Multiple measurements of gene expression in single, living cells enable molecular analysis of endocrine cell heterogeneity.
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Animals↗
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THE ENDOCRINE CELLS OF THE KIDNEY.
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Animals↗
Immunocytochemical study of intestinal endocrine cells in germ-free mice.
Morphological and functional modifications have been described in the gastrointestinal tract of germ-free rodents in comparison to their conventional counterparts. These differences have been related to the absence of normal flora, but peptides and biogenic amines may also be involved. Enteroglucagon-, peptide YY-, somatostatin-, serotonin-, neurotensin-, chole-cystokinin-, and secretin-producing cells were studied by immunocytochemistry in the ileum, cecum and colon of 10 germ-free, 10 conventional and 5 conventionalized CFW adult male mice. In the cecum and colon of germfree mice, enteroglucagon- and peptide YY-positive cells appeared enlarged, were globular in shape and strongly immunostained. Enlarged and strongly immunostained serotonin- and neurotensin-positive cells were also seen in some germ-free mice. Somatostatin-positive cells and all the endocrine cells of the ileum were similar in the 3 groups, and no cholecystokinin- or secretin-positive cells were observed. Our results are consistent with higher enteroglucagon and peptide YY production in germ-free mice that may be related to the lower cellular renewal rates and slower gastrointestinal transit reported in these animals. Locally produced biogenic amines and peptides may be important factors in the mediation of the effect of the intestinal flora on gastrointestinal structure and function and germ-free mice seem to be a good model for the study of the mechanisms involved.
APUD Cells↗
The responses of gut endocrine cells to physiological stimuli: a quantitative immunocytochemical study.
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Animals↗
An immunocytochemical study of endocrine cells in the gut of a stomachless teleost fish, grass carp, Cyprinidae.
Nineteen different antisera raised against mammalian hormones were used to identify the occurrence and distribution of endocrine cells in the gut of grass carp (Ctenopharyngodon idellus). Positive reactions were obtained in gut epithelium with antisera gastrin, glucagon, gastric inhibitory peptide, leucine enkephalin, substance P, and bovine pancreatic polypeptide. No immunoreactive product was formed using antisera against somatostatin, 5-hydroxytryptamine, insulin, avian pancreatic polypeptide, motilin, cholecystokinin, secretin, neurotensin, vasoactive intestinal polypeptide, bombesin, neuron-specific enolase, prochymosin, and pepsinogen. The exact distribution mapping of six kinds of immunoreactive endocrine cells throughout the gut of grass carp (C. idellus) is presented. The morphological characteristics of immunoreactive endocrine cells is described. Their distribution characteristics and possible modes of secretion and function are discussed. Finally, the possible relationship between the transplantation of these cells in the gastro-entero-pancreatic endocrine system is discussed.
Animals↗
Ultrastructural study of the endocrine cells of the gut of Testudo graeca (Chelonia).
The digestive tract of Testudo graeca (Chelonia) was investigated by means of electron microscopy using both conventional and immunocytochemical techniques. EC-, L-, D-, G-, B-, N- and EC-L-cells were detected. These cells share several common ultrastructural characteristics with the endocrine cells of mammals (i.e. clear cytoplasm, prominent Golgi apparatus, secretory granules etc.). EC and D1 cells have so far not been described in the esophagus of any animal species; in the present study these cells have been observed in the esophagus of T. graeca. Of special interest was the presence of B-cells in the intestine, suggesting that the migration of B-cells from the gut to the pancreas to constitute pancreatic islets is not concluded in T. graeca. The present study demonstrates that the gut endocrine system of T. graeca is a complex structure containing a large variety of endocrine cell types similar in morphology to those found in higher vertebrates.
Animals↗
Identification of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells.
Several proteins that are of importance for membrane trafficking in the nerve terminal have recently been characterized. We have used Western blot and immunohistochemistry to show that synaptotagmin, synaptobrevin/VAMP (vesicle-associated membrane protein), SNAP-25 (synaptosomal-associated protein of 25 kDa), and syntaxin proteins are present in cells of the islets of Langerhans in the endocrine pancreas. Synaptotagmin-like immunoreactivity (-LI) was localized to granules within the cytoplasm of a few endocrine cells located in the periphery of the islets, identified as somatostatin-containing cells, and in many nerve fibers within the islets. VAMP-LI was seen in granules of virtually all pancreatic islet cells and also in nerve fibers. SNAP-25-LI and syntaxin-LI were predominantly present in the plasma membrane of the endocrine cells, including insulin-producing beta cells. In situ hybridization, using isoform-specific oligonucleotide probes, detected VAMP-2, cellubrevin, SNAP-25, syntaxin 1A, 4, and 5, and munc-18 mRNAs in isolated pancreatic islets and in insulin-producing cells. The results show the presence of several synaptic proteins at protein and mRNA levels in pancreatic islet cells, suggesting that they may have specific roles in the molecular regulation of exocytosis also in insulin-secreting cells.
