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[Quantitative characteristics of the endocrine cells of the duodenal glands of Carnivora].

In the duodenal glands of the Carnivora investigated endocrine elements have been revealed, a part of them is presented as serotonin-producing EC-cells. Endocrine cells are situated in terminal parts and in glandular ducts, among them elements of open and close types are distinguished. Distribution of these cells in the glandular lobules is subjected to the distal gradient regularity, specific for the gastrointestinal tract mucosal membrane. Amount of endocrinocytes in the glands is much less than in the gut crypts. There is no correlation between distribution of the endocrine cells in the glands and in the crypts. The results of unifactor analysis of variance demonstrate a slight effect of the taxonomic position of the species on the number of endocrine cells in the duodenal glands. The proper endocrine apparatus of the duodenal glands is supposed to produce a local regulatory influence on the secretory activity of exogenic glandulocytes, as well as ensure humoral connections of the duodenal glands with other parts of the gastrointestinal tract.

Animals↗

Phagocytotic removal of apoptotic endocrine cells by folliculostellate cells and its functional implications in clusterin accumulation in pituitary colloids in helmeted guinea fowl (Numida meleagris).

The different cell types in the anterior pituitary behave as dynamic populations. The gland maintains a continuous renewal of cells to ensure a dynamic balance between cell division, differentiation, growth arrest and apoptosis. Apoptosis is a frequent event in the anterior pituitary in which unwanted cells are eliminated without affecting neighboring cells. We examined the link between apoptosis and the occurrence of colloids in the guinea fowl (Numida meleagris) pituitary gland and the relationship of clusterin accumulation in the colloids. S-100 positive folliculostellate (FS) cells were found surrounding colloids. Apoptotic cells detected by single stranded DNA (ssDNA) immunohistochemistry were observed in the whole anterior pituitary and preferentially near colloid masses. Clusterin protein was detected in endocrine cells, FS cells and in the colloids. In situ hybridization showed clusterin mRNA in endocrine cells and FS cells. Simultaneous localization was performed to determine whether clusterin mRNA and ssDNA within anterior pituitary was present within the same cell. Clusterin mRNA was not detected in apoptotic cells but was present in neighboring surviving cells. At the ultrastructural level, numerous endocrine cells at different stages of apoptosis were found phagocytosed by FS cells. Our results suggest that clusterin is produced by endocrine cells for cytoprotection before death. Apoptotic endocrine cells are phagocytosed by FS cells and digested by their lysosomal enzymes. In FS cells, clusterin interacts and aggregates with by-products of digestion that subsequently become stored in colloid as a residual body.

Animals↗

Gastric PDX-1 expression in pancreatic metaplasia and endocrine cell hyperplasia in atrophic corpus gastritis.

The homeodomain transcription factor PDX-1 plays a key role in endocrine and exocrine differentiation processes of the pancreas. PDX-1 is also essential for differentiation of endocrine cells in the gastric antrum. The role of PDX-1 in the pathogenesis of endocrine cell hyperplasia and pancreatic metaplasia in corpus and fundus gastritis has not been evaluated. By immunohistochemistry and double-immunofluorescence, we investigated the expression of PDX-1 in 10 tissue specimens with normal human gastric mucosa, nonatrophic and atrophic gastritis and in pancreatic metaplasia, respectively. In normal corpus mucosa and in nonatrophic corpus gastritis, PDX-1 was mainly absent. In pancreatic metaplasia, PDX-1 was found in metaplastic cells and in adjacent gastric glands. In contrast to normal gastric corpus mucosa, PDX-1 could be strongly detected in the cytoplasm of the parietal cells surrounding metaplastic areas. Furthermore, PDX-1 expression was found in hyperplastic endocrine cells and in the surrounding gastric glands in chronic atrophic gastritis. Hyperplastic endocrine cells coexpressed the beta-subunit of the gastric H,K-ATPase. We conclude that PDX-1 represents a candidate switch factor for glandular exocrine and endocrine transdifferentiation in chronic gastritis and that an impaired parietal cell differentiation might play a key role in disturbed gastric morphogenic processes.

Adult↗

A tissue-specific enhancer in the rat-calcitonin/CGRP gene is active in both neural and endocrine cell types.

