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PubMed1987

The effect of pancreatic mesenchyme on the differentiation of endocrine cells from gastric endoderm.

To determine whether mesenchyme plays a part in the differentiation of gut endocrine cells, proventricular endoderm from 4- to 5-day chick or quail embryos was associated with mesenchyme from the dorsal pancreatic bud of chick embryos of the same age. The combinations were grown on the chorioallantoic membranes of host chick embryos until they reached a total incubation age of 21 days. Proventricular or pancreatic endoderm of the appropriate age and species reassociated with its own mesenchyme provided the controls. Morphogenesis in the experimental grafts corresponded closely to that in proventricular controls, i.e. the pancreatic mesenchyme supported the development of proventricular glands from proventricular endoderm. Insulin, glucagon and somatostatin cells and cells with pancreatic polypeptide-like immunoreactivity differentiated in the pancreatic controls. The latter three endocrine cell types, together with neurotensin and bombesin/gastrin-releasing polypeptide (GRP) cells, developed in proventricular controls and experimental grafts. The proportions of the major types common to proventriculus and pancreas (somatostatin and glucagon cells) were in general similar when experimental grafts were compared with proventricular controls but different when experimental and pancreatic control grafts were compared. Hence pancreatic mesenchyme did not materially affect the proportions of these three cell types in experimental grafts, induced no specific pancreatic (insulin) cell type and allowed the differentiation of the characteristic proventricular endocrine cell types, neurotensin and bombesin/GRP cells. However, an important finding was a significant reduction in the proportion of bombesin/GRP cells, attributable in part to a decrease in their number and in part to an increase in the numbers of endocrine cells of the other types. This indicates that mesenchyme may well play a part in determining the regional specificity of populations of gut endocrine cells.

Animals↗

PubMed1984

Coexistence of peptide YY and glicentin immunoreactivity in endocrine cells of the gut.

Endocrine cells containing peptide YY (PYY) were numerous in the rectum, colon and ileum and few in the duodenum and jejunum of rat, pig and man. No immunoreactive cells could be detected in the pancreas and stomach. Coexistence of PYY and glicentin was revealed by sequential staining of the same section and by staining consecutive semi-thin sections. Since the PYY sequence is not contained in the glucagon/glicentin precursor molecule the results suggest that the PYY cell in the gut expresses two different genes coding for regulatory peptides of two different families.

Animals↗

PubMed1992

Can a non-gut mesenchyme support differentiation of gut endocrine cells?

This experiment was designed to find out if endoderm lacks an intrinsic ability to give rise to gut endocrine cells, and, if not, whether differentiation of endocrine cells can be supported by mesenchyme from a source outside the digestive tract. Heterospecific combinations of proventricular endoderm and flank mesenchyme from chick and quail embryos at 3.25-4 days of incubation were grown as chorio-allantoic grafts to a final incubation age of 21 days. Re-associated proventricular endoderm and mesenchyme served as controls. The proventricular endoderm induced some smooth muscle in the flank mesenchyme but the latter did not support as advanced glandular morphogenesis as did proventricular mesenchyme. Nevertheless, endocrine cells differentiated in experimental as in control grafts and at similar frequencies. The various types were distinguished immunocytochemically by their contained peptides; the range of types found was specific for the proventriculus. Hence it is concluded not only that the particular non-gut mesenchyme used does support differentiation of gut endocrine cells, but also that the determination of the progenitors of endocrine cells, and the selection of the range of types destined to differentiate in a particular part of the digestive tract under normal circumstances, occurs early in development--before 3.25 days of incubation in the case of the proventriculus.

Animals↗

PubMed1997

An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei).

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.

Animals↗

PubMed1990

Unusual proliferation of the pancreatic endocrine cells in adults, suggestive of islet cell metaplasia.

We present two adult autopsy cases with malignancy, in which unusual proliferation of the pancreatic endocrine cells was observed. Histopathological examination revealed extensive proliferation of the pancreatic endocrine cells throughout the pancreata in both cases. The islets of the pancreas were enlarged with irregular contours. An admixture of the islet cells, acinar cells and ductular epithelial cells was also observed. Immunohistochemically, these islets were composed of the endocrine cells of various types, i.e. A-, B-, D- and PP-cells, and they showed a predominance of PP-cells. Clinically, endocrine hyperfunction of the pancreas was not detected in either cases. Although this histological change may be described as endocrine cell hyperplasia or dysplasia, the close connection of the islet cells, acinar cells and ductular epithelial cells might rather suggest metaplastic change of the acinar or ductular cells into the islet cells under unknown stimuli.

Carcinoma, Squamous Cell↗

PubMed1989

Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells.

