Navratil Amy M, Knoll J Gabriel, Whitesell Jennifer D, Tobet Stuart A, Clay Colin M
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093, USA.
Endocrinology. 2007 Apr;148(4):1736-44. doi: 10.1210/en.2006-1153. Epub 2007 Jan 11.
The secretion of LH is cued by the hypothalamic neuropeptide, GnRH. After delivery to the anterior pituitary gland via the hypothalamic-pituitary portal vasculature, GnRH binds to specific high-affinity receptors on the surface of gonadotrope cells and stimulates synthesis and secretion of the gonadotropins, FSH, and LH. In the current study, GnRH caused acute and dramatic changes in cellular morphology in the gonadotrope-derived alphaT3-1 cell line, which appeared to be mediated by engagement of the actin cytoskeleton; disruption of actin with jasplakinolide abrogated cell movement and GnRH-induced activation of ERK. In live murine pituitary slices infected with an adenovirus-containing Rous sarcoma virus-green fluorescent protein, selected cells responded to GnRH by altering their cellular movements characterized by both formation and extension of cell processes and, surprisingly, spatial repositioning. Consistent with the latter observation, GnRH stimulation increased the migration of dissociated pituitary cells in transwell chambers. Our data using live pituitary slices are a striking example of neuropeptide-evoked movements of cells outside the central nervous system and in a mature peripheral endocrine organ. These findings call for a fundamental change in the current dogma of simple passive diffusion of LH from gonadotropes to capillaries in the pituitary gland.
促黄体生成素(LH)的分泌由下丘脑神经肽促性腺激素释放激素(GnRH)引发。GnRH通过下丘脑 - 垂体门脉血管系统输送至腺垂体后,与促性腺激素细胞表面的特异性高亲和力受体结合,刺激促性腺激素卵泡刺激素(FSH)和LH的合成与分泌。在本研究中,GnRH导致促性腺激素来源的αT3 - 1细胞系的细胞形态发生急性且显著的变化,这似乎是由肌动蛋白细胞骨架的参与介导的;用茉莉酸内酯破坏肌动蛋白可消除细胞运动以及GnRH诱导的细胞外信号调节激酶(ERK)激活。在感染含劳斯肉瘤病毒 - 绿色荧光蛋白腺病毒的活小鼠垂体切片中,选定的细胞通过改变其细胞运动对GnRH作出反应,其特征为细胞突起的形成和延伸,并且令人惊讶的是还有空间重新定位。与后一观察结果一致,GnRH刺激增加了Transwell小室中解离的垂体细胞的迁移。我们使用活垂体切片的数据是神经肽引发中枢神经系统外和成熟外周内分泌器官中细胞运动的一个显著例子。这些发现要求对当前关于LH在垂体中从促性腺激素细胞简单被动扩散至毛细血管的教条进行根本性改变。