Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro

Penny Lohrer, Jutta Gloddek, Ursula Hopfner, Marco Losa, Eberhard Uhl, Uberto Pagotto, Günter K. Stalla, Ulrich Renner

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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 αT3-1 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-α (TGF-α), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and αT3-1 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-α, PACAP-38, and 17β-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.

Original languageEnglish
Pages (from-to)95-105
Number of pages11
JournalNeuroendocrinology
Volume74
Issue number2
DOIs
Publication statusPublished - 2001

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Keywords

  • αT3 cell line
  • Adrenal steroids
  • Angiogenesis
  • AtT20 cell line
  • GH3 cell line
  • Growth factors
  • Human
  • Interleukins
  • Pituitary adenylate cyclase-activating polypeptide
  • Pituitary cell lines
  • Pituitary tumors
  • Somatostatin
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this

Lohrer, P., Gloddek, J., Hopfner, U., Losa, M., Uhl, E., Pagotto, U., Stalla, G. K., & Renner, U. (2001). Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro. Neuroendocrinology, 74(2), 95-105. https://doi.org/10.1159/000054675