Expression of neurotensin in endocrine tumors.

Abstract

Endocrine tumors are useful sources for determining the synthesis and metabolism of secreted regulatory peptides. The present study was performed to compare the synthesis and metabolism of neurotensin (NT) in normal subjects and four patients with NT-producing tumors. NT mRNA was measured and characterized using oligonucleotide probes and Northern blots, while NT-like peptides were quantitated by RIA with region-specific antisera and high pressure liquid chromatography. Northern blot analysis of mRNA isolated from normal human ileum revealed two species of mRNA hybridizing to a heterologous canine oligonucleotide probe; the apparent sizes of the mRNA were 1.4 and 1.0 kilobases. An identical pattern was found in a pancreatic endocrine tumor, a prostatic adenocarcinoma, and a fibrolamellar hepatoma. The ratio of mRNA to peptide varied between the different tissues. For instance, the hepatoma was the richest source of NT mRNA, but the prostatic tumor contained the highest peptide concentration. Measurements with region-specific antisera showed that N-terminal immunoreactive fragments were more abundant than C-terminal fragments in pancreatic, prostatic, and carcinoid tumors (N/C-teminal ratios, 4.0, 1.6, and 5.0) and in equal concentrations in normal ileum. Reverse phase high pressure liquid chromatography revealed the presence of intact NT in addition to a variable number of smaller N-terminal peptides, presumed to be metabolites. In contrast the hepatoma contained a 5-fold excess of C-terminal immunoreactivity. The excess C-terminal immunoreactivity was also present in the circulation of this patient. The chromatographic properties, immunoreactivity, and unusual stability of the C-terminal fragment found in the hepatoma patient suggest that it is a substance distinct from NT itself and is released specifically by the fibrolamellar hepatoma.