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PubMed1988

Immunocytochemical and electronmicroscopical data on the differentiation of somatostatin-containing endocrine cells in human large intestine.

The distribution and ultrastructure of the somatostatin-containing endocrine cells in the distal large intestine of fetuses, children and adults was investigated by silver impregnation, immunocytochemical and electron-microscopical techniques. Somatostatin-containing endocrine cells in 10-14-week-old fetuses were found to differentiate very intensively. In 19-25-week-old fetuses the frequency of occurrence began to decrease and this tendency was preserved during the subsequent stages of ontogenesis. Conversely, the frequency of occurrence of argyrophil endocrine cells increased. The change in the mean diameters of the secretory granules was also studied.

Adult↗

PubMed1986

Effect of short- and long-term feeding of omeprazole on rat gastric endocrine cells.

Rats were tube-fed with omeprazole (40 mumol/kg body weight twice daily) for 30 and 60 days. As a result, fasting plasma gastrin levels were significantly elevated, while plasma somatostatin levels remained normal. Gastrin concentrations in the antral mucosa were unchanged after 30 days, but significantly elevated after 60 days. The relative stomach weight and the area of the antral and oxyntic mucosa increased significantly; however, the oxyntic mucosa thickness and the volume density of the parietal cells did not increase. Highly significant changes occurred in the endocrine cells of the antrum and corpus. The volume density of the argyrophilic (Grimelius technique) cells of the oxyntic mucosa increased time-dependently, and so did the volume density of the antral G cells, while the volume density of the antral D cells decreased. This resulted in a remarkable increase in the G/D cell ratio. All functional and morphological changes are reversed 42 days after omeprazole feeding for 60 days. The findings in the endocrine cells of the antral mucosa are explained by the omeprazole-induced permanent elevation of the intragastric pH and in the endocrine cells of the oxyntic mucosa by the following hypergastrinaemia.

Administration, Oral↗

PubMed1982

Small-granule (neuro)endocrine cells in the infracardiac lobe of a hamster lung. Number, subtypes, and distribution.

Small-granule APUD (amine precursor uptake and decarboxylation) endocrine cells were surveyed in 600 3 microns glycol methacrylate-embedded, periodic acid-Schiff (PAS)-lead hematoxylin-stained serial sections comprising 95% of the infracardiac lobe of a hamster lung. Results were confirmed by less systematic study of other hamster lungs. Positions of endocrine cells were marked on cardboard profiles of bronchi and bronchioles for assembly into a 70 X enlarged three-dimensional model from which size and branching of the airway were determined. Records were made for computer analysis of the number and staining patterns of endocrine cells, the nature of contiguous epithelial cells, and the presence of underlying smooth muscle and blood and lymph vessels. APUD cells occurred in 95% of all airways, at a mean density of six solitary cells and 10 cell clusters (neuroepithelial bodies) per millimeter of airway length, measured along the bronchial-bronchiolar long axis. Nineteen percent of endocrine cell loci (29% of all cells) were found at bronchioloalveolar portals in all regions of peripheral lung. Twenty percent of loci (28% of all cells) occurred about the origins of lateral airway branches; these included 4% of loci on carinal points of bifurcation. Two groups of APUD cells had distinctive anatomic relationships: 1) 13% of loci (20% of cells) were related to pulmonary capillaries and venules, mainly at bronchioloalveolar portals; and 2) 39% of loci (53% of cells) overlaid peribronchial muscle, mainly in larger airways where changes in diameter might affect ventilation. In this lobe, APUD cells were not related to goblet or mast cells; 74% of loci abutted Clara and/or ciliated cells, 17% great alveolar cells. Few loci were associated with pulmonary arteries and veins. Five APUD cell types were identified by PAS-lead hematoxylin staining. Types I, II, and V, with granules approximately 0.2 micron in diameter, made up 38%, 45%, and 2% of cells, respectively. Types III and IV, 10% and 5% of cells, respectively, had larger granules. Types I, II, III, and V occurred as solitary cells as well as in neuroepithelial bodies. One-third of the neuroepithelial bodies contained a single cell type; the rest were mixed. Type IV cells, with coarse lead hematoxylin-positive granules, usually were found in large neuroepithelial bodies containing two to four cell types and were never seen occurring alone. We conclude that 1) hamster lungs contain different kinds of APUD cells; 2) those likely have a variety of functions; 3) distinctions merely between solitary and clustered cells may not be significant; 4) the histophysiology of many neuroepithelial bodies probably is more complex than previously suspected; and 5) PAS-lead hematoxylin is superior to argyrophilia and amine fluorescence for light microscopic counting and analysis of pulmonary APUD cells in this species.

