Pituitary adenylate cyclase-activating polypeptide, interleukin-6 and glucocorticoids regulate the release of vascular endothelial growth factor in pituitary folliculostellate cells

There is increasing evidence that hormones play an important role in the co ntrol of endothelial cell function and growth by regulating the production of vascular endothelial growth factor (VEGF). VEGF regulates vascular perme ability and represents the most powerful growth factor for endothelial cell s. In the normal anterior pituitary, VEGF has been detected only in follicu lostellate (FS) cells. In the present study, the regulation of the release of VEGF from FS-like mouse TtT/GF cells, and from FS cells of rat pituitary monolayer cell cultures was investigated using a specific VEGF ELISA. Basa l release of VEGF was demonstrated in cultures of both TtT/GF cells and rat pituitary cells. Interestingly, the VEGF secretion was stimulated by both forms of pituitary adenylate cyclase-activating polypeptide (PACAP-38 and P ACAP-27), indicating that this hypothalamic peptide regulates endothelial c ell function and growth within the pituitary. VEGF secretion was also stimu lated by interleukin-6 (IL-6) whereas basal, IL-6- and PACAP-stimulated sec retion was inhibited by the synthetic glucocorticoid dexamethasone. The inh ibitory action of dexamethasone was reversed by the glucocorticoid receptor antagonist RU486, suggesting that in FS cells functional glucocorticoid re ceptors mediate the inhibitory action of glucocorticoids on the VEGF secret ion. The endocrine and auto-/paracrine control of VEGF production in pituit ary FS cells by PACAP, IL-6 and glucocorticoids may play an important role both in angiogenesis and vascular permeability regulation within the pituit ary under physiological and pathophysiological conditions.