This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O'Hare, M. M. T. Articles by Schwartz, T. W. Search for Related Content PubMed PubMed Citation Articles by O'Hare, M. M. T. Articles by Schwartz, T. W.

Expression and Precursor Processing of Neuropeptide Y in Human Pheochromocytoma and Neuroblastoma Tumors¹

Laboratory of Molecular Endocrinology, University Department of Clinical Chemistry, Rigshospitalet 6321, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

The expression of the potent vasoactive peptide neuropeptide Y (NPY) was studied in 16 clinically and/or histologically diagnosed human pheochromocytomas and 3 human neuroblastoma tumors. All tumors contained NPY in concentrations ranging from 21 pmol/g of tissue, similar to that found in normal adrenal tissue, to 91,000 pmol/g (median, 1,700 pmol/g). Three control tumors of Cushing's type did not contain NPY. An almost total proteolytic processing of pro-NPY to normal NPY was observed in the tumors (median, 93%; range, 72–100%). A positive correlation between the processing efficiency and the NPY content was also observed. The small amount of pro-NPY found in the tumors was characterized by "in vitro conversion" with endoproteinase Lys-C. In the tumor extracts, the majority of the NPY immunoreactivity, corresponding in size to the NPY standard, also behaved like synthetic NPY by high performance liquid chromatography and isoelectric focusing. As assessed by both its elution position in isoelectric focusing and its reaction with an antiserum specific for the COOH-terminal amidated sequence, the peptide produced by the tumors was found to be efficiently amidated, a modification which is essential for the biological activity of NPY. It is concluded that although only a subset of chromaffin cells express NPY, a very high number of pheochromocytomas and neuroblastomas produce correctly amidated and thus biologically active NPY in large amounts, and that this is of potential importance for tumor-related cardiovascular symptoms and for autocrine stimulation of tumor cells.

¹ This investigation was supported in part by the Danish Cancer Association and the Danish Medical Research Council. T. W. S. was the recipient of a Research Professorship in Molecular Endocrinology from the Danish Medical Research Council and the Weimann Foundation.

² To whom requests for reprints should be addressed.

Received 5/25/89. Revised 9/11/89. Accepted 9/21/89.

This article has been cited by other articles:

				A. Karagiannis, D. P Mikhailidis, V. G Athyros, and F. Harsoulis Pheochromocytoma: an update on genetics and management Endocr. Relat. Cancer, December 1, 2007; 14(4): 935 - 956. [Abstract] [Full Text] [PDF]

				S. Cleary, J. K Phillips, T.-T. Huynh, K. Pacak, A. G Elkahloun, J. Barb, R. A Worrell, D. S Goldstein, and G. Eisenhofer Neuropeptide Y expression in phaeochromocytomas: relative absence in tumours from patients with von Hippel-Lindau syndrome J. Endocrinol., May 1, 2007; 193(2): 225 - 233. [Abstract] [Full Text] [PDF]