APUD Cells↗

PubMed2000

Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.

Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by light and electron microscopic immunohistochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previously been clarified. The localization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, we determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.

Animals↗

PubMed1998

Colonic endocrine cells in patients with carcinoma of the colon.

OBJECTIVE: To investigate the colonic endocrine cells in patients with colon carcinoma in order to establish a possible abnormality. PATIENTS: Twelve patients with colon adenocarcinoma (eight women and four men; mean age 69 years; range 52-88 years) were studied. As controls, macroscopically and histologically normal tissues from the colon of 12 patients (eight women and four men; mean age 66 years; range 34-86 years) were examined. These patients suffered from polyps, prolapsus, chronic diverticulitis, volvulus or haemorrhoids. METHODS: Macroscopically and histologically normal tissues from the colon of the patients, about 10 cm from the tumour, and of the controls were examined. Endocrine cells were immunostained with the avidin-biotin-complex method, and were quantified by computer image analysis using an automatic standard sequence analysis operation. Three parameters were used: (1) the number of endocrine cells per mm3 of epithelial cells; (2) the cell secretory index (CSI); and (3) the nuclear volume. RESULTS: The numbers of somatostatin- and serotonin-immunoreactive cells were significantly reduced in patients with colon carcinoma (P = 0.03 and 0.009, respectively). There was no difference between patients and controls regarding the numbers of PYY-, PP-, and enteroglucagon-immunoreactive cells. The CSI of somatostatin- and serotonin-immunoreactive cells were significantly decreased. There was no difference in the CSI between the patients and controls regarding PYY-, PP- or enteroglucagon-immunoreactive cells. The nuclear volumes of PYY- and enteroglucagon-immunoreactive cells increased significantly in the patients. The nuclear volume of PP-, somatostatin- and serotonin cells did not differ from those of the controls. CONCLUSION: The present results support the assumption that a disturbance in the colonic neuroendocrine system occurs in patients with colon carcinoma, which might affect the development of the tumour. The decrease in the number and CSI of somatostatin cells may account for the decrease of the colonic content of this peptide observed previously in these patients. The decrease in the number and CSI of serotonin-immunoreactive cells in patients with colon adenocarcinoma might be a method by which the body defends itself against this mitogenic substance.

Adenocarcinoma↗

PubMed1998

Altered processing of procholecystokinin in carboxypeptidase E-deficient fat mice: differential synthesis in neurons and endocrine cells.

The fat mouse strain exhibits a late-onset obesity syndrome associated with a mutation in the gene encoding carboxypeptidase E (CPE). CPE plays a central role in the biosynthesis of many regulatory peptides. Therefore, we examined the processing of procholecystokinin (proCCK) in the brain (neurons) and small intestine (endocrine cells) of fat/fat mice. In the brain, bioactive CCK was markedly reduced (7.9+/-1.0 pmol/g in fat/fat mice vs. 82.5+/-11.2 pmol/g in controls), but the concentration of the CPE substrate, glycylarginine-extended CCK, was elevated 105-fold. In contrast, the concentration of bioactive CCK in intestinal endocrine cells was unaffected. Endocrine cell processing was, nevertheless, altered with a 33-fold increase in glycyl-arginine-extended CCK. Interestingly, although total proCCK products were normal in the brain they were elevated 3-fold in the intestine, indicating that biosynthesis is upregulated in endocrine cells but not neurons to compensate for the processing defect. These results demonstrate that the CPE mutation differentially affects CCK processing in these two cell types. Intestinal CCK synthesis more closely resembles progastrin processing, suggesting the presence of an endocrine-specific biosynthetic regulatory mechanism not present in neurons.

Animals↗

PubMed2000

Targeting of membrane proteins to the regulated secretory pathway in anterior pituitary endocrine cells.

