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PubMed1992

Regeneration of pancreatic endocrine cells in interferon-gamma transgenic mice.

We have shown that the pancreatic duct cells of IFN-gamma mouse are actively multiplying and that many duct cells differentiate to become endocrine cells. This islet regenerating process closely parallels the islet development during normal organogenesis in the fetus and offers a model for studying the cell lineage relationships of islet cells. The subject has received wide interest and intensive research in recent years. One of the noteworthy results of this study is the finding that duct cells retain the ability to proliferate and to differentiate into islet cells. Under normal conditions, duct cells do not continue to multiply or to differentiate. The results suggest that in the transgenic mice, the progenitor cells of embryonic multipotential duct cells transform into adult cells, but in the presence of appropriate signals or stimuli can resume their multipotential property. The appearance of hepatocytes indicates that while the cell proliferation observed largely results in endocrine cells, other differentiation pathways are occasionally possible. We also detect a few large cells containing albumin and alpha-fetoprotein in the periductal area. Pancreatic hepatocytes have also been observed in the rat after recovery from copper deficiency diet. Thus, the regeneration of islet cells in transgenic mice provides a model system for the study of factors modulating the growth pattern as well as the differentiation pathway.

Animals↗
PubMed2000

Laryngeal endocrine cells: topographic distribution and adaptation to chronic hypercapnic hypoxia.

The morphology, topographic distribution, effects of denervation, and exposure to hypercapnic hypoxia of endocrine cells were examined in rat larynx. The endocrine cells, which were immunoreactive for protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP), were observed within the epithelial layer of the laryngeal cavity and in the laryngeal gland, while solitary endocrine cells with apical and/or basal cytoplasmic processes appeared near the glottis. After denervation of the left cervical vagosympathetic trunk and the superior laryngeal nerve, the number of mucosal endocrine cells in the denervated side was not significantly different from that in the intact side. After exposure to hypercapnic hypoxia for 3 months, the number of endocrine cells with PGP 9.5 and CGRP was markedly increased. In conclusion, the secretion of laryngeal endocrine cells may be stimulated by CO2 rather than O2. Furthermore, the endocrine cells and the sensory and autonomic nervous system may regulate each other by an axon reflex mechanism. Endocrine cells appear to play a very important role in the local regulation of the laryngeal mucosa.

Animals↗
PubMed2001

An immunohistochemical study of metaplastic endocrine cells in human gallbladder cancer.

BACKGROUND/PURPOSE: In order to better understand the genesis of gallbladder cancer, we investigated the metaplastic changes and the presence of endocrine cells in mucosal tissue in the tissues of 100 patients with cholecystitis and 50 patients with gallbladder cancer. METHODS: All the tissue samples were submitted to Hematoxylin-eosin and Alcian blue-periodic acid-Schiff stain. To identify endocrine cells, we utilized Grimelius or Fontana-Masson stain. To detect intestinal hormones, we used streptavidin-biotin staining. If a given tissue sample presented with goblet cells or pseudopyloric cells, we determined that it was undergoing metaplasia. To locate a focus of endocrine cells, we used the presence of argyrophil cells and argentaffin cells. RESULTS: Metaplastic changes and endocrine cells were observed in 50% or more of the studied tissues that had been sampled from the lesions of chronic cholecystitis, and from the tumor and nontumor sites of gallbladder cancer. The tissues sampled from chronic cholecystitis patients showed endocrine cells releasing gut hormones, and the incidence of tissue presenting with such hormone-secreting cells tended to increase with the degree of metaplasia. The tissues sampled from the gallbladder cancer patients also showed endocrine cells, but the incidence in these tissues was not significantly correlated with the degree of metaplasia. In the tissue sampled from gallbladder cancer patients, the degree of metaplasia and the incidence of the tissues presenting with endocrine cells was not significantly different from the corresponding results obtained from chronic cholecystitis tissues. However, tissues presenting with endocrine cells occurred more frequently in samples from nontumor sites than in samples from chronic cholecystitis sites. The incidence of metaplastic cells and of endocrine cells correlated closely with the genesis of highly differentiated cancers. Lysozyme, a nonspecific defensive factor against infections, was frequently observed in the tissues sampled from patients with chronic cholecystitis as well as those with gallbladder cancer. CONCLUSIONS: Although metaplastic changes and endocrine cells were observed in the tissues of chronic cholecystitis as well as gallbladder cancer, these markers were most frequently observed in nontumor sites close to the tumors themselves, suggesting that these markers are closely involved in the genesis of gallbladder cancer.

