title: Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro.
abstract: Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investigated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alpha T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive (27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in the case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% by dexamethasone. TtT/GF cells were the most responsive to the different stimuli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and alpha T3-1 cells, basal VEGF levels where not enhanced with any of the stimuli tested. The majority of the human adenomas tested (92%) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta-estradiol, respectively. In conclusion, pituitary tumor cells are capable of producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocorticoids may have anti-angiogenic properties and therefore therapeutic relevance for the treatment of pituitary adenomas.
authors.affiliation: Max Planck Institute of Psychiatry, Department of Endocrinology, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lohrer
authors.forename: J
authors.initials: J
authors.lastname: Gloddek
authors.forename: U
authors.initials: U
authors.lastname: Hopfner
authors.forename: M
authors.initials: M
authors.lastname: Losa
authors.forename: E
authors.initials: E
authors.lastname: Uhl
authors.forename: U
authors.initials: U
authors.lastname: Pagotto
authors.forename: G K
authors.initials: GK
authors.lastname: Stalla
authors.forename: U
authors.initials: U
authors.lastname: Renner
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D012377:Rodentia; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: C495401:ADCYAP1 protein, human; C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004958:Estradiol; D013004:Somatostatin; D003907:Dexamethasone