The calcitonin gene related peptide (CGRP) gene is a complex transcription unit that is expressed in a highly restricted pattern in both the nervous system, particularly in sensory ganglia and brainstem, and in the thyroid C cells of the endocrine system, with tissue-specific alternative RNA processing events generating transcripts encoding either the hormone, calcitonin, or the neuropeptide, CGRP. This pattern of expression in neural and endocrine tissues raises the question whether similar or distinct genomic elements are responsible for activation in both neural and endocrine cell types. We have identified a complex enhancer element, located more than 1 kilobase 5' of the transcription initiation site of the calcitonin/CGRP gene that functions in cells of neuronal or C cell origin, but not in any other cell type tested. At least two complementary regulatory sequences are required for the function of the cell-specific enhancer.

Animals↗

[Unique papillary cystadenocarcinoma of the prostate with endocrine cells].

Histological examination of prostatic tumour of a man who died at the age of 71, revealed dark-cell small-acinar carcinoma with scattered papillary cystadenocarcinomatous structures. The latter, apart from two types of epithelial cells (dark granular and clear cells) contained argyrophilic endocrine cells detected by Grimelius' staining. These cells were absent in the dark-cell small-acinar areas. It is suggested that acinar and cystadenopapillary structures differ in their histogenesis.

APUD Cells↗

The endocrine cells of the proper gastric glands of adult ox.

Unlike histochemical analysis, which permits only the certain identification of "EC" cells, an ultrastructural study on the bovine proper gastric glands shows the presence of "EC" cells of the gastric type, "ECL" and "D1" cells with the usual characteristics of their respective secretory granules. There are besides other cells whose granules show morphological and cytochemical characters resembling those of the "X" cells. All these endocrine cells are lacking in luminal connection and appear to be sorrounded by a folding of the cytoplasm of one or two exocrine cells, the most commonly being the parietal cells. We cannot identify the "A" cells: their absence may be a morphological confirmation of the lack of extractable glucagon in bovine abomasum. The ultrastructural analysis, therefore, enables us to emphasize in this species a correspondence with the proper gastric glands of the monogastrics.

Abomasum↗

Histamine containing endocrine cells in the human stomach.

Histamine and chromogranin A-immunoreactive cells were studied in the mucosa of the human stomach. Cells reacting to both histamine and chromogranin A-antibodies (histamine containing endocrine cells), were demonstrated by double immunostaining and found to be restricted to the oxyntic mucosa. Histamine containing cells that did not stain with chromogranin A-antibodies were numerous throughout the stomach. Of the histamine immunoreactive cells in the oxyntic gland area 22% reacted with antibodies against chromogranin A. Histamine containing endocrine cells constituted 44% of the total number of endocrine cells in the oxyntic mucosa. These findings suggest that the histamine containing endocrine cells in the human stomach are identical with the so called enterochromaffin like cells.

Adult↗

[Endocrine cells in Walthard's cell rests].

Walthard cell nests have been systematically examined for the presence of some endocrine cell types using histochemical and immunohistochemical techniques. Serotonin immunoreactive cells were the only endocrine cells demonstrated in this site. These cells were immunocharacterized using a peroxidase-antiperoxidase technique. This finding reinforces the homology with transitional epithelium (urothelium) of urinary tract and Brenner tumors. In all these structures, the abundance of endocrine cells seems to be related to the intensity of the proliferative process affecting the transitional epithelium.

Endocrine Glands↗

Hamster pulmonary endocrine cells with positive immunostaining for calbindin-D28K.

We have examined the distribution of calcium-binding proteins (CaBPs) in adult and fetal lungs of Syrian golden hamsters (Mesocricetus auratus) using immunostaining with confocal laser microscopy and electron microscopy. Single and grouped (neuroepithelial body; NEB) endocrine cells were distributed from bronchi to alveolar ducts in the adult lung. Serial frozen sections immunostained for CaBPs in combination with immunostaining for endocrine markers such as calcitonin gene-related peptide, serotonin, PGP9.5, and synaptophysin revealed that positive immunostaining for calbindin-D28K (CB-D28K) was seen in single endocrine cells and NEBs. However, other so-called EF-hand family CaBPs, parvalbumin and calretinin, were not detected. Electron microscopically, positive immunoreaction for CB-D28K was mainly in the organelle-free cytoplasmic matrix of endocrine cells, and partly in nuclei and associated with secretory granules and endoplasmic reticulum. In fetal developing lungs, endocrine cells appeared first on gestational day 13, and they were positive for all the endocrine markers used. However, pulmonary endocrine cells were positively immunostained for CB-D28K from gestational days 15 and 16 onward. In summary, our observations suggest that CB-D28K is a useful marker for endocrine cells of the lung, and CB-D28K could function as a mediator of endocrine stimulation or calcium homeostasis in pulmonary endocrine cells.

