Exp Clin Endocrinol Diabetes 2003; 111 - P4
DOI: 10.1055/s-2003-817546

Expression and role of VEGF receptors in pituitary adenomas

C Onofri 1, M Theodoropoulou 1, Y Grübler 1, M Losa 2, M Lange 3, W Stummer 4, GK Stalla 1, U Renner 1
  • 1Max-Planck-Institute of Psychiatry, Department of Endocrinology, Munich, Germany
  • 2Department of Neurosurgery of the Hospital San Raffaele, Milano, Italy
  • 3Klinikum Villingen-Schwenningen, Germany
  • 4Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany

Vascular endothelial growth factor (VEGF) is known to exert a highly specific mitogenic action on endothelial cells through two tyrosine kinase receptors: VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1/KDR) which are almost specifically expressed in endothelial cells. However, it has been shown that VEGF receptors may also be expressed by non-endothelial cells, especially by tumor cells. We have recently shown that pituitary adenoma cells produce variable amounts of VEGF and have now started to study the expression of VEGF receptors in normal human pituitary and pituitary adenomas by RT-PCR, in situ hybridisation and immunohistochemistry. Expression of VEGFR1 and VEGFR2 mRNA was found in normal pituitary and in the 49 adenomas (26 nonfunctioning, 9 somatotroph, 8 corticotroph and 6 lactotroph tumors) studied so far. The expression was variable and no correlation between VEGFR1 expression and tumor grade and vessels number was found. In normal pituitary, VEGFR1 immunoreactivity was observed to co-localize with ACTH-, FSH-, GH- and LH-secreting cells, but not in endothelial cells, suggesting that VEGF may affect function of endocrine cell types by paracrine mechanisms. In contrast, VEGFR2 immunoreactivity was detected only in the vascular formations, in both normal pituitary and pituitary adenomas. Immunohistochemical analysis for VEGFR2 in 33 pituitary adenomas (9 nonfunctioning, 7 somatotrophs, 6 corticotrophs and 11 lactotrophs) revealed immunoreactivity in the vascular formation of 18 tumors and we observed that somatotroph and corticotroph adenomas showed the highest number of cases with VEGFR2 immunoreactivity on vessels. However, we found no correlation between VEGFR2 expression and extent of vascularization. We have then observed that HP75, a human non-functioning pituitary adenoma cell line secreting gonadotropins, expresses both VEGFR-1 and –2 mRNA and human VEGF165 is able to stimulate cells proliferation in a dose-dependent manner. This finding could suggest again a possible paracrine/autocrine action of VEGF on endocrine and tumor cells.