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 p ituitary. Eight nontumorous pituitaries were investigated by histology, imm unocytochemistry, double immunostaining, and immunoelectron microscopy. Immunocytochemistry, including double immunostaining, showed VEGF immunorea ctive cells to be distributed throughout the adenohypophysis. Immunopositiv ity was evident in all adenohypophysial cell types, but was colocalized mai nly with somatotroph and stellate cell antigen (i.e., growth hormone and S- 100 protein). Weak to moderate VEGF immunoreactivity was also noted in post erior lobe pituicytes as well as in most endothelial and perivascular smoot h muscle cells. In situ hybridization confirmed these findings in demonstra ting a strong signal in corticotrophs, somatotrophs, and stellate cells. Im munoelectron microscopy showed VEGF to be present mainly within secretory g ranules where it colocalized with the full spectrum of adenohypophysial hor mones. The subcellular distribution of VEGF suggests that hypothalamic fact ors play a role in its release from adenohypophysial cells. Further studies are required to examine the possible role of VEGF in affecting both the pi tuitary's vasculature and endocrine activity.