Rogers M C, Silverman A J, Gibson M J
Fishberg Center for Neurobiology and Division of Endocrinology, Mount Sinai School of Medicine, New York, New York, 10029, USA.
Exp Neurol. 1998 Jun;151(2):265-72. doi: 10.1006/exnr.1998.6805.
Gonadotropin-releasing hormone (GnRH) axons project to the median eminence, where the peptide is released to stimulate pituitary gonadotrophs. Hypogonadal mice (hpg) do not synthesize GnRH due to a deletion in the gene. When neonatal preoptic area (POA) tissue from normal mice containing GnRH neurons is transplanted into the third ventricle of hpg mice, GnRH axons exit the graft and specifically project to the median eminence, where the release of GnRH in the portal circulation induces the stimulation of the pituitary-gonadal axis. To test the hypothesis that the median eminence region is critical to targeting, we placed POA grafts in the region of the mammillary bodies, which never contains GnRH cell bodies, but is nevertheless close to the median eminence. Control mice received bilateral grafts into the anterior hypothalamus. GnRH axons innervated the median eminence in animals with grafts in the mammillary bodies and posterior hypothalamus. Mice with such grafts for 4-5 months had gonadal development, while those with grafts for shorter periods did not. Anterior hypothalamic grafts merged into the third ventricle and, consistent with previous studies, this resulted in GnRH innervation of the median eminence and gonadal development. However, when grafts were located within dorsal regions such as the thalamus, no median eminence innervation was seen. In these cases, GnRH axons borrowed other bundles of fibers to travel within the host brain. The pattern of innervation from grafts within ventro-caudal regions of the hypothalamus vs. that from dorsal regions supported the hypothesis that the median eminence releases diffusible substances directing GnRH outgrowth.
促性腺激素释放激素（GnRH）轴突投射至正中隆起，在此处该肽被释放以刺激垂体促性腺细胞。性腺功能减退小鼠（hpg）由于基因缺失而无法合成GnRH。当将来自正常小鼠含有GnRH神经元的视前区（POA）新生组织移植到hpg小鼠的第三脑室内时，GnRH轴突离开移植物并特异性地投射至正中隆起，在门脉循环中GnRH的释放在此处诱导垂体 - 性腺轴的刺激。为了检验正中隆起区域对于靶向定位至关重要这一假说，我们将POA移植物置于乳头体区域，该区域从未含有GnRH细胞体，但仍靠近正中隆起。对照小鼠接受双侧移植物植入下丘脑前部。在乳头体和下丘脑后部植入移植物的动物中，GnRH轴突支配正中隆起。植入此类移植物4 - 5个月的小鼠出现性腺发育，而植入时间较短的小鼠则未出现。下丘脑前部移植物融入第三脑室，与先前研究一致，这导致GnRH支配正中隆起并出现性腺发育。然而，当移植物位于丘脑等背侧区域时，未观察到正中隆起的神经支配。在这些情况下，GnRH轴突借助其他纤维束在宿主脑内穿行。下丘脑腹侧 - 尾侧区域移植物与背侧区域移植物的神经支配模式支持了正中隆起释放可扩散物质引导GnRH生长的假说。