Animals↗

[The endocrine cells of the gastrointestinal epithelium and the metabolism of biogenic amines in the gastrointestinal tract (author's transl)].

After a review on the historical development of morphological investigations of entero-endocrine cells, dating back to 1870, a detailed synoptical review of the current stage of findings in this field is given. At the present time nine different endocrine cell types can be distinguished in the epithelium of the gastrointestinal tract. Criteria for this differentiation are properties concerning specific staining methods, aldehyde-induced fluorescence, immunohistochemistry, and ultrastructure. From present results it is obvious that distinct cell types are responsible for the synthesis of defined polypeptide hormones (e.g. gastrin, secretin, enterogastrone). The metabolism of amines, in relation to the endocrine cells of the gastrointestinal tract is of particular interest here. Points investigated include the uniqueness of endocrine cells, with regard to the metabolism of biogenic amines ("APUD-cells") and the possibility of serotonin synthesis by a definite cell type, i.e. by the EC-cell ("enterochromaffin" cell). In our experimental animal, male Wistarrats, seven different entero-endocrine cell types can be discerned by ultrastructural means: EC-, ECL-, G-, AL-, EG-, D- and D1-cells. The I-cell (found in other species) can hardly be distinguished from the AL-cell by ultrastructural means and the S-cells, as found in other species, are not to be found at all. Only some of the cited cell types can be seen by fluorescence microscopy. After formaldehyde-treatment of the tissue, the "enterochromaffin" cell shows a yellow, serotonin-specific fluorescence. This cell corresponds in shape, number and distribution to the ultrastructurally defined EC-cell. EC-cells are found predominantly in the pyloric region and the duodenum and less frequently in the middle- and hindgut and the cardiac region; seldomly EC-cells are encountered in the oxyntic gland area of the stomach. In the rat gastro-intestinal tract, number and fluorescent intensity of EC-cells does not always correspond with the serotonin content of a certain region--sometimes the level of serotonin is largely determined by the mast cells, which in the rat also contain serotonin. For example, the high serotonin content of the oxyntic gland area, which contains very few EC-cells, has to be contributed nearly exclusively to mast cell serotonin. Mast cells can be domonstrated by fluorescence microscopy, due to their histamine content, after treatment of the tissue with o-phthalaldehyde (OPD). It seems likely that the histamine content, especially that of the so-called "atypical mast cells" of the mucosa, is inversely related to their respective serotonin content. --In addition to mast cells, OPD-treatment leads to a fluorescence in some of the entero-endocrine cells of the gastrointestinal epithelium. In the gastric epithelium these fluorescing cells should be regarded as histamine-containing ECL-cells and glucagon-containing AL-cells while in the colonic epithelium they are considered to be glucagon-containing AL-cells...

5-Hydroxytryptophan↗

Endocrine cells in adenocarcinomas and their prestages in the glandular stomach and duodenum of rats after MNNG administration. Histochemical, electron microscopical and radioimmunological studies.

Tumours of the glandular stomach and upper small intestine were induced in rats by oral administration of MNNG. In most cases the lesions were identified histologically as adenocarcinomas and their prestages, such as polypeous and downward growing adenomatous hyperplasias. Out of 48 adenomatous hyperplasias and adenocarcinomas of the stomach and 24 well differentiated adenocarcinomas of the small intestine, we observed argyrophilic cells in nearly the half of the cases. Endocrine cells were also identified by electron microscopy. The frequency of endocrine cells was reduced with decreasing degree of tissue differentiation. In poorly differentiated carcinomas, including signet ring cell carcinomas, no argyrophilic cells were found. Out of 10 adenomatous hyperplasias and tumours of the stomach investigated immunohistochemically, 5 cases showed gastrin producing cells. Most of these animals were radioimmunologically characterized by strongly elevated serum gastrin levels. Derivation and potential relevance of the endocrine cells in tumours are discussed.

Adenocarcinoma↗

Pathologic changes of endocrine cells in chronic atrophic gastritis. An ultrastructural study on peroral gastric biopsy specimens.

In the course of an ultrastructural study on peroral gastric biopsy specimens that were obtained from patients with chronic atrophic gastritis, peculiar pathological changes of endocrine cells were observed and correlated with functional and hormonal data on the patients. An increased number of G (gastrin) cells was found in hypergastrinemic patients. These cells could be divided into a "light" (probably hyperfunctioning) and a "dark" (probably exhausted) type. The light type of cell was prominent regardless of the concomitant gastrin blood levels. The G cells found within the fundic region were always localized within the areas of pyloric metaplasia. Focal micronodular proliferation of antral enterochromaffin cells (EC) was often seen. A proliferation of the closed type of endocrine cells of the fundic mucosa was observed only in patients with elevated gastrin concentrations. In the present study, these cells were identified as enterochromaffin-like cells (ECL). No substantial changes were found in the D and D1 cells. The endocrine cells seen in metaplastic intestinal epithelium exhibited ultrastruct characteristics of at least three different types of intestinal endocrine cells (EC, L, and S cells).

