Role of vascular endothelial growth factor (VEGF) in the formation of vascular system for regulating the adenohyphysial function

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Anterior pituitary hormones are regulated by hypothalamic neurohormones, which are produced in the hypothalamic area and transported to the pars distalis via portal vessels. The hypophyseal portal system provides an important line for carrying hormonal information from the central nervous system to the pituitary. Vascular endothelial growth factor (VEGF) is known to have a mitogenic effect on endothelial cells and renders the endothelium more permeable.The present study using immunohistochemistry and FITC-conjugated to gelatin injection method showed a close relationship between hormone-producing cells and microvessels in hypothalamic-pituitary axis. The Northern blot analysis detected VEGF mRNA in the pars distalis, brain, lung and kidney with the lowest levels in the pars distalis. The in situ RT-PCR method clearly demonstrated the presence of VEGF mRNA-expressing cells in the rostral and ventral regions of the pars distalis at fetal 15.5 day. Expression levels decreased at fetal 18.5 day, but the positive cells were observed throughout the entire ventral region. On the other hand, the microvessels penetrated into the pars distalis at fetal 15.5 day and subsequently expanded into the entire lobe to form the secondary plexus. These results suggest that VEGF is involved in the vascularization of the pars distalis, but not in the formation of portal vessels, because the formation of portal vessels begins at fetal 13.5 day, before the appearance of VEGF in the rostral region of the pars distalis. The dual staining of in situ RT-PCR and immunohistochemistry indicates that some ACTH cells have the potential to produce VEGF. Similar finding was obtained in the bullfrog pituitary glands during metamorphosis. I also cloned cDNA fragments encoding VEGF of rainbow trout and bullfrog. Thus, these data provide fundamental clues in evolutionary aspect of the formation of the vasculalization of hypothalamic-pituitary axis.