Mukdsi Jorge Humberto, De Paul Ana Lucía, Gutiérrez Silvina, Roth Félix Daniel, Aoki Agustín, Torres Alicia Inés
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
J Mol Histol. 2005 Oct;36(8-9):447-54. doi: 10.1007/s10735-005-9012-7. Epub 2006 May 19.
Vascular endothelial growth factor (VEGF) is an important angiogenic factor in the pituitary gland. The objective of this study was to unveil the VEGF subcellular localisation in different pituitary cell types and to evaluate changes in its expression at different time intervals after oestrogen stimulation. A relevant feature demonstrated was the identification of this cytokine in the nucleus and cytoplasm of lactotrophs, somatotrophs and gonadotrophs, as well as in follicle-stellate cells of male rats. Oestrogen treatment increased the number of VEGF immunopositive cells and its expression detected differentially by western blot in both nucleus and cytoplasm of pituitary cells when compared to the control. At ultrastructural level VEGF appeared associated with nucleolus and euchromatin involving a possible internal autocrine loop. In lactotrophs, the predominant cell of the tumour, VEGF was immunodetected in RER, Golgi complex, and vesicular organelles, supporting further the association with an auto-paracrine effect exerted by VEGF. The nucleus/cytoplasm ratio of VEGF revealed a prevalent accumulation of VEGF in the cytoplasm. The presence of VEGF in the nucleus may probably be associated with a translocation to this cell compartment. This study demonstrated a cytoplasmic and nuclear immunolocalisation of VEGF in normal and tumoural adenohypophyseal cells. In the course of prolactinoma development, the oestrogen stimulated VEGF expression in tumoural cells, promoting a vascular adaptation which contributes to growth and progression of the tumour.
血管内皮生长因子(VEGF)是垂体中一种重要的血管生成因子。本研究的目的是揭示VEGF在不同垂体细胞类型中的亚细胞定位,并评估雌激素刺激后不同时间间隔其表达的变化。所展示的一个相关特征是在雄性大鼠的催乳素细胞、生长激素细胞和促性腺激素细胞的细胞核和细胞质中,以及在卵泡星状细胞中鉴定出了这种细胞因子。与对照组相比,雌激素处理增加了VEGF免疫阳性细胞的数量及其在垂体细胞的细胞核和细胞质中通过蛋白质印迹法差异检测到的表达。在超微结构水平上,VEGF似乎与核仁和常染色质相关,涉及一个可能的内部自分泌环。在肿瘤的主要细胞——催乳素细胞中,在粗面内质网、高尔基体和泡状细胞器中检测到VEGF免疫反应,进一步支持了VEGF发挥的自分泌旁分泌作用。VEGF的细胞核/细胞质比值显示VEGF在细胞质中普遍积累。VEGF在细胞核中的存在可能与向该细胞区室的转运有关。本研究证明了VEGF在正常和肿瘤性腺垂体细胞中的细胞质和细胞核免疫定位。在催乳素瘤发展过程中,雌激素刺激肿瘤细胞中VEGF的表达,促进血管适应,这有助于肿瘤的生长和进展。