Subcellular localisation of VEGF in different pituitary cells. Changes of its expression in oestrogen induced prolactinomas

Abstract

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.

Activation of multiple growth factor signalling pathways is frequent in meningiomas

“…The findings in our study support the findings in previous reports, but in addition indicate that co‐expression of multiple and, importantly, activated growth factor‐receptor pathways, is a common feature of meningiomas. Most previous studies have assessed both cytoplasmic and membrane receptor immunoreactivity, and although the significance of the nuclear immunoreactivity is unclear, this has also been seen in previous studies on meningiomas, and nuclear localization has also been reported for growth factor receptors in non‐neoplastic tissues …”

VEGF and CD31 Association in Pituitary Adenomas

“…Vascular endothelial growth factor (VEGF) plays a pivotal role as an angiogenic promoter by stimulating endothelial cells proliferation and migration and enhancing vascular permeability. VEGF expression has been described in all cell types in the normal pituitary, with greater expression in somatotroph and follicle-stellate cells [9,10]. In a group of pituitary adenomas, ACTH-and GH-secreting adenomas and pituitary carcinomas had the strongest VEGF immunoreactivity [11].…”

Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane

“…, 1993). The intracellular localization of VEGF has been also studied extensively, but mostly on the target cells, where internalization of the molecule and its appearance in the nucleus has also been reported (Li and Keller, 2000; Mukdsi et al. , 2005; Eichmann and Simons, 2012; Liu et al.…”