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Exp Clin Endocrinol Diabetes 2004; 112(1): 18-23
DOI: 10.1055/s-2004-815722
Article

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

C. Onofri[*] 1 , A. Carbia Nagashima[*] 2 , L. Schaaf 1 , M. Feirer 1 , P. Lohrer 1 , W. Stummer 3 , S. Berner 4 , A. Chervin 4 , V. Goldberg 5 , G. K. Stalla 1 , U. Renner 1 , E. Arzt 2
  • 1Max Planck Institute of Psychiatry, Department of Endocrinology, Munich, Germany,
  • 2Laboratorio de Fisiologia y Biologia Molecular, Department Fisiologia y Biologia Molecular, FCEN - Universidad de Buenos Aires and IFIBYNE-CONICET, Buenos Aires, Argentina
  • 3Department of Neurosurgery of the University of Munich, Munich, Germany
  • 4Hospital Santa Lucia, Buenos Aires, Argentina
  • 5Instituto de Investigaciones Medicas, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Further Information

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

References

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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