Animals↗
Distribution of peptide-containing neurons and endocrine cells in the rabbit gastrointestinal tract, with particular reference to the mucosa.
The distribution patterns of peptide-containing neurons and endocrine cells were mapped in sections of oesophagus, stomach, small intestine and large intestine of the rabbit, by use of standard immunohistochemical techniques. Whole mounts of separated layers of ileum were similarly examined. Antibodies raised against vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SOM), neuropeptide Y (NPY), enkephalins (ENK) and gastrin-releasing peptide (GRP) were used, and for each of these antisera distinct populations of immunoreactive (IR) nerve fibres were observed. Endocrine cells were labelled by the SP, SOM or NPY antisera in some regions. VIP-IR nerve fibres were common in each layer throughout the gastrointestinal tract. With the exception of the oesophagus, GRP-IR nerve fibres also occurred in each layer of the gastrointestinal tract; they formed a particularly rich network in the mucosa of the stomach and small intestine. Fewer nerve fibres containing NPY-IR or SOM-IR were seen in all areas. SOM-IR nerve fibres were very scarce in the circular and longitudinal muscle layers of each area and were absent from the gastric mucosa. The SP-IR innervation of the external musculature and ganglionated plexuses in most regions was rather extensive, whereas the mucosa was only very sparsely innervated. ENK-IR nerve fibres were extremely rare or absent from the mucosa of all areas, although immunoreactive nerve fibres were found in other layers. These studies illustrate the differences in distribution patterns of peptide-containing nerve fibres and endocrine cells along the gastrointestinal tract of the rabbit and also show that there are some marked differences in these patterns, in comparison with other mammalian species.
Animals↗
Immunocytochemical study of endocrine cells in pelvic ileal reservoirs.
The distribution and morphology of intestinal endocrine cells was investigated in the mucosa of pelvic ileal reservoirs using immunocytochemical methods. Endoscopic biopsies were obtained from 15 patients after the construction of a modified J-pouch. The mucosa of the reservoir showed a variable degree of colonic metaplasia in all cases. No relevant quantitative variations of gut endocrine cells were detected, as revealed by immunostaining for the general marker, chromogranin, compared with normal ileal mucosa. Immunostaining for different peptide-containing cells resulted in normal number and morphology of serotonin, enteroglucagon, peptide tyrosine-tyrosine, and somatostatin-containing cells. Neurotensin cells were less numerous than in normal mucosa. The role played by gastrointestinal hormones in the adaptive response of the intestine to pouch construction is, presently, unclear. Further studies involving measurements of fasting and meal-stimulated levels of gut hormones in pouch patients might clarify this aspect.
Adult↗
Immunocytochemical localization of cathepsins B and H in human pancreatic endocrine cells and insulinoma cells.
Cathepsins B and H are representative cysteine proteinases localized to lysosomes of a variety of mammalian cells. Previous studies indicated the presence of these enzymes also in secretory granules of endocrine cells. Therefore, the human endocrine pancreas and human insulinomas were investigated by light microscopical immunohistochemistry on serial semithin plastic sections immunostained sequentially for cathepsins B or H and pancreatic hormones. Out of the four established endocrine cell types, insulin (B-) and glucagon (A-) cells showed immunoreactivities for these cathepsins. Cathepsin B immunoreactivities showed a dot-like appearance in A- and B-cells and in insulinoma cells. Immunoreactivities for cathepsin H additionally were found in cell parts containing secretory granules of B-cells and insulinoma cells. By single and double immunoelectron microscopy the dot-like immunoreactivities for cathepsin B were identified as immunoreactive lysosomes of A- and B-cells and insulinoma cells. In addition, some of the secretory granules of A- and B-cells showed cathepsin B immunoreactivities. Cathepsin H immunoreactivities showed an other pattern: they were found regularly in the secretory granules of A- and B-cells and insulinoma cells, and in lysosomes of A-cells. These findings suggest that cathepsins B and H in lysosomes of A- and/or B-cells are involved in the degradation of lysosomal constituents. In secretory granules of these cells, these cysteine proteinases may participate in the processing of the corresponding hormones from their precursor proteins.
