Endocrine cells in non-endocrine tumours.
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Endocrine Glands↗
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Cytokines and the endocrine system. II. Roles in substrate metabolism, modulation of thyroidal and pancreatic endocrine cell functions and autoimmune endocrine diseases.
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Animals↗
[Determination of autoantibodies to pancreatic beta-cells, non-islet endocrine cells and fibroblasts in patients with newly detected diabetes mellitus].
The clinical onset of insulin-dependent diabetes (IDD) is characterized by the onset of circulation of autoantibodies to beta-cells. Thirty-three newly detected IDD patients and 14 newly detected patients with noninsulin-dependent diabetes mellitus were examined for autoantibodies to antigen P 64-69, to surface antigen of islet cells, to thyrocyte microsomal fraction, thyroglobulin, hypophysis, fibroblasts; the levels of circulating immune complexes were measured as well. IDD debut was found associated with the appearance of antibodies to pancreatic islet cells, thyroid, thyroglobulin, hypophysis, fibroblasts, this indicating a polyclonal activation of the immunity system. A relationship was revealed between antifibroblast antibody and anti-islet-cell antibody. Antihypophyseal antibodies were detected in 43% of patients with noninsulin dependent diabetes. Nine per cent of IDD patients and 24% of patients with noninsulin dependent condition were negative in the tests.
Adolescent↗
Ontogeny of the endocrine cells of the intestine and rectum of sea bass (Dicentrarchus labrax L.): an ultrastructural study.
Several endocrine cell types were ultrastructurally characterized during the differentiation of the intestine and rectum of sea bass (Dicentrarchus labrax L.) larvae. Only one cell type (type I) was found in the posterior region of the undifferentiated gut of 5-day-old larvae (phase I). Types V and VI were found in both the intestine and rectum, types II, III and IV in the intestine, and types VII and VIII in the rectum of 9- and 12-day-old larvae (phase II), the rectum alone showing signs of functional differentiation. In phase III larvae, in which both the intestine and rectum were differentiated, types IX, X, XI, XII, XIII, XIV and XV were found in the intestine, only types X, XI and XII being seen in the rectum. Besides these, a new cell type, XVI, was observed in the intestine of 55- and 60-day-old larvae (phase IV), in which the digestive tract was completely differentiated. The endocrine cells appearing in phases I and II showed very scarce secretory granules and the ultrastructural features of undifferentiated cells. Some endocrine cell types in the earliest developmental stages were related to some of those found later. A maturational process of the endocrine cell types paralleled the differentiation of the intestine and rectum, with an apparent increase in the number of secretory granules accompanying organelle development.
Age Factors↗
[Immunomorphological characteristics of mucosal and endocrine cells of the colon in patients with chronic ulcerative colitis].
Morphological methods were used for the study of epithelial-stromal relations, free cells, lymphocyte population and endocrine cells of the colon during the stage of remission andexacerbation in patients with nonspecific ulcerative colitis (NUC). An increase of the total population of endocrine cells (with domination of serotonin-containing cells) in all altered parts of the colon was in chronic NUC. Disturbance of cooperation between the free stromal cells and epithelial components, correlation between population of T and B lymphocytes, increased number of CD8+ cells were seen in NUC exacerbation this being the basis of chronization and progression of this disease.
Adult↗
Hamster pulmonary endocrine cells with neural cell adhesion molecule (NCAM) immunostaining.
Pulmonary endocrine cells of Syrian golden hamster were stained for neural cell adhesion molecule (NCAM) with indirect fluorescent immunostaining and observed with a confocal laser scanning microscope equipped with an argon laser. Sections 100 microns thick of hamster lung fixed with phosphate-buffered 4% paraformaldehyde were prepared. The sections were incubated with rat monoclonal antibody against NCAM, followed by fluorescence-labeled antibody against rat immunoglobulin. Some were doubly immunostained for NCAM and one of the following endocrine markers: neuron-specific enolase, calcitonin gene-related peptide and serotonin. Expression of NCAM in the hamster airway epithelium was seen in cell nests resembling neuroepithelial bodies (NEBs). NCAM immunostaining was positive at the lateral cell borders between the cells composing the nest, but negative at the border with the adjacent, presumably non-endocrine cells. Double immunostaining confirmed that the grouped cells with NCAM immunoreactivity were of an endocrine nature, but that single endocrine cells did not show NCAM immunoreactivity. An electron microscopic study with NCAM immunostaining confirmed the light microscopic study. These suggest that NCAM expression could be important for the morphogenesis of NEBs. A confocal laser microscope was used to make three-dimensional images of NEBs after NCAM immunostaining and the spatial interaction between NEBs and the surrounding microenvironment was studied.
Animals↗
Ontogeny of endocrine cells in porcine gut and pancreas. An immunocytochemical study.
