Vascular endothelial growth factor in the rat pituitary: differential distribution and regulation by estrogen

Vascular endothelial growth factor (VEGF), an endothelial cell mitogen and permeability factor, participates in tumor angiogenesis, but less is known about its regulation or function in normal vascular homeostasis. In the ute rus, which undergoes cyclic changes in its vasculature, VEGF is induced by estrogen. Since the pituitary gland contains highly permeable capillaries a nd is estrogen-responsive, our objectives were to localize VEGF expression within the pituitary and to determine whether it is regulated by estrogen i n both the pituitary and the somatolactotrope cell line, GH(3). Ovariectomized rats were injected with estradiol, and pituitaries and uteri were subjected to in situ hybridization or quantitative reverse transcript ion-polymerase chain reaction (RT-PCR). VEGF expression was strong and punc tate in the neural lobe, weaker and diffuse in the anterior lobe and undete ctable in the intermediate lobe. Two VEGF isoforms, 164 and 120, were detec ted in all tissues. In the posterior pituitary, VEGF expression was 3-to 6- fold higher than in the anterior pituitary or uterus and was unaltered by e strogen. In contrast, anterior pituitary VEGF was induced by estrogen withi n 1 h, peaked at 3 h, and returned to basal levels by 24 h. Similar dynamic s, albeit 10-fold higher, were seen in the uterus. Translated VEGF proteins were detected by Western blot in both the anterior pituitary and uterus. G H(3) cells also showed a dose- and time-dependent induction of VEGF express ion by estrogen. In conclusion: (1) VEGF expression is higher in the neural lobe than in the anterior lobe: and is undetectable in the intermediate lobe, (2) the expre ssion of VEGF164 and VEGF120 is rapidly upregulated by estrogen in the ante rior pituitary but is unchanged in the posterior pituitary, and (3) the pit uitary lactotrope cell Line, GH(3), also increases VEGF expression in respo nse to estradiol.