Induction stage-dependent expression of vascular endothelial growth factor and aquaporin-1 in diethylstilbestrol-treated rat pituitary

The anterior pituitary gland undergoes tumourigenic changes in response to oestrogen treatment in several breeds of rats. We administered diethylstilbestrol (DES) to female Wistar rats and assessed whether the expression of vascular endothelial growth factor (VEGF) and aquaporin-1 (AQP-1) was altered at different time points following DES administration. In vivo magnetic resonance imaging (MRI) scans showed that the mass index corresponding to the mid-sagittal area of DES-treated pituitary was significantly higher than the vehicle-controlled pituitary (p<0.01) at three specific time points, accompanied by a significant reduction in body weight. Haematoxylin and eosin (HE) staining and immunohistochemical analysis demonstrated that during early stages of induction, DES increased cell proliferation and sprouting of endothelial cells, and VEGF expression transitioned from a vessel-surrounding pattern to a diffuse pattern. During later stages, angiogenesis was predominant, and VEGF expression decreased. In contrast to the early abundant expression of VEGF, endothelial expression of AQP-1 increased during later stages. Our data indicated a dynamic scenario of biological alterations in DES-treated pituitary tissue, in which VEGF and AQP-1 exert their functions at different stages of induction, and we provide novel insights into understanding oestrogen-related tumourigenesis in the anterior pituitary gland.