In this immunocytochemical study, we have analyzed the developmental profile and phenotypic expression of the endocrine cell antigens chromogranin, 5-hydroxytryptamine, gastrin/cholecystokinin, cholecystokinin (9-20), somatostatin, somatostatin 28 (1-14), somatostatin cryptic peptide, glucagon, glucagonlike peptides 1 and 2, glicentin, peptide YY, glucose-dependent insulinotropic peptide, secretin, neurotensin, and substance P in human fetal stomach and intestine. All currently identifiable endocrine cell types were detected by 10 wk of gestation. Immunostaining for the endocrine cell marker chromogranin revealed abundant endocrine cells in the earliest specimens (8 wk of gestation) with a relatively higher frequency in both proximal duodenum and distal colon/rectum compared with other areas. Quantification of endocrine cells showed an increase with age that was roughly parallel to the growth of the gut as a whole. These studies show that the diversity of the endocrine component of the gut appears to be established by 10 wk of gestation and that gut activity is preceded by the development of a fully differentiated endocrine component, which may subserve or even initiate the onset of functional maturity.

Antibodies, Monoclonal↗

PubMed2006

Multiple endocrine neoplasia type 1 (MEN1): loss of one MEN1 allele in tumors and monohormonal endocrine cell clusters but not in islet hyperplasia of the pancreas.

CONTEXT: The occurrence of multiple small pancreatic endocrine tumors in patients suffering from multiple endocrine neoplasia type 1 (MEN1) represents a unique possibility to study early neoplasms and their potential precursor lesions. To date, it is unknown whether small islet-like endocrine cell clusters found in MEN1 patients are neoplastic or rather hyperplastic. It is also unclear whether microadenomas develop from islets. DESIGN: We hypothesized that monohormonal endocrine cell clusters observed in MEN1 patients are small neoplasms with loss of heterozygosity of the MEN1 locus. Using a technique combining fluorescence in situ hybridization of the MEN1 locus and the centromeric region of chromosome 11q with hormone immunostaining, we examined resection specimens from four MEN1 patients. We focused our investigations on the following: 1) typical microadenomas; 2) monohormonal endocrine cell clusters; 3) endocrine and exocrine structures entrapped in microadenomas; and 4) morphologically normal islets. RESULTS: Loss of one MEN1 allele was found in all 27 microadenomas and 19 of 20 (95%) monohormonal endocrine cell clusters. By contrast, it was absent in islets and ductal or acinar structures. Our results indicate that monohormonal endocrine cell clusters represent a minute form of microadenomas. CONCLUSION: The frequent presence of single nonneoplastic insulin cells in microadenomas and the occurrence of microadenomas in islets suggest an islet origin of microadenomas. Islet hyperplasia does not seem to be an obligatory stage in pancreatic MEN1-associated tumor development.

Adult↗

PubMed2004

Changes of gastrointestinal argyrophil endocrine cells in the osteoporotic SD rats induced by ovariectomy.

The regional distributions and frequencies of argyrophil endocrine cells in gastrointestinal (GI) tract of osteoporotic Sprague-Dawley rat induced by ovariectomy were studied using Grimelius silver stain. The experimental animals were divided into two groups, one is non-ovariectomized group (Sham) and the other is ovariectomized group (OVX). Samples were collected from each part of GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 10th week after ovariectomy or sham operation. In this study, argyrophil cells were detected throughout the entire GI tract with various frequencies regardless of ovariectomy. Most of these argyrophil cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found occasionally in gastric and/or intestinal gland regions. The regional distributions of GI argyrophil endocrine cells in OVX were similar to those of Sham. However, significant decreases of argyrophil cells were detected in OVX compared to those of Sham except for the pylorus, jejunum and cecum. In pylorus and jejunum, argyrophil cells in OVX dramatically decreased compared to those of Sham but significances were not recorded. In addition, argyrophil cells in cecum of OVX showed similar frequency compared to that of Sham. The endocrine cells are the anatomical units responsible for the production of gut hormones that regulate gut motility and digestion including absorption, and a change in their density would reflect the change in the capacity of producing these hormones and regulating gut motility and digestion. Ovariectomy induced severe quantitative changes of GI argyrophil endocrine cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis.

Animals↗

PubMed2000

Regulating effect of epithalone on gastric endocrine cells in pinealectomized rats.

Endocrine cells in the stomach of pinealectomized rats after injection of epithalone (pineal gland peptide) were studied by immunohistochemical tests, morphometry, and image analysis microscopic images. A functional relationship was found between the pineal gland and stomach, which is regulated by peptides produced by the pineal gland.

Animals↗

PubMed1990

Quantitative ultrastructure of endocrine cells of oxyntic mucosa in Zollinger-Ellison syndrome. Correspondence with light microscopic findings.

