Ghrelin-producing endocrine tumors of the stomach and intestine

Ghrelin is a novel gastrointestinal hormone produced by about 20% of the ra t and human gastric neuroendocrine cell population, which possesses strong GH-releasing activity, but also plays other central and peripheral roles, i ncluding influence on food intake, gastric motility, and acid secretion. Th e aim of the present study was to determine whether gastrointestinal endocr ine hyperplastic and neoplastic lesions produce ghrelin, at both protein (i mmunohistochemistry) and mRNA (in situ hybridization and/or RT-PCR) levels, and express the GH secretagogue receptor mRNA by RT-PCR. Sixteen gastric a nd 20 intestinal carcinoids as well as normal gastrointestinal mucosa and a trophic gastritis-associated neuroendocrine cell hyperplasia were studied. The majority (12 of 16, 75%) of gastric carcinoids and only 5 of 18 (27%) o f intestinal endocrine tumors were immunoreactive for ghrelin. In situ hybr idization confirmed the immunohistochemical data, but also showed ghrelin m RNA in 1 gastric and 8 intestinal additional tumors. RT-PCR showed ghrelin mRNA in 14 of 14 cases, indicating a low level of ghrelin gene expression i n all gastrointestinal endocrine tumors tested. Gastric neuroendocrine hype rplastic cells were also strongly positive for ghrelin. GH secretagogue rec eptor mRNA was absent in 3 gastric, but present in 7 of 11 intestinal carci noids studied by RT-PCM These findings demonstrate that most gastric carcin oids (and related neuroendocrine cell hyperplasias) and some intestinal car cinoids produce ghrelin. These hyperplastic/neoplastic conditions could rep resent the clinical model to clarify the existence and impact of ghrelin hy persecretion on endocrine and nonendocrine functions.