A number of peptide hormones and hormone candidates were studied by immunocytochemistry with respect to their appearance and distribution in the developing porcine gastroenteropancreatic region. The hormones of the pancreatic islets were the first to appear. At 4 weeks' gestation (the earliest stage studied), glucagon, insulin, and somatostatin cells occurred in the dorsal pancreatic primordium, whereas pancreatic polypeptide cells occurred in the ventral primordium. At this stage, the pancreatic primordia were made up of strands of endocrine cells, and no ducts or acini were seen. Subsequently, the endocrine cells were separated by the growing exocrine parenchyma; at still later stages, they aggregated in small nests. Not until birth did they form mantle islets with insulin cells in the central core and the other endocrine cell types on the outside. Gastrin cells appeared in the stomach at the 4-wk stage; somatostatin cells appeared about 1 wk later. In the intestines, these two cell types appeared at the 6-wk stage. Cells displaying glucagon immunoreactivity were the first endocrine cells to appear in the intestine. They occurred in the upper small intestine at the 4-wk stage; they later disappeared from this location but appeared instead in the lower small intestine and colon where they remained. Secretin, cholecystokinin, motilin, gastric inhibitory peptide, and neurotensin cells all appeared at the 6-8-wk stage, and were restricted to the small intestine throughout development. Enkephalin immunoreactive cells appeared late during ontogeny (at the 13-15-wk stage) in both the gut and pancreas. Still later (15-17-wk stage), dense accumulations of endocrine cells (Segi's cap) were occasionally observed on the top of villi in the upper small intestine; these accumulations consisted mainly of somatostatin, cholecystokinin, and gastric inhibitory peptide cells. In view of the early appearance of many gastroenteropancreatic endocrine cell types in fetal life, a functional significance of gastroenteropancreatic hormones in the early development of gut and pancreas is likely.
Adrenocorticotropic Hormone↗
Co-localization of Trk neurotrophin receptors and regulatory peptides in the endocrine cells of the teleostean stomach.
Recently it has been observed that a subpopulation of gut endocrine cells in vertebrates express Trk-like proteins, suggesting that neurotrophins could regulate the synthesis and storage of amines and peptides of these cells. Nevertheless, the peptides and amines present in the endocrine cells that express Trks have not been characterized. In this study we used immunohistochemistry to investigate the occurrence of Trk-like proteins (TrkA-like, TrkB-like and TrkC-like) and the possible co-localization of these with peptides and/or biogenic amines in the endocrine cells of the stomach of three teleost (bass, gilt-head and scorpionfish). No TrkA-like immunoreactivity (IR) was detected in the stomach of these species, whereas TrkB-like IR and TrkC-like IR were observed in numerous cells of the gastric epithelium. TrkB-like immunoreactive cells were present in all three species examined, and were particularly abundant in the blind sac. Conversely, TrkC-like immunoreactive cells were found only in the bass stomach, apparently co-localized with TrkB-like IR. TrkB-like IR was found co-localized with somatostatin IR in scorpionfish, and with somatostatin and CGRP IR in gilt-head and bass. Gastric endocrine cells expressing 5-HT, glucagon, insulin, met-, leu-enkephalin, substance P, PYY, VIP, CCK, NPY, bombesin and motilin were unreactive for Trk-like proteins. The present results provide direct evidence for the occurrence of Trk-like neurotrophin receptor proteins in a subpopulation of the teleostean gastric endocrine cells and suggest that neurotrophins could regulate, as in neurons, the expression of some neuropeptides such as somatostatin and CGRP.
Animals↗
Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach.
There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine markers NSE and PGP 9.5 revealed a proliferation of endocrine cells in the epithelium and isolated clumps of endocrine cells in the lamina propria. The clumps were composed of two cell types, either small or large. Some of these endocrine cells showed gastrin, 5HT, VIP and substance P immunoreactivity of varying intensity. Ultrastructurally nine morphologically distinct types of granules were found some of which correlated with the immunohistochemistry. Some separate islands were composed solely of endocrine cells while others had a definite neural component, suggesting that the former arise from 'budding off' of enteroendocrine cells and the latter originate from the neuroendocrine cells of the lamina propria plexus. Thus there may be a dual origin of carcinoid tumours. Carcinoid tumours associated with pernicious anaemia tend to be multifocal and are infrequent. Less than 50 such cases have hitherto been reported. Our findings of endocrine cells proliferations in seven cases of pernicious anaemia indicate that this may be an adaptive change that occurs frequently and provides the basis on which carcinoids, less frequently, develop.
Adult↗
The endocrine cells of the digestive system: amines, peptides, and modes of action.
