Radovick S, Wray S, Lee E, Nicols D K, Nakayama Y, Weintraub B D, Westphal H, Cutler G B, Wondisford F E
Department of Pediatrics, University Hospitals of Cleveland, Case Western Reserve University, OH 44106.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3402-6. doi: 10.1073/pnas.88.8.3402.
Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be caused by failure in normal migration of GnRH neurons to the hypothalamus. We report that in transgenic mice expression of the simian virus 40 T antigen, driven by the promoter of human GnRH gene, resulted in central hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway. This system appears to be an important animal model of hypogonadotropic hypogonadism in humans. Additionally, olfactory bulb tumors from these animals were dispersed, and a GnRH-secreting neuronal cell line (GN cell line) was established.
促性腺激素释放激素（GnRH）在生殖过程中起着重要作用，尽管人类中枢性性腺功能减退的机制尚不清楚。由于GnRH神经元起源于嗅基板，并在发育过程中迁移至下丘脑，因此人类中枢性性腺功能减退可能是由于GnRH神经元向下丘脑的正常迁移失败所致。我们报告称，在转基因小鼠中，由人类GnRH基因启动子驱动的猿猴病毒40 T抗原的表达，导致了中枢性性腺功能减退，这是由于发育过程中神经元迁移停滞以及沿迁移途径形成肿瘤所致。该系统似乎是人类低促性腺激素性性腺功能减退的重要动物模型。此外，这些动物的嗅球肿瘤呈分散状，并且建立了一种分泌GnRH的神经元细胞系（GN细胞系）。