The endocrine cells of the oxyntic mucosa of five patients with longstanding Zollinger-Ellison syndrome were quantitatively investigated with electron microscopy and two light microscopic methods (Grimelius and immunostaining for chromogranin A). Ultrastructurally, the volume density of endocrine cells was 3.2% +/- 1.1% of the mucosal epithelial component, a 168% increase (P less than 0.001) over the value found in normal subjects. Of the six endocrine cell types of human oxyntic mucosa, only enterochromaffinlike cells increased in cell density (65% +/- 15% of the total endocrine cell mass), size, and number of cell profiles per unit area. The enterochromaffinlike cells also underwent morphological changes of secretory granules with a decrease in vacuolated forms, increase in elongated profiles, and appearance of granules with a punctate structure of the core. The latter variety of granules was previously observed only in carcinoid tumors of the oxyntic mucosa and is possibly related to the enterochromaffinlike cell hyperplasia-neoplasia sequence seen in hypergastrinemic patients. A positive relationship was found between endocrine cell densities evaluated ultrastructurally and with chromogranin A immunostaining. It is concluded that in Zollinger-Ellison syndrome, the trophic effects induced by longstanding hypergastrinemia are strictly selective for enterochromaffinlike cells and are associated with ultrastructural features typical for enterochromaffinlike cell tumors.

Adult↗

PubMed1978

Ultrastructural and cytochemical studies on the cytodifferentiation of duodenal endocrine cells.

The development of cytodifferentiation of endocrine cells that produce the gastrointestinal hormones gastrin, cholecystokinin and secretin have been studied by a combined fluorescence-cytochemical, immunocytochemical and ultrastructural approach. The results show that, during development, several ultrastructurally distinct cell types exhibit COOH-terminal gastrin and cholecystokinin immunoreactivity. Furthermore, some cells simultaneously contain both gastrin- and cholecystokinin-specific antigenic determinants. Studies on the time course of development of gastrin and cholecystokinin cells, together with the above-mentioned data, suggest that gastrin cells may be converted into cholecystokinin cells in development. During this period, gastrin, cholecystokinin and secretin cells store the biogenic monoamine, 5-hydroxytryptamine a feature not displayed by the adult counter-parts of these cells. In the adult duodenum, characteristic enterochromaffin (EC) cells store 5-hydroxytryptamin for which, evidence for a possible hormonal role has been presented. Taken together, our data indicate that the differentiation of duodenal endocrine cells occurs in distinct steps, each involving a restriction in the biosynthetic repertoire of the cell.

Animals↗

PubMed1978

Endocrine cells in the pyloric region of the Japanese quail (Coturnix coturnix japonica).

The endocrine cells of the pyloric region of the Japanese quail have been studied by light and electron microscopy. The quail pyloric region is a narrow circular zone (about 2 mm in width) between the gizzard and the duodenum. The endocrine cells are concentrated in this region, and they are represented by argyrophil cells. At least five types of endocrine cells are identified in this region by electron microscopy. Type I cells are characterized by having round and large granules (350--550 nm in diameter) whose contents are high to moderate in electron density. Type II cells are characterized by their round and medium-sized granules (250--350 nm) which possess a dense core and a clear halo. Type III cells are characterized by the presence of round and small-cored granules (150--250 nm). Type IV cells contain round and large granules (350--550 nm) of high to low electron density. Type V cells are identified by the occurrence of microfilaments and polymorphous granules of high electron density. All five cell types are recognized as open type cells. The type I, II and III cells are located mainly in the lower half portion of pyloric glands, and the other cell types are located only in the upper half portion of the glands. The type I and II cells are found much more frequently than other cell types. The relationships between the endocrine cells in the quail pyloric region and those of the mammalian digestive tracts were discussed.

Animals↗

PubMed1990

An immunohistochemical study on the distribution of endocrine cells in the gastrointestinal tract of the musk shrew, Suncus murinus.

The endocrine cells in the gastrointestinal tract of the musk shrew were studied immunohistochemically. Eleven kinds of endocrine cells, immunoreactive for serotonin, somatostatin, gastrin, cholecistokinin, gastric inhibitory polypeptide, motilin, secretin, neurotensin, pancreatic glucagon, enteroglucagon and bovine pancreatic polypeptide, were revealed. In the stomach, serotonin-, somatostatin-, gastrin-, pancreatic glucagon- and enteroglucagon-immunoreactive cells were detected. The first three types of cells predominated and were more abundant in the pyloric glands than in the other stomach regions. In the small intestine, all types of endocrine cells were found, each having different distributions and relative frequencies. In the large intestine, 10 types of endocrine cells except cholecystokinin-immunoreactive cells were detected. Serotonin- and bovine pancreatic polypeptide-immunoreactive cells were more numerous in the large intestine than in the small intestine.