Adult↗
PubMed2003

Influence of enteric helminths on the distribution of intestinal endocrine cells belonging to the diffuse endocrine system in brown trout, Salmo trutta L.

The presence of intestinal helminths in the alimentary canal of brown trout, Salmo trutta L., can alter the number of cells that synthesize modulatory peptides. A total of 167 brown trout were collected from tributaries of the River Brenta (northern Italy), of which 119 (71.3%) specimens were infected with enteric helminths, 28 with the acanthocephalan Pomphorhynchus laevis Müller, 1776 with intensity of infection ranging from 1 to 162 (18.57 +/- 30.79) worms per host and 67 fish with the cestode Cyathocephalus truncatus Pallas, 1781. Intensity of infection with C. truncatus ranged from 1 to 85 (6.87 +/- 12.59) per fish. In 24 fish there were concurrent infections of both species of helminths. The caecal and middle regions of the intestine were the most heavily parasitized. Immunohistochemical tests showed a decrease in endocrine cells (ECs) of the diffuse endocrine system (DES) positive to gastrin, cholecystokinin-8, bombesin and secretin antisera in the intestine of the infected trout. The number of ECs immunoreactive to anti-glucagon serum did not show differences in the digestive tract of uninfected brown trout and in conspecifics parasitized with P. laevis. The density of cells containing glucagon-like material was low in the fish parasitized with C. truncatus. The results suggest that endoparasitic helminths induce alterations in the DES of infected S. trutta.

Animals↗
PubMed1986

Gut endocrine cell population in coeliac disease estimated by immunocytochemistry using a monoclonal antibody to chromogranin.

Abnormalities of gut endocrine responses, as well as changes in the number of different endocrine cell types, have been reported convincingly in coeliac patients. Nevertheless, no estimation of total numbers of gut endocrine cells has yet been made in well defined groups of coeliacs. In this study, we have visualised all endocrine cell types in jejunal biopsies from coeliac patients with active and quiescent disease as well as in controls, using a monoclonal antibody to chromogranin. This protein was purified originally from bovine adrenal medulla and is known to be a reliable marker for all endocrine cells of the gut. The following groups were considered: (a) nine coeliacs with active illness, (b) 10 coeliacs under gluten-free diet, (c) eight coeliacs receiving gluten challenge, (d) five non-coeliacs (controls). Histological (haematoxylin and eosin) and immunocytochemical (peroxidase anti-peroxidase) stains were applied to 3 micron paraffin sections. Quantitative estimation of endocrine cell density was made using four different methods in order to evaluate the results fully (number of cells/mm2, number of cells/visual field, number of cells/8 crypts-villi, number of cells/unit of length of muscularis mucosae). In patient groups (a) and (c), coeliacs with active disease and coeliacs on gluten challenge diet respectively, a significantly higher number of endocrine cells was observed in comparison with normal controls (group d). In group (b) patients, coeliacs on gluten-free diet, no significant changes in the number of endocrine cells were observed in comparison with controls. Our results show that a significant increase in endocrine cell density exists in coeliacs with active illness (groups a and c), in comparison with controls. This condition is resolved in coeliacs receiving a gluten-free diet (group b).

Antibodies, Monoclonal↗
PubMed2002

Amphibian melanotrophs as a model to analyze the secretory plasticity of endocrine cells.

Precise regulation of hormone secretion from endocrine cells is of critical importance for the maintenance of animal homeostasis. This is partly enabled through the ability of endocrine cells to adapt dynamically their secretory activity to the physiological demands through complex functional changes. Such a secretory plasticity results from coordinated adaptive changes at several levels of cell function, including hormonal gene expression and biosynthesis, hormone processing, trafficking, storage and release, expression of membrane receptors, activation of signaling pathways, etc. Integration of all these processes at the single cell level defines the secretory status of each of the individual cells producing a given hormone, whose coordinated activity ultimately determines the response of the whole endocrine gland. This short review summarizes our most recent findings on the cellular and molecular elements and mechanisms underlying the secretory plasticity of endocrine cells, obtained from the analysis of distinct aspects of melanotroph cell function.

Animals↗
PubMed2004

Quantitative study of pulmonary endocrine cells in fetal, postnatal and adult sheep.