Adult↗

An electron microscopic radioautographic identification of the APUD endocrine cells in the rat gastric pyloric glands.

The rat stomach was shown some years ago to contain numerous endocrine cells with APUD ability--cells that could take up the amino acids L-5-hydroxytryptophan (5-HTP) or L-dihydroxyphenylalanine (L-DOPA) and could decarboxylate them to their respective amines, 5-hydroxytryptamine (5-HT, serotonin) and dopamine, by means of the enzyme DOPA-decarboxylase. In a recent study, most of the APUD endocrine cells in the rat oxyntic mucosa were shown by electron microscopic radioautography to be the enterochromaffinlike cells, while the A-like cells were shown to lack APUD ability. To identify the APUD cells in the pyloric mucosa, pieces of rat pylorus were incubated in organ culture with 3H-5-HTP and were processed for light microscopic and electron microscopic radioautography. Additional specimens were incubated with 3H-5-HTP and carbidopa, an inhibitor of DOPA-decarboxylase, used to block the decarboxylation of 3H-5-HTP to 3H-5-HT, or with 3H-5-HT, used to determine where exogenous 3H-5-HT localizes in the pyloric mucosa. The 3H-5-HTP labeled all three types of endocrine cells identified within the pyloric glands--the G, enterochromaffin, and D cells. As this labeling was inhibited by carbidopa, and as exogenous 3H-5-HT labeled these cells only lightly, the labeling must have resulted from the uptake and intracellular conversion of the 3H-5-HTP of 3H-5-HT. Thus despite their morphologic differences, all rat pyloric endocrine cells possess APUD ability, a property shared by many, but not all, of the peptide- and amine-producing endocrine cells located throughout the body.

5-Hydroxytryptophan↗

Endocrine cells of the human gastrointestinal tract have no proliferative capacity.

There is compelling evidence that the epithelial cell lineage of the gastrointestinal tract are derived from a common stem cell precursor, but the details of the subsequent cellular hierarchies remain uncertain. In this context, it is important to know the arrangement of cell proliferation that gives rise to the final cell populations. In rodents, a number of studies have been performed examining the possible proliferative capacity of endocrine cells, but a wide range of technical problems makes interpretation of these data difficult. Continuous labelling studies suggest there is potential for proliferation in endocrine cells but flash labelling studies have not been conclusive. In man there are no data on this issue. We have taken advantage of the ability to perform double immunostaining for operational markers of proliferation (Ki67 antigen) and endocrine cell phenotype (chromogranin expression). We demonstrate that there are no double-labelled cells in the normal stomach, small intestine or colon of fetal, neonatal or adult humans. Moreover, no double-labelled cells are found in pathological states associated with endocrine cell hyperplasia (gastritis, ulcerative colitis). These data indicate that the normal endocrine cells of the human gut have no proliferative capacity and that, in this cell lineage, population expansion precedes differentiation.

Adult↗

Endocrine cell populations in the colon and rectum of cat, dog, and monkey: fine structure, immunocytochemistry, and distribution.

Comparative and quantitative ultrastructural studies of endocrine cells from the large bowel of European cat, beagle dog, and the monkey Callitrix jacchus were performed. The cat and monkey exhibited a roughly similar distribution of colonic endocrine cells with a frequency increasing toward the distal. On the contrary, the highest endocrine cell frequency in the dog colon was in the cecum. In the dog and monkey, enterochromaffin (EC) cells were predominant in all segments. In the cat, non-EC cells were predominant in the proximal colon. For each colonic segment, relative percentages of EC and non-EC cells appeared on the whole to be roughly stable between individuals of the same species. Three subtypes of EC cells were distinguished in each species. Non-EC cells were characterized by large variation in size and electron densities of their granules: Mean granule size per cell extended from 210 to 850 nm in cat, 310 to 770 nm in dog, and 130 to 470 nm in monkey. In each species, statistical analyses indicated that the non-EC cell population was composed of two or more subpopulations. Some similarities were found between colonic endocrine cells of the monkey and man, whereas obvious differences appeared between the two carnivorous mammals. Immunocytochemical studies demonstrated the presence of cells containing enteroglucagon, somatostatin, or a pancreatic polypeptidelike substance in the colon of the monkey and the rectum of the three mammals. Correlative immunocytochemical and ultrastructural studies showed that the three kinds of immunostained endocrine non-EC cells in each species had rather round granules, with great electron densities. Some subpopulations, morphologically distinguished, did not react to any of the antisera used. This suggests either the existence of secretory cycle in some endocrine cells or, perhaps, the presence of peptides still unknown in this part of the gut.

