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Journal of Histochemistry and Cytochemistry, Vol. 50, 533-540, April 2002, Copyright © 2002, The Histochemical Society, Inc.

ARTICLE

Expression and Distribution of Vascular Endothelial Growth Factor Receptor Flk-1 in the Rat Pituitary

Sergio Vidala,c, Ricardo V. Lloydb, Lucas Moyaa, Bernd W. Scheithauerb, and Kalman Kovacsc
a Department of Anatomy, Laboratory of Histology, University of Santiago de Compostela Lugo, Lugo, Spain
b Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
c Department of Laboratory Medicine, St Michael's Hospital, Toronto, Ontario, Canada

Correspondence to: Sergio Vidal, Dept. of Anatomy, Laboratory of Histology, U. of Santiago de Compostela, Campus Univeritario de Lugo, 27002 Lugo, Spain. E-mail: svidal@lugo.usc.es

Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the specific receptors Flk-1 and Flt-1. To help further define the possible role of VEGF in the control of pituitary cell function, we examined Flk-1 expression in normal rat pituitaries and in GH3 cells. Flk-1 expression was studied by immunohistochemistry, in situ hybridization, and double-labeling immunofluorescence combined with confocal laser microscopy. In normal rat pituitaries, Flk-1-immunoreactive cells appeared widely distributed only in the anterior lobe and were not detected in the intermediate or posterior lobe. Apart from the adenohypophysial cells, Flk-1 immunopositivity was also evident in endothelial cells of many capillaries distributed throughout the gland. Immunohistochemistry also showed that majority of GH3 cells expressed Flk-1 protein. In situ hybridization showed conclusive staining with the antisense probe and confirmed the immunohistochemical results. The double immunofluorescence method revealed Flk-1 expression in all types of hormone-producing adenohypophysial cells but not in folliculostellate cells. The percentage of immunopositive cells varied among the various cell types. The present study demonstrates that pituitary cells are not only sources of VEGF but also targets of this multifunctional substance, supporting the concept that VEGF functions as an autocrine/paracrine factor in the pituitary. (J Histochem Cytochem 50:533–540, 2002)

Key Words: GH3 cell line, rat, immunocytochemistry, pituitary, in situ hybridization, confocal microscopy, VEGF, VEGF receptors, Flk-1 receptor


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