Using light microscopic immunohistochemistry, neuron-specific enolase (NSE)-positive endocrine cells were quantitatively analyzed in the sheep lung during different stages of development from the canalicular stages to adulthood. In all stages, NSE-positive endocrine cells were usually located in the bronchi and bronchioles as solitary cells, although a few NSE-positive cell clusters, the so-called neuroepithelial bodies, were found in some places. The number of NSE-positive endocrine cells decreased with advanced stages of gestation. In the late alveolar stage, the number of NSE-positive endocrine cells reached its bottom during the fetal period. There was a gradual upturn after birth. The overall pattern of growth and differentiation of the endocrine cells is most likely species-related and depends on the state of airway development; the number of the endocrine cells of almost all animals, excluding the sheep, in relation to the size of the lung reaches a peak in the late fetal and early neonatal periods and decreases shortly thereafter. NSE-positive endocrine cells were also predominantly located in the large airways during the early stage of development (canalicular stage), and were found more frequently in the small peripheral airways towards the term. These results show the number of NSE-positive endocrine cells in the sheep to be different from that seen in other species.

Age Factors↗
PubMed1998

Effect of ageing on colonic endocrine cell population in mouse.

BACKGROUND: Dysmotility in the gastrointestinal tract increases with age. Colonic endocrine cells play an important role in regulating intestinal secretion and motility. The objective was to study possible age-related changes in the colonic endocrine cells of an animal model. METHODS: The colonic endocrine cells in four different age groups of mice were investigated by immunocytochemistry and quantified by computerized image analysis. The ages of these groups were 1, 3, 12 and 24 months old. RESULTS: The numbers of peptide YY (PYY), enteroglucagon and serotonin immunoreactive (IR) cells in 1-month-old mice were significantly increased compared with those of 3-month-old mice. Similarly, the numbers of these cells were significantly greater in 12- and 24-month-old mice than in 3-month-old mice. The cell secretory index (CSI) of enteroglucagon and serotonin IR cells was higher in 1-, 12- and 24-month-old mice than in 3-month-old mice. There was no significant difference between the different age groups regarding the CSI of PYY IR cells, nor was there any statistical difference between females and males in all endocrine cell types regarding numbers and CSI. CONCLUSION: It is suggested that the increase in colonic endocrine cells prior to puberty might reflect the role of gut hormones in the development of the gastrointestinal tract. It is speculated further that the increase in colonic endocrine cells with ageing may compensate for increased receptor resistance and/or weakened response of effector organs. It is suggested that the increase in numbers and unchanged CSI of PYY cells with advancing age may be responsible for the slow colonic transit and constipation, both of which increase with age.

Aging↗
PubMed1990

Endocrine cells and brush cells at the bronchiolo-alveolar junctions of neonatal Syrian hamster lungs.

Endocrine cells and brush cells at the bronchiolo-alveolar junctions of the lung of neonatal hamsters were studied by transmission electron microscopy. On both sides of the junctions (bronchiolar and alveolar), clusters of endocrine cells occur as neuroepithelial bodies (NEB). A few solitary endocrine cells are also present at the alveolar sides of the junctions. Some endocrine cells reach from the basement membrane to the air space but the area of apical cell membrane exposed to the airway is small as the cells are largely covered by Clara cells in the bronchioles and by thin attenuations of alveolar type 1 cells in the alveoli. Some Clara cells around NEB contain cytoplasmic lamellar bodies, similar to those characteristically associated with alveolar type 2 cells. A few brush cells are also seen at both sides of the junctions. Long wide microvilli with filamentous cores extend from the apices of the brush cells. Endoplasmic reticulum and Golgi apparatus are moderately developed. Well-developed bundles of intermediate filaments course throughout the cytoplasm of some of the brush cells. The functions of endocrine cells and brush cells are unknown. However, the presence of these cells at the bronchiolo-alveolar junctions of neonatal hamster lungs suggests a role in regulation of respiratory function.

Animals↗
PubMed1983

Endocrine cells in the prostate gland, urothelium and Brenner tumors. Immunohistological and ultrastructural studies.

Endocrine cells are a normal constituent of the prostate gland, prostatic urethra and urinary bladder mucosa. Positive results using immunohistochemical technics were obtained only with antiserotonin antibodies. In normal tissues, there was a close similarity between the distribution of argyrophilic cells (Grimelius) and serotonin-storing cells. Some striking features were the patchy distribution of endocrine cells, the presence of slender cytoplasmic processes occasionally reaching the luminal surface and the paucity of specialized cells in bladder mucosa. It is unlikely that endocrine cells participate in conventional neoplasms of prostate and bladder. Exceptions are lobular hyperplasia, certain adeno-carcinomas of prostate and inverted papilloma of bladder. An ultrastructural study permitted the distinction of two types of endocrine cells characterized by a different morphology of their granules. Another relevant finding was the presence of serotonin-storing cells in Brenner tumors. The latter observation emphasizes the close similarity between this neoplastic epithelium and urothelium. This implies that endocrine cells may be of mesodermal derivation.

