gastrins and Rodent-Diseases

Topics: Animals; Calcitonin; Calcium; Dog Diseases; Dogs; Gastrins; Hormones; Hypercalcemia; Hypocalcemia; Mammals; Parathyroid Glands; Perfusion; Phosphates; Rats; Rodent Diseases; Species Specificity; Stimulation, Chemical; Swine; Swine Diseases; Thyroid Gland

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas. The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and for gene expression by northern blot analysis. Among eight female cotton rats, three had an irregularly thickened oxyntic mucosa, increased stomach weight and a high serum gastrin level. Histopathological examination showed adenomatous hyperplasia of the thickened oxyntic mucosa with areas of an invasive neoplastic tumour. Immunohistochemistry, using the general neuroendocrine cell marker chromogranin A (CgA) and the specific ECL cell marker histidine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia. Parietal cells were not found in the tumour tissue. Parietal cell density was only slightly reduced in the surrounding oxyntic mucosa. The antral mucosa was histopathologically normal with a normal number of gastrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells did not show any differences in the antral and oxyntic mucosa between rats with pathological and normal oxyntic mucosa. Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H(+)/K(+) ATPase mRNA was similar in the oxyntic mucosa of those with thickened and normal oxyntic mucosa. Gastrin mRNA in the antral mucosa was high in animals with thickened oxyntic mucosa. Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thickened oxyntic mucosa. We conclude that the spontaneous gastric carcinoma occurring in female cotton rats is an ECLoma developing secondary to hypergastrinaemia due to reduced intragastric pH. The mechanism for reduced acidity is not known, but is not gastric atrophy.

Topics: Animals; Blotting, Northern; Chromogranin A; Chromogranins; Enterochromaffin Cells; Female; Gastric Acidity Determination; Gastrins; H(+)-K(+)-Exchanging ATPase; Histidine Decarboxylase; Immunohistochemistry; Parietal Cells, Gastric; RNA, Messenger; Rodent Diseases; Sigmodontinae; Somatostatin; Stomach Neoplasms

Female inbred cotton rats develop adenocarcinomas in the oxyntic mucosa. Since a female preponderance is typical for enterochromaffin-like (ECL) cell tumors, we examined such tumors for ECL cells. Gastrin plays a decisive role in ECL cell tumorigenesis, so blood gastrin concentration and gastric mucosal pH were measured.. The stomachs from six female cotton rats (6 to 8 months old) were studied histologically, and at euthanasia, gastric mucosal pH was determined. Euthanasia was performed on 15 other female cotton rats of similar age for determination of blood gastrin values by radioimmunoassay (RIA) and gastric mucosal pH. Rats were classified macroscopically to have normal or thick oxyntic mucosa, with or without tumor.. Among the six cotton rats studied histologically, two 6-month-old rats had normal and two others had thick gastric mucosa, whereas two 8-month-old rats had thick mucosa with tumors. The ECL cells were markedly hyperplastic in all rats with thick mucosa, and ECL cells were found in the neoplastic parenchyma. All cotton rats with normal-appearing gastric mucosa had pH <2.5, whereas 14 rats with thick mucosa had pH >3.1 and hypergastrinemia.. Gastrin may play a major role in ECL cell hyperplasia and, perhaps, in adenocarcinoma genesis.

Topics: Adenocarcinoma; Animals; Chromogranin A; Chromogranins; Enterochromaffin Cells; Female; Gastrins; Histidine Decarboxylase; Hydrogen-Ion Concentration; Hyperplasia; Immunoenzyme Techniques; Male; Radioimmunoassay; Rats; Rodent Diseases; Sigmodontinae; Stomach Neoplasms; Synaptophysin

Endocrine cells in the normal glandular stomach and gastric carcinoids of mastomys were observed by electron microscopy and at least five types of endocrine cells, EC, G, D-like, R (round-granule) and ECL cells were identified. Of these, four types excepting G cells were recognized in the fundic mucosa. Characteristic in mastomys was a scarcity of endocrine cells in the fundic mucosa, where ECL and R cells were predominant types. Silver impregnation methods including SEVIER-MUNGER's argyrophil reaction of our own modifications were applied to tissue sections and the endocrine cells were examined by electron microscopy. Only EC cells revealed argentaffin granules under the light and electron microscope. R, ECL and some of the G cells were non-argentaffin and argyrophil in reaction and D-like cells and the rest of the G cells failed to show even an argyrophil reaction. Granules of mastomys carcinoid cells, as noted in the previous reports, were non-argentaffin but faintly argyrophil. Mastomys gastric carcinoids were studied by the same method, with special reference to the parent cells of this particular neoplasia. Noteworthily, mastomys gastric carcinoids arise mostly from the fundus, the area where R and ECL cells mainly occur in normal animals. The neoplasms are composed of cells containing granules resembling partly those of R cells and partly those of ECL cells. ECL cells and neoplastic cells in the present investigation have a similar reactivity to SEVIER-MUNGER's method. Considering the generally accepted fact that neoplastic cells may not fully duplicate their parent cells in cytological features, it seems reasonable to presume that R and/or ECL cells might be the parent cells of the mastomys gastric carcinoids. In connection with this assumption histamine has been demonstrated to be produced both in mastomys carcinoid cells and normal ECL cells.

Topics: Animals; Carcinoid Tumor; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Golgi Apparatus; Mice; Rodent Diseases; Stomach Neoplasms