Animals↗

Endocrine cells in human Bartholin's glands. An immunohistochemical and ultrastructural analysis.

Endocrine cells were investigated in human Bartholin's glands by use of histochemical, immunohistochemical and ultrastructural methods. Endocrine cells represent normal constituents of these glands, being mainly distributed throughout the transitional epithelium of the major excretory duct; however, single elements are dispersed among the acinar lobules. Serotonin-, calcitonin-, katacalcin-, bombesin- and alpha-hCG-immunoreactive cells were recognized, with serotonin-immunoreactive cells predominating. Co-expression of calcitonin, katacalcin or alpha-hCG with serotonin was observed in single endocrine cells. At the ultrastructural level, these cells are richly granulated and show typical neuroendocrine features. Bartholin's glands display an endocrine profile quite similar to that of other cloacal-derived tissues.

Antibodies↗

Distribution patterns of the paraneuronal endocrine cells in the skin, gills and the airways of fishes as determined by immunohistochemical and histological methods.

The neuro-endocrine cells of fish skin and respiratory surfaces, and their bioactive secretion as far as is known, are reviewed, and compared with similar elements in tetrapods, particularly amphibians. In the skin of teleost fish, immunohistochemistry has shown that Merkel cells react for serotonin, neuron-specific enolase and enkephalins. The pharmacology is not established in dipnoans or lampreys. In some teleosts, neuromasts react for substance P and leu-enkephalins; substance P is also reported from some ampullary organs (electroreceptors). Taste buds of teleosts may react for enkephalin and substance P. Basal cells of taste buds react for serotonin and neuron-specific enolase. Some unicellular skin glands of teleosts express bioactive compounds, including serotonin and some peptides; this ectopic expression is paralleled in amphibian skin glands. The dipnoan Protopterus has innervated pulmonary neuro-endocrine cells in the pneumatic duct region with dense-cored vesicles. In Polypterus and Amia the lungs have serotonin-positive neuro-endocrine cells that are apparently not innervated. In fish gills, a closed type of neuro-endocrine cell reacts for serotonin, an open type for enkephalins and some calcium-binding proteins (calbindin, calmodulin and S-100 protein). The functions of neuro-endocrine cells in fishes await investigation, but it is assumed they are regulatory.

Animals↗

Effect of alpha-fluoromethylhistidine-evoked histamine depletion on ultrastructure of endocrine cells in acid-producing mucosa of stomach in mouse, rat and hamster.

The oxyntic mucosa of the mammalian stomach is rich in endocrine cells, such as ECL cells, A-like cells, somatostatin cells, D1/P cells and, in some species, enterochromaffin cells. The various endocrine cell types can be distinguished on the basis of their characteristic cytoplasmic granules and vesicles. The ECL cells contain numerous large secretory vesicles and relatively few, small electron-dense granules and small clear microvesicles. We have suggested that in the rat the ECL cells contain most of the gastric histamine with the secretory vesicles as the major histamine storage site in these cells. alpha-Fluoromethylhistidine is an irreversible inhibitor of histidine decarboxylase, the histamine-forming enzyme. We have previously shown that this enzyme inhibitor depletes histamine from the ECL cells in the rat and reduces the number of secretory vesicles in the cytoplasm. In the present study, we have examined whether alpha-fluoromethylhistidine affects the ECL cells in other species and whether it affects other types of endocrine cells in the oxyntic mucosa of the rat. Mice, rats and hamsters were treated with the inhibitor (3 mg/kg per h) via minipumps subcutaneously for 24 h. This treatment lowered the oxyntic mucosal histamine concentration by 65-90% and the number and volume density of the secretory vesicles by 85-95% in the ECL cells of the three species examined. In contrast, the number and volume density of granules and microvesicles were not greatly affected. No evidence was found for an effect of alpha-fluoromethylhistidine on A-like cells, somatostatin cells or D1/P cells of the rat stomach, suggesting that, unlike the ECL cells, they do not contain histamine.

Acids↗