Localization of vascular endothelial growth factor in nontumorous human pituitaries

Vascular endothelial growth factor (VEGF) is a key mediator of endothelial cell proliferation, angiogenesis, and vascular permeability. Our aim was to investigate whether VEGF is expressed in various cell types of the human pituitary. Eight nontumorous pituitaries were investigated by histology, immunocytochemistry, double immunostaining, and immunoelectron microscopy.Immunocytochemistry, including double immunostaining, showed VEGF immunoreactive cells to be distributed throughout the adenohypophysis. Immunopositivity was evident in all adenohypophysial cell types, but was colocalized mainly with somatotroph and stellate cell antigen (i.e., growth hormone and S-100 protein). Weak to moderate VEGF immunoreactivity was also noted in posterior lobe pituicytes as well as in most endothelial and perivascular smooth muscle cells.In situ hybridization confirmed these findings in demonstrating a strong signal in corticotrophs, somatotrophs, and stellate cells. Immunoelectron microscopy showed VEGF to be present mainly within secretory granules where it colocalized with the full spectrum of adenohypophysial hormones. The subcellular distribution of VEGF suggests that hypothalamic factors play a role in its release from adenohypophysial cells. Further studies are required to examine the possible role of VEGF in affecting both the pituitary's vasculature and endocrine activity.