Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
Endocrinology. 2012 Apr;153(4):1717-24. doi: 10.1210/en.2011-1937. Epub 2012 Feb 21.
The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this study, we attempted to discover the factor that induces interconnection of FS cells and succeeded in identifying chemokine (CXC)-L12 and its receptor CXCR4 as potential candidate molecules. CXCL12 is a chemokine of the CXC subfamily. It exerts its effects via CXCR4, a G protein-coupled receptor. The CXCL12/CXCR4 axis is a potent chemoattractant for many types of neural cells. First, we revealed that CXCL12 and CXCR4 are expressed by FS cells in rat anterior pituitary gland. Next, to clarify the function of the CXCL12/CXCR4 axis in FS cells, we observed living anterior pituitary cells in primary culture with specific CXCL12 inhibitor or CXCR4 antagonist and noted that extension of cytoplasmic processes and interconnection of FS cells were inhibited. Finally, we examined FS cell migration and invasion by using Matrigel matrix assays. CXCL12 treatment resulted in markedly increased FS cell migration and invasion. These data suggest that FS cells express chemokine CXCL12 and its receptor CXCR4 and that the CXCL12/CXCR4 axis evokes interconnection of FS cells.
垂体前叶由五种产生激素的细胞类型加上卵泡星形（FS）细胞组成，后者不产生经典的垂体前叶激素。FS 细胞通过细胞质过程相互连接，并环绕产生激素的细胞或同种聚集。使用原代培养的活细胞成像，我们最近报道，一些 FS 细胞精确地将其细胞质过程延伸到其他 FS 细胞，并与之形成连接。这些现象表明存在促进连接的趋化因子因素。在这项研究中，我们试图发现诱导 FS 细胞连接的因子，并成功地鉴定趋化因子（CXC）-L12 和其受体 CXCR4 作为潜在的候选分子。CXCL12 是 CXC 亚家族的趋化因子。它通过 G 蛋白偶联受体 CXCR4 发挥作用。CXCL12/CXCR4 轴是许多类型的神经细胞的有效趋化因子。首先，我们揭示了 FS 细胞在大鼠垂体前叶中表达 CXCL12 和 CXCR4。接下来，为了阐明 CXCL12/CXCR4 轴在 FS 细胞中的功能，我们观察了原代培养中的活垂体前体细胞，并用特定的 CXCL12 抑制剂或 CXCR4 拮抗剂，并注意到 FS 细胞的细胞质过程延伸和连接被抑制。最后，我们通过使用 Matrigel 基质测定法检查了 FS 细胞的迁移和侵袭。CXCL12 处理导致 FS 细胞迁移和侵袭明显增加。这些数据表明 FS 细胞表达趋化因子 CXCL12 和其受体 CXCR4，并且 CXCL12/CXCR4 轴引发 FS 细胞的连接。