Unlike the neuroendocrine cell lines widely used to study trafficking of soluble and membrane proteins to secretory granules, the endocrine cells of the anterior pituitary are highly specialized for the production of mature secretory granules. Therefore, we investigated the trafficking of three membrane proteins in primary anterior pituitary endocrine cells. Peptidylglycine alpha-amidating monooxygenase (PAM), an integral membrane protein essential to the production of many bioactive peptides, is cleaved and enters the regulated secretory pathway even when expressed at levels 40-fold higher than endogenous levels. Myc-TMD/CD, a membrane protein lacking the lumenal, catalytic domains of PAM, is still stored in granules. Secretory granules are not the default pathway for all membrane proteins, because Tac accumulates on the surface of pituitary endocrine cells. Overexpression of PAM is accompanied by a diminution in its endoproteolytic cleavage and in its BaCl(2)-stimulated release from mature granules. Because internalized PAM/PAM-antibody complexes are returned to secretory granules, the endocytic machinery of the pituitary endocrine cells is not saturated. As in corticotrope tumor cells, expression of PAM or Myc-TMD/CD alters the organization of the actin cytoskeleton. PAM-mediated alterations in the cytoskeleton may limit maturation of PAM and storage in mature granules.

Actins↗

PubMed1982

Endocrine cells and melanin-containing cells in the anal canal epithelium.

The epithelium of the anal canal from 22 humans was studied in order to demonstrate the possible presence of endocrine cells and melanin-containing cells. Histochemical methods aimed at demonstrating reducing substances, biogenic amines, argyrophilia and melanin, were used. Enterochromaffin cells, and possibly other types of endocrine cells, were demonstrated above the dentate line both in colo-rectal type epithelium and in the anal transitional zone. Melanin-containing cells could also occasionally be found in the anal transitional zone. The presence of endocrine cells in the anal canal epithelium opens up the possibility that carcinoids can originate in this region. Further, the presence of melanin-containing cells might explain the occurrence of malignant melanomas arising above the dentate line.

Adenocarcinoma↗

PubMed1989

[Quantitative characteristics of various endocrine cells of the duodenal bulb in the pre-ulcer conditions and duodenal ulcer].

Endocrine cells of the duodenal bulb producing adrenalin, noradrenalin, serotonin, histamine and beta-endorphine were assayed in 12 patients with preulcer and 39 patients with duodenal ulcer. It is shown that preulcer was mainly characterized by hyperplasia of endocrine cells in the duodenal bulb mucosa, secreting adrenalin and noradrenalin in the presence of the deficiency of beta-endorphine-producing cells. The recurrent duodenal ulcer was associated with a dramatic fall in the number of catecholamine-containing endocrine cells in the duodenal bulb.

APUD Cells↗

PubMed1982

An immunocytochemical and electron-microscopical study of endocrine cells in the gut and pancreas of a stomachless teleost fish, Barbus conchonius (Cyprinidae).

Four immunoreactive endocrine cell types can be distinguished in the pancreatic islets of B. conchonius: insulin-producing B cells, somatostatin-producing A1 (= D) cells, glucagon-producing A2 cells and pancreatic polypeptide-producing PP cells. The principal islet of this species contains only a few PP cells, while many PP cells are present in the smaller islets. Except for the B cell all pancreatic endocrine cell types are also present in the pancreatic duct. At least six enteroendocrine cell types are present in the gut of B. conchonius: 1. a cell type (I) with small secretory granules, present throughout the intestine, and possibly involved in the regulation of gut motility; 2. a C-terminal gastrin immunoreactive cell, probably producing a caerulein-like peptide; these cells are located at the upper parts of the folds, especially in the proximal part of the intestinal bulb; 3. a met-enkephalin-immunoreactive cell, present throughout the first segment; 4. a glucagon-immunoreactive cell, which is rare in the first segment; 5. a PP-immunoreactive cell, mainly present in the first half of the first segment; 6. an immunoreactive cell, which cannot at present be specified, located in the intestinal bulb. The latter four cell types are mostly located in the basal parts of the folds, although some PP-immunoreactive cells can also be found in the upper parts. Most if not all enteroendocrine cells are of the open type. The possible functions of all enteroendocrine cell types are discussed.

Animals↗

PubMed1989

Differentiation of endocrine cells in chick allantoic epithelium combined with pancreatic mesenchyme.

Allantoic endoderm of 3-day chick embryos was combined with pancreatic mesenchyme of 5-day embryos and cultured as chorio-allantoic grafts for a total of 14 days. Recombinations of endoderm and mesenchyme of the pancreas and of the allantois served as controls. The usual types of endocrine cells differentiated in the pancreatic controls, none in the allantoic controls. In experimental grafts simple columnar epithelium with goblet cells and a sucrase-positive brush border developed; a few insulin cells and endocrine cells typical of the intestine differentiated. Hence allantoic endoderm has endocrine potentiality not realised in vivo, where its own mesenchyme may be inhibitory.