Adenoma, Islet Cell↗
Malignant pleural effusions due to adeno-endocrine-cell carcinoma of the appendix: a case report.
The cellular features of adeno-endocrine-cell carcinoma of appendiceal origin are presented. The pleural fluid contained metastatic predominantly atypical cells in linear cluster accompanied by numerous mesothelial cells. The cells had small round nuclei, with a slight tendency to molding; nucleoli were absent. The cytologic findings in Papanicolaou-stained smears of the pleural fluid suggested a metastatic small-cell carcinoma of the lung. Subsequently, adeno-endocrine-cell carcinoma of the appendix was demonstrated at autopsy. Reports of such occurrences are few; no study, to the best of our knowledge, has previously documented the cytologic diagnosis in pleural fluid.
Adenocarcinoma↗
Distribution and development of peptidergic nerves and gut endocrine cells in mice with congenital aganglionic colon, and their normal littermates.
Studies were made of the distribution of gut hormones and neuropeptides in the gastrointestinal tract of mice with hereditary aganglionic colon (s1/s1) and their normal littermates. Antisera to substance P, vasoactive intestinal polypeptide, and enkephalins demonstrated markedly diminished numbers of immunofluorescent nerve fibers in the aganglionic segment of colon; in contrast, in proximal colon and small intestine the distribution of peptidergic nerve fibers was essentially normal. Mucosal endocrine cells were demonstrated in the colon by antisera to substance P, somatostatin, glucagon, and cholecystokinin; in each case there were similar numbers of cells in s1/s1 and normal mice. Radioimmunoassays for vasoactive intestinal polypeptide and bombesin showed diminished concentrations of immunoreactive material in the aganglionic segment of colon of 16-17-day-old animals. However, assays for CCK--which is predominantly located in endocrine cells--showed similar concentrations of immunoreactive material throughout the gut of s1/s1 and normal mice. It was of interest that the concentrations of immunoreactive substance P were lower than normal not only in the aganglionic segment of colon, but also in proximal colon and distal small intestine, and that at all ages the development of substance P in the intestine was delayed in the s1/s1 mice. The results are consistent with the idea that the constriction of the aganglionic segment of colon develops as a consequence of lack of intrinsic inhibitory neurons, possibly those containing vasoactive intestinal polypeptide. The presence of an aganglionic segment is attributable to delayed migration of the neuroblasts from the neural crest. Thus the findings of normal populations of gut endocrine cells in the aganglionic segment is further support for the view that the embryologic origin of gut endocrine cells is different to that of gut neurons.
Animals↗
[Endocrine cells of the gastroduodenal area in duodenal ulcer].
A study has been carried out to substantiate the assumption that excessive proliferation of major gastroduodenal endocrine cells may be predetermined genetically. Hereditary predisposition to the hyperplasia of cells belonging to the APUD system may be inherited both through the male and female lines. Duodenal ulcers (DU) undoubtedly involves multifactorial inheritance. Acquired capacity for endocrine cell hyperplasia cannot be excluded in some of DU patients. The development of DU is, apparently, related to the formation of a pathological system, based on pathologic structure-linked neurohormonal relationships between the duodenum and peripheral and central nervous systems that enhance nerve impulses in the duodenal bulbar portion. A sudden "total" catecholamine release occurs at a certain stage and is followed by a change of production/utilization ratios of various hormones that weakens pathologic neurohormonal relationships, destroys the pathologic system and activates the healing process around the ulcer. The pathologic system, active in peptic ulcers, is doubtless counteracted by a system, whose activity must be determined by the number of endocrine cells with beta-endorphine-like and, perhaps, serotonin-like immunoreactivity. The antagonistic regulation principle is of great universal significance for general biology. It is essential for healing and chronization processes.
APUD Cells↗
[Ultrastructure of endocrine cells in the gastric fundal glands at different seasons of the year].
Endocrine cells of gastric glands of Citellus erythrogenus Brandt were studied during various seasons of the year by electron microscopy. ECL, EC, D and D1 cells having different structure of granules were detected. The slightly changed, weakly functioning cells as well as the cells of different alteration degree (up to destructing) were found in hibernating rodents. The presence of actively functioning EC-cells over this period confirms an opinion concerning the influence of peripheral serotonin on the hibernation mechanism. On the 3d--4th day of awakening pronounced activation of endocrine cells, their rejuvenation and normalization of cell ultrastructure, completed two weeks after awakening, were noted.
Animals↗
Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia.
