Kisspeptin神经元网络：电针调节青春期PCOS神经内分泌异常的靶点环节？

The onset of polycystic ovarian syndrome (PCOS) is usually in adolescence. Adolescence is a phase during which hypothalamus-pituitary-ovary axis (HPOA) is developing and full of strong plasticity. Therefore, it will delay, inhibit, or even reverse the development of PCOS if we treat PCOS as early as in adolescence. The characteristic neuroendocrine abnormality of adolescent PCOS is over-stimulation of GnRH neuron in hypothalamus. Kisspeptin neuron is the key intermedia to relay all kinds of signals to GnRH neuron. This project speculate that abnormal onset of adolescence with too strong excitatory signals and/or too weak inhibitory signals which makes too much secretion and/or too strong effect of kisspeptin, is the important mechanism of GnRH neuron over-stimulation in adolescent PCOS; electro-acupuncture (EA), as a kind of stimulatory signal, can inhibit the over-stimulation of GnRH neuron through regulating kisspeptin neuron network, and then improve neuroendocrine abnormality of adolescent PCOS. Utilizing techniques of real-time RT-PCR, western blot, in situ hybridization and double-labbed immunofluorescence combined with confocal microscopy, the project will probe the mechanisms of EA in regulating neuroendocrine abnormality in adolescent PCOS from the target point of kisspeptin neuron network including presynaptic and postsynaptic signaling pathways.

PCOS多起病于青春期，此时HPOA具有很强的可塑性，及早在青春期对PCOS进行干预，可延缓、抑制甚或逆转其发展。青春期PCOS典型的神经内分泌异常就是下丘脑GnRH神经元的过度激活。Kisspeptin神经元是机体将各种信号传递给GnRH神经元的关键媒介。本项目推测，青春期启动异常，兴奋性信号过度增强和/或抑制性信号过度减弱，使得Kisspeptin分泌增多或作用增强，是导致青春期PCOS的GnRH神经元过度激活的重要机制；电针作为一种刺激信号，通过调节Kisspeptin神经元网络抑制GnRH神经元的过度激活，从而改善青春期PCOS的神经内分泌异常。本项目采用实时定量RT-PCR技术、Western blot法、原位杂交技术、免疫荧光双标记结合激光共聚焦显微技术，以Kisspeptin神经元网络（突触前和突触后信号通路两方面）为靶点，探讨电针调节青春期PCOS神经内分泌异常的作用机制。