Allantois↗

PubMed1988

Expression of glycoprotein hormone alpha-subunit by endocrine cells of the oxyntic mucosa is associated with hypergastrinemia.

Previous studies have shown that hyperplastic endocrine cells of the oxyntic mucosa in patients with atrophic gastritis may express immunoreactivity for the alpha-subunit of human chorionic gonadotropin (alpha-HCG, common to all glycoprotein hormones). Since this endocrine proliferation is regarded as dependent on the trophic effect of the concomitant hypergastrinemia, the relation between immunohistochemical expression of alpha-HCG by oxyntic endocrine cells and serum levels of gastrin were investigated. The study was performed on endoscopic gastric biopsies of the oxyntic mucosa from 49 patients subdivided into the following groups: A) with histologically normal mucosa and normogastrinemia (22 cases), B) with atrophic gastritis and normogastrinemia (12 cases), C) with normal mucosa and hypergastrinemia (Zollinger-Ellison syndrome, retained antrum) (7 cases) and D) with atrophic gastritis and hypergastrinemia (with or without pernicious anemia) (8 cases). The alpha-HCG immunoreactive cells were found in all hypergastrinemic patients (groups C and D), regardless of the concomitant pathological condition of the mucosa. These cells accounted for 7.8% to 44.7% of the number of Grimelius argyrophil cells in consecutive serial sections. In contrast, alpha-HCG-containing cells were exceptional or absent in most normogastrinemic patients. Their number was sizable in only two cases of group A and three cases of group B, where it ranged from 2.5% to 14.8% of the number of argyrophil cells. It was concluded that expression of alpha-HCG is another feature of oxyntic endocrine cells associated with hypergastrinemia in addition to those previously recognized such as development of hyperplasia and/or carcinoid tumors.

Adolescent↗

PubMed1978

Endocrine cells in the gut of the ascidian Styela clava.

Ultrastructural studies have shown the presence of two types of granulated endocrine cell in the gut of Styela clava. Type I, which occurs in the stomach and intestine contains small irregular granules, each with a distinct halo. Type II, found only in the oesophagus contains larger rounded granules, often with little or no halo. The characteristics of these two cell types are compared with those of endocrine cells found in the digestive tracts of other protochordates and discussed with special reference to the evolution of gastrointestinal endocrine cells in vertebrates.

Animals↗

PubMed1987

Glycoprotein hormone alpha-chain-immunoreactive endocrine cells in prostate and cloacal-derived tissues.

All cloacal-derived tissues contain a similar endocrine cell population. Human chorionic gonadotropin (hCG)-like immunoreactivity has been reported in some prostatic endocrine cells. On the other hand, immunoreactivity to alpha-hCG is well known to occur in a variety of extraprostatic endocrine elements. Most cloacal-derived tissues were tested with a panel of monoclonal antibodies against hCG and subunits. The previously described hCG-like positivity was found to be exclusively related to the free alpha-subunit of hCG. Moreover, alpha-chain immunoreactivity was more broadly distributed in most cloacal-derived tissues, including those from the anal canal. In the anal canal, alpha-chain was an excellent marker of the anal transitional zone. alpha-Chain-immunoreactive endocrine cells were normal and nonneoplastic constituents of these tissues; they corresponded to a subpopulation of serotonin cells. In addition, certain prostatic argyrophil cell carcinomas might be exclusively alpha-subunit producing.

Calcitonin↗

PubMed1978

Influence of autolysis on rat gastric endocrine cells. Histochemical and electron microscopical study.

In the present study histochemical parameters of the rat gastric endocrine cells were followed up in the course of 24-h autolysis, and their ultrastructure was studied during autolysis lasting for 60 min. The autolysis occurred at 37 degrees C. In the light microscope, with the histochemical methods applied, only EC, ECL and G cells could be identified during the one-hour autolysis. With the autolysis proceeding for 6 and 12 h, only argyrophil method according to Grimelius (1968) enabled visualization of gastric argyrophilic cells. After 24 h of autolysis, none of the methods applied (not even the Grimelius method) proved to be adequate for successful demonstration of the gastric endocrine cells. In the course of 60-min autolysis, electron microscopic examination provided identification of the EC, ECL, AL, D1, and G cells with the characteristical ultrastructural appearance of granules. The granules of the endocrine cells (G cells included) were found to be considerably resistant to autolysis. The effect of 60-min autolysis did not induce granule "emiocytosis" or dissolution of granule content. Autolysis exceeding five minutes resulted in damage of the mitochondria of different degrees and in dilatation of the profiles of endoplasmic reticulum (particularly in G and AL cells). The results obtained in the present study demonstrate the feasibility of in vitro experimental stimulation since the endocrine granules have proved to be resistant to the effects of simultaneously developing autolysis.