Animals↗

PubMed1993

Role of growth factors in pancreatic endocrine cells. Growth and differentiation.

Although previously thought to arise from neural ectoderm, the endocrine cells of the gastrointestinal system are now believed to derive from endoderm. The role of different growth factors in initiation of endocrine cell growth, commitment of the cells to a particular growth pathway, and the initiation and maintenance of tumor growth and remission remains unclear. This article briefly reviews factors controlling cell growth and differentiation of gastrointestinal endocrine cells and presents data on new candidate growth factors pertinent to the authors' model of induction of endocrine cell differentiation in the pancreas.

Cell Differentiation↗

PubMed1977

Immunohistochemical localization of neurotensin in endocrine cells of the gut.

Endocrine cells displaying neurotensin immunoreactivity are found scattered in the jejuno-ileum of all mammals studied, including man. They are rather scarce in rat, guinea pig, rabbit and pig and fairly numerous in cat, dog and man. In most mammals the neurotensin cells predominate on the villi. Only in the dog are they more numerous in the crypts. In the chicken, neurotensin cells occur all along the intestinal tract. They are particularly numerous in the zone that joins the gizzard with the duodenum. The ontogeny of the neurotensin cells in the gut was studied in rats and chickens. In the rat, the cells are first observed in the jejuno-ileum immediately before birth. The adult frequency is reached 4-5 days later. In the chicken, neurotensin cells first appear in the colon in the 18 day old embryo and in the small intestine two days later (i.e. one or two days before hatching). A few days after hatching, the gut has achieved the adult number of neurotensin cells per unit area.

Age Factors↗

PubMed1975

Immunochemical studies of the endocrine cells of the gastrointestinal tract. II An immunoperoxide technique for the localization of secretin containing cells in human duodenum.

Endocrine cells containing secretin have been identified in the epithelium lining human duodenum by direct and indirect immunoperoxidase techniques using immune sera raised against pur natural secretin. The techniques were applied to sections of carbodiimide-fixed tissue embedded in polyethylene glycol. Some sections, stained by a modified indirect technique, were processed for electron microscopy; secretin-containing granules were present by ultrastructural preservation was too poor to be of value. The potential advantages of a peroxidase technique over fluorescein-coniugated antisera are discussed.

Carbodiimides↗

PubMed1994

[The biological significance of endocrine cells in pancreatic carcinoma].

Endocrine cells (EC) were found in 19 out of 42 cases of the pancreas carcinoma (42.5%). Among them, 4 cases had a positive rate of EC more than 50%. The positive rate of EC in the well differentiated carcinomas (5/20) was lower than that of the poorly-differentiated ones (12/19) or mucinous carcinoma (2/2), and the positive rate in histologic grade I cases (5/18) was significantly lower than that of the grade III cases (7/8). The number of mast cells infiltrating in the matrix in EC positive cases was significantly higher than that of the negative ones. The positive rate of EC in the cases with metastasis (8/14) was higher than that of the non-metastasis cases (7/21). Immunocytochemical staining showed that GN (8), SS(4), HCG(5), CK(12), EMA(13) and CEA(9) were positive in 19 EC positive cases.

Adenocarcinoma↗

PubMed2000

Liver transplantation restores endocrine cells in patients with familial amyloidotic polyneuropathy.

BACKGROUND: The aim of this study was to investigate familial amyloidotic polyneuropathy, Portuguese type patients' endocrine cell content in the stomach and duodenum before and after liver transplantation, and to relate the findings to the patients' gastrointestinal disturbances. METHODS: Ten liver-transplanted familial amyloidotic polyneuropathy, Portuguese type patients and 10 healthy controls were seen. Endocrine cells were identified by immunohistochemistry and quantified with computerized image analysis. The activity of the cells was appraised by measurements of the cell secretory index and nuclear area. Clinical symptoms were obtained from the patients' medical records. RESULTS: After transplantation, a significant increase of several endocrine cell types were noted, and the pretransplant depletion of several types of endocrine cells disappeared. For no type of endocrine cell was any difference compared with controls noted after transplantation. There was no significant decrease of the amount of amyloid in the biopsies after liver transplantation. The patients' symptoms remained generally unchanged after transplantation, although a substantial time lapse between pretransplant evaluation and transplantation was present. CONCLUSIONS: Liver transplantation restores the endocrine cells in the upper part of the gastrointestinal tract. The restoration was not correlated with an improvement of the patients' symptoms. No decrease of the amyloid deposits was noted.

Adult↗