的 Kiss1 神经元为谷氨酸能，而 75%为 GABA 能。视前区和 Arc 中的 Kiss1 神经元之间观察到的差异可能代表了它们在代谢和生殖中作用不同的神经元证据。