Animals↗

PubMed1996

Peptide YY expression is an early event in colonic endocrine cell differentiation: evidence from normal and transgenic mice.

The hormone peptide YY is produced by endocrine cells in the pancreas, ileum and colon. We have previously shown that peptide YY is coexpressed in all four islet cell types in the murine pancreas when they first appear, suggesting a common peptide YY-producing progenitor. In the colon, peptide YY has been frequently identified in glucagon-expressing L-type endocrine cells. Characterization of colonic endocrine tumors in transgenic mice expressing simian virus 40 large T antigen under the control of the peptide YY gene 5' flanking region revealed tumor cells producing not only peptide YY and glucagon, but also neurotensin, cholecystokinin, substance P, serotonin, secretin, and gastrin. This suggested that multiple enteroendocrine lineages were related to peptide YY-producing cells. Subsequent examination of the ontogeny of colonic endocrine differentiation in nontransgenic mice revealed that peptide YY was the first hormone to appear during development, at embryonic day 15.5. Between embryonic days 16.5 and 18.5, cells expressing glucagon, cholecystokinin, substance P, serotonin, secretin, neurotensin, gastrin and somatostatin first appeared and peptide YY was coexpressed in each cell type at this time. Peptide YY coexpression continued in a significant fraction of most enteroendocrine cell types throughout fetal and postnatal development and into adulthood, with the exception of serotonin-producing cells. This latter population of cells expanded dramatically after birth with rare coexpression of peptide YY. These studies indicate that expression of peptide YY is an early event in colonic endocrine differentiation and support the existence of a common progenitor for all endocrine cells in the colon.

Animals↗

PubMed1983

An immunohistochemical survey of endocrine cells and nerves in the proximal small intestine of the platypus, Ornithorhynchus anatinus.

The relative frequencies of endocrine cells and peptidergic nerve elements in the proximal small intestine of the adult platypus were studied by immunohistochemistry. Six kinds of endocrine cells - serotonin (5-HT)-, somatostatin-, gastrin-, motilin-, cholecystokinin (CCK)- and bovine pancreatic polypeptide (BPP)-immunoreactive cells - were identified in this study. These endocrine cells were found most frequently in the intestinal glands, in moderate numbers in the tubular ducts and were infrequent in the surface folds. 5-HT-immunoreactive cells were most numerous, somatostatin-, gastrin-, motilin- and BPP-immunoreactive cells were moderately numerous, whereas CCK-immunoreactive cells were rare. Five kinds of neuropeptides: substance P, vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP), somatostatin and leu-enkephalin, were detected in the intramural nerve elements. Substance P-, VIP- and GRP-immunoreactive nerve fibers were found most frequently in the lamina propria mucosae of the surface folds. The relationships between the possible functions of the peptides and amine detected in this study as well as the characteristic structure of the digestive tract of the adult platypus are discussed.

Animals↗

PubMed1991

Immunocytochemical and ultrastructural characterization of endocrine cells in chicken proventriculus.

The endocrine cells of the chicken proventriculus were investigated immunocytochemically, using the peroxidase-antiperoxidase technique on paraffin and semithin sections for light microscopy, and immunogold staining in osmium-fixed material for electron microscopy. The fixation procedure also allowed a detailed ultrastructural investigation. Twenty-three antisera were tested and 7 immunoreactive cell-types were identified: D-cells containing somatostatin-like peptide; EG-cells immunoreactive to anti-glucagon, anti-GLP1 and anti-neurotensin; NT-cells labelled only with anti-neurotensin; BN-cells containing bombesin-like material; ENK-cells showing met-enkephalin immunoreactivity; EC-cells reactive to anti-serotonin; and APP-cells positive to anti-avian pancreatic polypeptide. In addition, enterochromaffin-like (ECL) cells, were also detected by electron microscopy. The presence of ENK-cells and the ultrastructure of these and NT-cells are described for the first time in chicken proventriculus, and glucagon. GLP1 and neurotensin are shown to be colocalized in the EG-cells.

Animals↗