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DOI: 10.1055/s-2004-815722
J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York
Estradiol Stimulates Vascular Endothelial Growth Factor and Interleukin-6 in Human Lactotroph and Lactosomatotroph Pituitary Adenomas
Publication History
Received: January 27, 2003
First decision: April 14, 2003
Accepted: June 4, 2003
Publication Date:
03 February 2004 (online)
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Abstract
Estrogens are considered to be critically involved in lactotroph and lactosomatotroph pituitary tumor development. In addition to direct effects, estradiol-induced tumor formation may involve alterations in growth factor and cytokine production. We have studied whether estradiol stimulates the production of the angiogenic vascular endothelial growth factor and the potential tumor progression factor interleukin-6 in 5 lactotroph (LA) and 5 lactosomatotroph (LSA) human pituitary adenoma cell cultures. All tumors secreted heterogenous basal amounts of VEGF (18.0 ± 1.4 to 425 ± 26 pg/ml per 24 h) and IL-6 (18.1 ± 1.5 to 604 ± 17 pg/ml per 24 h). Estradiol (100 nM) significantly enhanced VEGF release in all LA and LSA cell cultures (47 to 168 % above basal). IL-6 secretion was stimulated in 3 out of 5 LA and in all LSA cell cultures (31 to 287 % above basal). In cell cultures obtained from tumors from which sufficient cells could be isolated, a dose-dependent effect of estradiol (1 to 100 nM) on VEGF and IL-6 production was observed. Stimulation of IL-6 and/or VEGF secretion by estradiol in the majority of human lactotroph and lactosomatotroph adenoma cell cultures studied, suggests that estrogens may contribute to adenoma expansion through the stimulation of these auto-/paracrine-acting adenoma progression factors.
Key words
Lactotroph/lactosomatotroph adenomas - estrogens - vascular endothelial growth factor - interleukin-6
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1 C. Onofri and A. Carbia Nagashima contributed equally to this work.
Ph.D. Ulrich Renner
Department of Endocrinology · Max Planck Institute of Psychiatry
Kraepelinstraße 10
80804 Munich
Germany
Phone: + 49(0)8930622349
Fax: + 49 (0) 89 30 62 26 05
Email: renner@mpipsykl.mpg.de