title: 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.
authors.affiliation: Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Jorge Humberto
authors.initials: JH
authors.lastname: Mukdsi
authors.forename: Ana Lucía
authors.initials: AL
authors.lastname: De Paul
authors.forename: Silvina
authors.initials: S
authors.lastname: Gutiérrez
authors.forename: Félix Daniel
authors.initials: FD
authors.lastname: Roth
authors.forename: Agustín
authors.initials: A
authors.lastname: Aoki
authors.forename: Alicia Inés
authors.initials: AI
authors.lastname: Torres
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002457:Cell Extracts; D002467:Cell Nucleus / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D007150:Immunohistochemistry; D052682:Lactotrophs / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D015175:Prolactinoma / Q000139:chemically induced / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D002457:Cell Extracts; D004967:Estrogens; D042461:Vascular Endothelial Growth Factor A