The endocrine cells of the digestive system (entero-endocrine cells of gastro-intestinal epithelia and Langerhans' islets of the pancreas) and the chemical messengers produced by them constitute a complicated and complex system. The physiological function of this system is the regulation of all processes related to digestion and resorption, and to homeostasis of carbohydrate metabolism. Using morphological and histochemical features of this cellular community, the present review deals with amines and amine metabolism, polypeptides and their immunohistochemical identification, and with the modes of action of enteric and pancreatic hormones. Special attention is paid to the significance of amine precursor uptake and decarboxylation (APUD), to immunohistochemical methodology and the interpretation of immunohistochemical findings, and to local regulatory mechanisms, especially paracrinia. Finally, unifying concepts for the integration of these cells and similar endocrine cells of other organs into a common system are considered.
APUD Cells↗
[A biliary endocrine cell carcinoma: a report of two cases].
An endocrine cell carcinoma is a carcinoid tumor that has an especially malignant prognosis. We herein report on 2 cases of a biliary endocrine cell carcinoma. Case 1 involved a 68 year old man manifesting a fever, jaundice, hepatomegaly and a ballooned gallbladder. After decreasing the jaundice by PTCD, an exploratory abdominal operation was performed. As a tumor was found at the papilla of Vater, a pancreaticoduodenectomy was done. Case 2 involved a 72 year old woman who was diagnosed as having a gallbladder tumor and cholelithiasis. She was given a cholecystectomy and a choledocholithotomy. These 2 cases had hepatic metastasis within a year and subsequently died. Procedurally, an endocrine cell carcinoma should be treated separately from classical carcinoid tumors.
Aged↗
Appearance of immunoreactive endocrine cells during the development of the rat pancreas, with special reference to polypeptide-secreting cells.
The chronological appearance of PP cells in fetal pancreatic islets was studied using specific anti-PP serum and the direct peroxidase method. The presence of A and B cells was also studied, using the same immunocytochemical technique, as a reference pattern related to data previously reported. Our data confirm that the A cell is the earliest endocrine cell type, appearing on the 12th day of gestation, followed by B cells (14th day) and later on by PP cells (19th day). Primitive islets were identified in the pancreas after the 15th day. However, the spatial cell disposition observed in the adult islet was only recognized at the 20th day of gestation. The data reported provide the necessary information to establish the complete chronology in the rat fetus. Consequently, the development of pancreatic islets in the rat fetus could be employed as a useful model to study the existence of factors that control the sequential appearance of endocrine cells and the possible changes occurring in the islets of animals with genetic diabetes during the fetal period.
Animals↗
The distribution of endocrine cells along the mouse small intestine. Bombesin and somatostatin producing cells.
The topographical distribution and incidence of endocrine cells in the crypt and villus epithelium and along the length of the mouse intestine was studied. Cells containing somatostatin and bombesin like reactivity were stained by immunocytochemical techniques using polyclonal antiserum. Most of the somatostatin cells were found in the duodenum, jejunum and ileum, and these cells were generally more frequent on the villus compared to the crypts. This may indicate that the somatostatin cells develop late in the endocrine cell lineage. Bombesin like cells were rare in occurrence, and were only present in measureable numbers in the ileum, where they were observed in the crypt and villi. The application of ELISA assays to determine the specificity of the antisera for these peptides is also discussed.
Animals↗
Endocrine cells in colorectal carcinomas. Immunohistochemical study.
Immunostaining for chromogranin A, serotonin, glucagon and somatostatin revealed the presence of endocrine cells in 20 (35.1%) out of 57 randomly selected colorectal carcinomas. Expression of a general "neuroendocrine" marker, chromogranin A was detected in 18 tumours, whereas in the remaining two carcinomas positive reactivity with glucagon only was seen. Serotonin was expressed in 9 carcinomas, glucagon in 5 and somatostatin in 4 carcinomas. In 3 tumours coexpression of active products was found: in one--serotonin and glucagon, in another--serotonin and somatostatin, and in the last one--serotonin, glucagon and somatostatin. In 6 carcinomas expressing chromogranin A there was no expression of active products. Twelve carcinomas were assigned to a group with a small number of endocrine cells (up to 50/cm2 of tumour cross sectional area), 6 to a group with an intermediate number of endocrine cells (over 50 to 500/cm2) and 2 to a group with a large number of endocrine cells (over 500/cm2). The endocrine cells were significantly more frequent in less advanced and better differentiated carcinomas and in neoplasms with abundant mucin production. The cells were an integral part of glandular structures of the carcinoma, which argues in favour of a unitarian theory, i.e. common, endodermal origin of endocrine cells and other cellular elements of intestinal epithelium.
Adenocarcinoma↗
[Morphological characteristics of mucinous cancer of the breast containing endocrine cells].
