Brain Research Institute, School of Medicine and Health Sciences, Monash University Sunway Campus, Petaling Jaya 46150, Selangor, Malaysia.
Endocrinology. 2012 May;153(5):2398-407. doi: 10.1210/en.2012-1062. Epub 2012 Mar 27.
The Kiss1/KISS1 gene has recently been implicated as a potent hypothalamic regulator of reproductive functions, in particular, the onset of puberty in mammals. In zebrafish (Danio rerio), there are two kiss1 homologues (kiss1 and kiss2) expressed in the brain: Kiss2-expressing neurons in the hypothalamic nuclei are considered potent regulators of reproduction, whereas the role of Kiss1-expressing neurons in the habenula remains unknown. We first analyzed the expression of kiss1 mRNA in a transgenic zebrafish, in which the habenula-interpeduncular nucleus (IPN) pathway is labelled with green fluorescent protein, and our application of a biocytin neural tracer into the habenula showed the presence of neuronal projections of Kiss1 neurons to the ventral IPN. Therefore, we speculated that kiss1 neurons might regulate the serotonergic system in the raphe. However, laser microdissection followed by real-time PCR revealed the expression of Kiss1 receptor (kissr1) mRNA in the habenula and the ventral IPN but not in the dorsal IPN or the serotonergic neurons in the raphe nuclei. Dual-fluorescent in situ hybridization revealed the coexpression of kiss1 and kissr1 mRNA in the habenula. Administration of Kiss1 significantly decreased the level of kiss1 mRNA (0.3- to 0.5-fold, P < 0.001), but the level of c-fos mRNA was increased (≈ 3-fold, P < 0.05) in the ventral habenula, suggesting that there is autocrine regulation of the kiss1 gene. Kiss1 administration significantly increased the c-fos mRNA levels in the raphe nuclei (2.5-fold, P < 0.001) and genes involved in the regulation of serotonin levels (pet1 and slc6a4a; 3.3- and 2.2-fold, P < 0.01). These findings suggest that the autocrine-regulated habenular Kiss1 neurons indirectly regulate the serotonergic system in the raphe nuclei through the IPN in the zebrafish.
Kiss1/KISS1 基因最近被认为是调节生殖功能的强有力的下丘脑调节剂，特别是在哺乳动物中青春期的开始。在斑马鱼（Danio rerio）中，有两个 kiss1 同源物（kiss1 和 kiss2）在大脑中表达：下丘脑核中的 Kiss2 表达神经元被认为是生殖的有力调节剂，而在缰核中 Kiss1 表达神经元的作用尚不清楚。我们首先分析了在转基因斑马鱼中 kiss1 mRNA 的表达，其中缰核-中脑脚间核（IPN）通路用绿色荧光蛋白标记，我们将生物素化神经示踪剂应用于缰核，显示 Kiss1 神经元的神经元投射到 IPN 的腹侧。因此，我们推测 kiss1 神经元可能调节中缝核的 5-羟色胺能系统。然而，激光微切割后实时 PCR 显示 Kiss1 受体（kissr1）mRNA 在缰核和 IPN 的腹侧表达，但不在 IPN 的背侧或中缝核的 5-羟色胺能神经元中表达。双重荧光原位杂交显示 kiss1 和 kissr1 mRNA 在缰核中共表达。Kiss1 的给药显著降低了缰核中 kiss1 mRNA 的水平（0.3-0.5 倍，P < 0.001），但 c-fos mRNA 的水平增加（≈3 倍，P < 0.05），提示 kiss1 基因存在自分泌调节。Kiss1 的给药显著增加了中缝核中 c-fos mRNA 的水平（2.5 倍，P < 0.001）和参与调节 5-羟色胺水平的基因（pet1 和 slc6a4a；3.3-和 2.2 倍，P < 0.01）。这些发现表明，缰核中的自分泌调节的 Kiss1 神经元通过 IPN 间接调节中缝核中的 5-羟色胺能系统。