Brenner Tumor↗
PubMed2003

[Endocrine cell of the cow colonic mucosa].

The epithelium of colon mucosa of the adult cow was studied using the methods of light and electron microscopy to demonstrate the endocrine cells. Individual fluctuations of the endocrine cell content was noted as well as an increase in the total number of endocrine cells in the rectal epithelium, that was more pronounced tan in other vertebrates. Four types of endocrine cells were demonstrated: EC, L, D, D1. The variability of dimensions and shape of granules in EC-cells was found to be less tan in other vertebrate species. In some D1-cells the mucous granules were observed along with endocrine ones, thus indicating the presence of "mixed" exo-endocrine cells. Undifferentiated endocrine cells were also detected that were found at the bottom of the crypts. The features indicated above are the specific peculiarities of endocrine apparatus of the mucosal epithelium of cow colon.

Animals↗
PubMed1978

[Endocrine cells in cancer of the ampulla of Vater].

Histochemical examinations of 28 cancers of Vater's papilla detected argirophilic cells in 7 (25%) and argentaffinic cells in 3 (10.8%) tumors. Neoplastic endocrine cells occurred most frequently in structures of the highly differentiated papillary and tubular adenocarcinoma. The analysis of the qualitative composition of mucus produced by these tumors showed the likelihood of detection of endocrine cells in cancer of Vater's papilla to increase with higher secretion of acid mucopolysaccharides and to decrease with a higher portion of sulphomucines in them. The occurrence of impregnated endocrine cells and non-sulphated acid mucopolysaccharides in cancers of Vater's papilla appears to indicate the differentiation of the tumor tissue in the direction of the intestinal epithelium. The regular participation of argentaffinic and argirophilic cells in the development of intestinal tumors, in particular, cancer of Vater's papilla is in favour of the entodermal origin of endocrine cells of the gastrointestinal tract.

Adenocarcinoma↗
PubMed1975

Electron microscope study on endocrine cells and tumor cells in the glandular stomach of Praomys (mastomys) natalensis.

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.

Animals↗
PubMed1975

Ultrastructure of endocrine cells in metaplastic epithelium of human gall bladder.

Two endocrine cell types were found in the metaplastic epithelium of gall bladders removed for gall stones. The endocrine cell type I resembled the EC (enterochromaffin) cell of the normal stomach mucosa. The homogeneous and electron-dense secretory granules were variable in size and shape and mainly located in the sub-nuclear cytoplasm. The endocrine cell type II was similar to the ECL (enterochromaffin-like) cell of the human stomach. The secretory granules were almost exclusively present in a subnuclear location, and were round and homogeneous in size. The secretory material was slightly granular and often there was a clear zone (halo) between the granule core and the limiting membrane. A rich network of microfilaments in the cytoplasm, especially around the nucleus, was typical of the type II endocrine cell. Both cell types were closely related to the basement membrane and the capillaries underneath.

Cholelithiasis↗
PubMed1990

Gastric endocrine cells share a clonal origin with other gut cell lineages.

There has been considerable debate about the ontological origin of gut endocrine cells as being either from the neural crest (or primitive epiblast) or from the endodermal stem cell. We have attempted to define the ontological origin of endocrine cells by applying an experimental system that uses a marker to identify one of the two phenotypes present in chimaeric mice as suggested by Ponder et al. (1985). This study involved two separate experiments. The first made use of the unique staining properties of Dolichos biflorus agglutinin (DBA), a lectin that binds to the N-acetyl galactosamine sugar residues present on the surface of C57Bl mouse gut, but absent from RoRIII mouse gut, in C57Bl----RoIII mouse chimaeras at the ultrastructural level. A four-stage procedure for staining at the EM level was developed. Although mature villous endocrine cells stained for DBA, immature endocrine cells did not, either in the positive crypts of chimaeric mouse gut or in gut from C57Bl positive controls. Thus a second marker was chosen. This experiment combined immunocytochemistry (to identify gastric antral gastrin cells chosen as a representative neuroendocrine cell) with in situ DNA hybridization for the mouse male chromosome repeat sequence PY 353 (to identify XY cells) in XX----XY chimaeric mice. This study showed that the sex chromosomal pattern in the gastrin cells parallels that of other cells in the same gastric gland and therefore are clonal with them. This suggests that gut endocrine cells share a common stem cell with other epithelial cell lineages in the antrum and are endodermally derived.

Animals↗
PubMed1977

The ultrastructure of endocrine cells in the corpus of the stomach of human fetuses.