It was established that mucus-forming mammary gland carcinoma containing endocrine cells may have a structure of an ordinary colloid mammary gland carcinoma or carcinoid carcinoma with mucus formation. The presence of amyloid in the stroma of colloid carcinoma containing endocrine cells may serve as an additional sign of the endocrine cell differentiation. Simultaneous observation in the tumour cells of both mucous inclusions and endocrine granules may be regarded as a proof of an origin of epithelial and endocrine cells of the mammary gland from a pluripotent stem cell.
APUD Cells↗
[Histotopography of colon endocrine cells in the mucosal epithelium of some mammals and in man].
Histotopography of colon endocrine cells in the mucosal epithelium of adult rabbits, white rats and man was studied by light microscopy. The number of endocrinocytes in rabbit and human colon was seen to increase towards the rectum, which reflects a general tendency in mammals. In the appendices of the investigated subjects, essential distinctions in endocrine cell contents were revealed. So, in rabbits, the maximum quantity of endocrine cells (135 +/- 15 cell/mm2) was observed in the appendix if compared to other parts of the colon (except rectum), whereas in the human appendix, the number of endocrine cells is minimal (13 +/- 3 cell/mm2). In all parts of rabbit and rat caeca endocrine cell contents are similar to those in the nearby part of the colon, which suggested that according to the given parameter the caecum shows no specifity.
Adult↗
An immunohistochemical study of endocrine cells in the pancreas of the Red-bellied frog (Bombina orientalis).
The regional distribution and frequency of pancreatic endocrine cells in the red-bellied frog, Bombina orientalis, were studied by the immunohistochemical peroxidase anti-peroxidase (PAP) method using five types of specific mammalian antisera to insulin, glucagon, somatostatin, bovine pancreatic polypeptide (PP) and secretin. The frequency was calculated as the mean number of each endocrine cell type/1,000 total cells (including exocrine and endocrine cells) using an automated image analysis process. The percentage of each immunoreactive (IR) cell species to the total IR cell population was also calculated. In the pancreas of the red-bellied frog, all five endocrine cell types were demonstrated. Insulin IR cells were located in the pancreas as single cells or islet-like clusters. The latter were localized in central regions. The insulin-IR cells showed a frequency of 65.40 plus/minus 14.56/1,000 cells. Glucagon IR cells were also detected as single cells or as clusters but in the case of clusters, two distributional patterns were detected - a central core type and a marginally distributed type. They showed an abundance of 32.70 plus/minus 7.32/1,000 cells. Somatostatin-IR cells were dispersed throughout the pancreatic parenchyma as single cells, three to four cells, or clusters. The clusters were located in the marginal regions. The somatostatin-IR cell frequency was 19.40 plus/minus 6.52/1000 cells. PP-IR cells were randomly distributed throughout the pancreatic parenchyma as single cells with a frequency of 14.70 plus/minus 4.92/1,000 cells. Secretin-IR cells were demonstrated as clusters or as single cells, and as clusters they occupied the central regions. They showed a frequency of 39.60 plus/minus 10.36/1,000 cells. This is the first report of the presence of secretin-IR cells in amphibian pancreatic endocrine cells. Overall, there were 37.20 plus/minus 6.84% insulin-, 21.90 plus/minus 5.55% glucagon-, 11.60 plus/minus 4.33% somatostatin-, 8.60 plus/minus 2.72% PP- and 23.40 plus/minus 4.45% secretin-IR cells.
Animals↗
Patterns of Pan expression and role of Pan proteins in endocrine cell type-specific complex formation.
The Pan gene encodes at least two distinct transcripts, Pan-1 and Pan-2 (also known as E47 and E12, respectively), by the mechanism of alternative RNA splicing. Northern blot analyses performed on rat and mouse tissues have detected ubiquitously expressed Pan transcripts, but the abundance, distribution, and form of Pan proteins have not been clearly defined. Studies of cell lines representing endocrine, fibroblast, and lymphoid lineages using polyclonal antisera to detect E2A proteins have suggested that significant E2A protein expression is restricted to B-lymphocytes. We have developed a monoclonal antibody, Yae, which is specific for Pan/E2A proteins, and have used the Yae antibody to examine a variety of endocrine and nonendocrine cell lineages for differences in Pan/E2A protein expression, subcellular localization, and heteromeric complex formation. In contrast to previous results obtained using polyclonal antiseras to detect Pan/E2A proteins, we report comparable levels of Pan proteins in GH/PRL- and insulin-producing, B- and T-lymphocyte cells. IEF-1, a pancreatic beta-cell type-specific complex believed to regulate insulin expression, is demonstrated to consist of at least two distinct species, one of which does not contain Pan molecules. Although it has been postulated that pituitary endocrine cells and pancreatic endocrine beta-cells share identical Pan/E2A complexes, native-Western analyses of pituitary and endocrine beta-cells detect Pan proteins in distinct cell type-specific complexes.
Animals↗