Clinical and experimental evidence indicates that carcinoid tumours of the stomach fundic mucosa represent another example of hormone-dependent neoplasm, gastrin being the hormone involved in tumour induction. In this context hyperplasia of fundic endocrine cells associated with chronic atrophic gastritis (CAG) and hypergastrinaemia is regarded as the most frequent preneoplastic lesion. However, the cell type involved in this hyperplasia has not been clarified. To elucidate this problem fundic endocrine cells were characterized ultrastructurally in 9 patients from which endoscopic gastric biopsies were obtained. ECL cells were the most frequent cell type in 8 cases, in 4 of which they were more numerous than all other cell types taken together. D1 cells were the most frequent type in one case while they were inconspicuous in the other cases. P cells were found with a frequency in each case intermediate between that of ECL cells and that of D1 cells. These results indicate that fundic endocrine cell hyperplasia occurring in hypergastrinaemic CAG is in most cases cytologically similar to that found in other hypergastrinemic conditions, in which the gastrin-dependent ECL cells were already found to prevail. They also explain why fundic carcinoids arising in CAG are mostly composed of ECL cells. The relation between ECL, D1 and P cells, if any, remains obscure.
Adolescent↗
Immunocytochemical localization of cathepsin B in rat anterior pituitary endocrine cells, with special reference to its co-localization with renin and prorenin in gonadotrophs.
We examined by immunocytochemistry the localization of cathepsin B in endocrine cells of rat anterior pituitary lobe, using a monospecific antibody to cathepsin B. By light microscopy, granular immunodeposits for cathepsin B were detected in most endocrine cells of anterior pituitary lobe. Cells immunoreactive for luteinizing hormone (LH) were diffusely immunostained by anti-cathepsin B. By electron microscopy, immunogold particles for cathepsin B were localized in lysosomes of thyrotrophs, somatotrophs, and mammotrophs. In mammotrophs, immunogold particles for cathepsin B were also detected in crinophagic bodies. Double immunostaining co-localized immunogold particles for LH and cathepsin B in secretory granules of gonadotrophs. Immunocytochemistry was also applied to demonstrate localization of renin and prorenin in LH-producing gonadotrophs; immunogold particles for renin were co-localized with those for LH, cathepsin B, or prorenin in their secretory granules. Immunogold particles for prorenin were also co-localized with those for LH or cathepsin B in secretory granules, but prorenin-positive granules appeared less frequently than renin-positive granules. These results suggest that cathepsin B not only plays a role in the protein degradation in lysosomes of anterior pituitary endocrine cells but also participates in the activation of renin in gonadotrophs, as has been demonstrated in secretory granules of juxtaglomerular cells.
Animals↗
Pattern of gastric endocrine cells in microcarcinoidosis--an immunohistochemical study of 14 gastric biopsies.
A total of 14 gastric biopsy specimens from patients with microcarcinoidosis were analysed by immunohistochemical methods to evaluate the pattern of endocrine cell hyperplasia and dysplasia. All the patients had type A gastritis (autoimmune gastritis). Nonantral proliferations of gastric endocrine cells were classified according to Solcia et al. All 14 cases had hyperplasia and 13 (92.9%) of them, dysplasia of gastric endocrine cells; 9 (64.3%) of the 14 were found to have showed a coexisting invasive gastric carcinoid at the time of diagnosis of microcarcinoidosis. The patients with invasive carcinoids had higher degrees and more complex forms of endocrine dysplasia (precarcinoid lesions). The average size of the foci of the microcarcinoidosis in gastric biopsies was 0.14 +/- 0.09 cm in the patients without invasive carcinoid, as against to 0.5 +/- 0.24 cm in the group of patients with associated invasive carcinoid. Microcarcinoid gastric biopsies about 0.5 cm in size, are suggestive of adjacent invasive carcinoid. However, even frankly invasive ECL carcinoids seem to be clinically less dangerous than was thought until recently.
Adult↗
Endocrine cells in the gastric mucosa of elasmobranch fishes. An ultrastructural study.
The endocrine cells of gastric mucosa of two elasmobranch species were studied by light and electron microscopy. Five cell types were identified in the fundic mucosa, four of which are of "open type". All of them show pleomorphic granules of variable size, except those of the type V cell which are round in shape and of comparatively small diameter. Six different cell types are found in the pyloric mucosa, all of "open type" except for type XI cells which appear to be "closed". Pyloric types VIII, IX, X and XI cells show similar structural characteristics as fundus types I, V, II and IV respectively. Silver impregnation was also used at both light and electron microscopical levels. No functional classification or analogies with other vertebrate gastric endocrine cells were attempted as these would be too speculative on the basis of ultrastructural characteristics only.
Animals↗