The ultrastructural development of endocrine cells from the corpus of fetal human stomachs is described. Samples were taken from fetuses ranging in fertilization age from 6-8 to 22 weeks. The identifying features used for the classification of the various types of endocrine cells were their basal locations in the epithelium, the presence and morphology of their characteristic granules and the sizes of the mitochondria. Five types of endocrine cells with specific granules were found:D, EC, ECL, AL and D1. The type and number of endocrine cells increased as development proceeded. The endocrine cells were confined to the epithelium, they did not reach the lumen and they appeared to develop in situ. The D, EC and ECL cells were the most numerous. The fetal endocrine cells resembled morphologically those found in the stomachs of various adult animals. The EC, ECL and D1 cells contained small slender mitochondria with few cristae. Intramitochondrial granules were absent in all the cell types. Agranular electron-lucent cells with small mitochondria were considered to be immature endocine cells. The advanced stage of differentiation observed in these cells suggest that they may be capable of producing and storing biogenic amines and polypeptide hormones. Their possible involvement in the synthesis of serotonin, enteroglucagon and intrinsic factor is discussed.

Endocrine Glands↗
PubMed1997

Colonic endocrine cells in inflammatory bowel disease.

OBJECTIVES: To study colonic endocrine cell types in patients with ulcerative colitis (UC) and Crohn's disease (CD). SETTING: Departments of Medicine and Pathology, University Hospitals, Umeå and Uppsala, Sweden. SUBJECTS: Seventeen patients with UC (seven females and 10 males) and 11 patients with CD (five females and six males). Twenty-two patients (eight females and 14 males) operated on for colon carcinoma and without signs of inflammatory bowel disease were used as controls. MEASUREMENTS: The colonic endocrine cell types were identified by immunohistochemical methods and quantified by computed image analysis. RESULTS: The areas of the argyrophil cells as well as those immunoreactive to chromogranin A and serotonin were significantly increased in patients with both UC and CD, compared with those in the controls. In patients with CD, the areas of polypeptide YY(PYY)- and pancreatic polypeptide (PP)-immunoreactive cells were significantly reduced, whilst the area of enteroglucagon-immunoreactive cells was increased. There was no statistical difference in endocrine cell area between specimens with slight versus severe inflammation, except for PYY and enteroglucagon cell areas in patients with CD. Whilst the former cell area decreased, the latter increased in specimens with severe inflammation. The mean cellular area for each endocrine cell type did not differ between the controls and patients with UC or CD. CONCLUSIONS: The increase in the serotonin-immunoreactive cell area in patients with both UC and CD might be one of the factors causing reduced colonic contraction and increased intraluminal pressure observed in patients with inflammatory bowel disease. Furthermore, in patients with CD, the decreased PYY-immunoreactive cell area may explain the decreased absorption and increased secretion found in these patients.

Adolescent↗
PubMed1999

Differential distribution of isoforms of Leucophaea tachykinin-related peptides (LemTRPs) in endocrine cells and neuronal processes of the cockroach midgut.

Five isoforms of tachykinin-related peptides (TRPs), designated LemTRP-1-5, have been identified in the midgut of the cockroach Leucophaea maderae. These peptides have a conserved C-terminus hexapeptide (GFX1GX2Ramide; X1 and X2 are variable residues) and variable N-termini. Here, we address the question of whether these five isoforms are all colocalized in the two types of cells in the cockroach midgut, the endocrine cells and the neuronal processes. We also investigate whether the N-terminally extended isoforms LemTRP-2 and -3, which contain putative endoproteolytic cleavage sites, are expressed in intact form or are cleaved in the midgut cells. To this end, we used two approaches. (1) Extracts from portions of the midgut containing each of the cell types were subjected to reverse-phase high performance liquid chromatography (HPLC) and the fractions monitored in a radioimmunoassay (RIA) with an antiserum to the conserved C-terminus of insect TRPs. (2) Antisera were raised to the variable N-termini of the extended LemTRP-2 and -3 and used for immunocytochemistry. The HPLC-RIA and immunocytochemical findings indicate that LemTRP-1 and 4-5 are present in the neuronal processes and in endocrine cells of the midgut proper and of the gastric cecae. The two extended forms LemTRP-2 and -3 display a differential distribution: LemTRP-2 was found in endocrine cells of midgut and gastric cecae, but not in neuronal processes, whereas LemTRP-3 was seen in neuronal processes and endocrine cells of the midgut proper, but not in the gastric cecae. LemTRP-3 and -4 have not been identified in the brain, suggesting further cell- and tissue-specific expression of LemTRPs. The mechanisms behind the cell-specific expression of the LemTRPs are not yet understood, but the demonstration of differential distribution of the peptide isoforms provide a first indication that the isoforms may have different actions.

Animals↗