Regeneration of endocrine cells in the stomach

A mucosal defect was produced by cryosurgery in the antral and the fundic wall of the rat stomach, and regeneration of gastric endocrine cells was studied 50, 100 and 200 days after operation. Fifty days after the operation, the mucosal defect was completely covered with regenerated epithelium. The regenerated mucosa both in the antral and in the fundic region consisted of mucinous glandular structures. The regenerated mucosa in the corpus remained pseudopyloric in type even 200 days after operation. Regardless of the time after operation, regeneration of endocrine cells was always observed. We could identify G cells and EC cells in the regenerated mucosa of the antrum, and EC cells, A cells and AL cells in the regenerated mucosa of the corpus, respectively. By electron microscopy, endocrine-exocrine cells were frequently encountered. These cells had two different types of intra-cytoplasmic granules; one was an endocrine-specific, small electron-dense granule, and the other a large, lucent mucin droplet-like granule. These findings indicate that the endocrine cells of the stomach are formed from endodermal precursor cells.     

Histamine in endocrine cells in the stomach

Summary Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions (paracrine appearance), running close to the base of the oxyntico-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a paracrine appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedge-hog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man. In the oxyntic mucosa of the latter three species mast cells sometimes seemed to have an intraepithelial localization which made their distinction from endocrine cells difficult. In newborn cats (1–3 days old) in human foetuses (17–24 weeks gestational age) mast cells were relatively few in the gastric mucosa and the histamine-containing endocrine cells were easier to demonstrate as a consequence. Patients with achlorhydria (and pernicious anemia) or suffering from hypergastrinemia due to gastrinoma had a greatly increased number of histamine-storing endocrine cells in the oxyntic mucosa compared with normal individuals.     

Enterochromaffin cells as the endocrine source of gastrointestinal Substance P

Summary Immunoreactive Substance P is localized in the intramural neural plexuses of mammalian intestine, and in endocrine cells in the intestinal mucosa which have now been identified as enterochromaffin (EC). The presence of a neurotransmitter peptide in these cells favours the hypothesis of their neuroectodermal origin.On leave from the Department of Pathology, University of Basle; in receipt of a grant from the Swiss Academy of Medical Sciences     

Microscopic organization of epithelial endocrine cells of the gastrointestinal tract mucosa in lower vertebrates. I. Epithelial endocrine cells of the stomach of the common frog

The quantity, histotopography and submicroscopic organization of endocrine cells in various mucosal epithelium sections of frog were studied using light and electron microscopy. It is shown that the majority of endocrine cells per square millimetre is located in the proximal part of the stomach. Eight types of endocrine cells depending on the submicroscopic structure of secretory granules are defined.     

Exocytotic release of vasoactive intestinal polypeptide and serotonin from mucosal nerve fibres and endocrine cells of the intestine of the goldfish (Carassius auratus) and the tilapia (Oreochromis mossambicus): an ultrastructural study

In earlier studies we determined the effect, presence and ultrastructure of vasoactive intestinal polypeptide (VIP) and 5- hydroxytryptamine (5-HT)-containing nerve fibres in the tilapia and goldfish intestinal mucosa. 5-HT-labelled varicosities were found close to the epithelial cells; however, synaptic membrane specializations have never been observed. VIP-like immunoreactive nerve fibres appear to be located less frequently close to the goldfish epithelium, as in the tilapia intestine, in which the distance between the VIP- or 5-HT-labelled varicosities and the epithelial cells was also rather large (more than 2 μm). To establish a possible role of VIP and 5-HT as neurotransmitters involved in the regulation of fish intestinal epithelium, both electron microscopical and immunoelectron microscopical methods were used to visualize the release of 5-HT and VIP from nerve fibres. We found exocytoses from VIP-ergic and serotonergic varicosities in the muscle layers of both fish. Directly underneath the intestinal epithelium of the goldfish, it was demonstrated that 5-HT could be released from scarce varicosities. The release of 5-HT in the tilapia intestinal mucosa could only be observed from endocrine cells     

Exocytotic release of vasoactive intestinal polypeptide and serotonin from mucosal nerve fibres and endocrine cells of the intestine of the goldfish (Carassius auratus) and the tilapia (Oreochromis mossambicus): an ultrastructural study

In earlier studies we determined the effect, presence and ultrastructure of vasoactive intestinal polypeptide (VIP) and 5- hydroxytryptamine (5-HT)-containing nerve fibres in the tilapia and goldfish intestinal mucosa. 5-HT-labelled varicosities were found close to the epithelial cells; however, synaptic membrane specializations have never been observed. VIP-like immunoreactive nerve fibres appear to be located less frequently close to the goldfish epithelium, as in the tilapia intestine, in which the distance between the VIP- or 5-HT-labelled varicosities and the epithelial cells was also rather large (more than 2 μm). To establish a possible role of VIP and 5-HT as neurotransmitters involved in the regulation of fish intestinal epithelium, both electron microscopical and immunoelectron microscopical methods were used to visualize the release of 5-HT and VIP from nerve fibres. We found exocytoses from VIP-ergic and serotonergic varicosities in the muscle layers of both fish. Directly underneath the intestinal epithelium of the goldfish, it was demonstrated that 5-HT could be released from scarce varicosities. The release of 5-HT in the tilapia intestinal mucosa could only be observed from endocrine cells     

Ultrastructural characteristics of endocrine and glandular gastric cells

Electron microscopy of human gastric mucosa has demonstrated that the endocrine cells are closely and specifically related to the adjacent glandular cells and the basal membrane. Cytoplasmic strands of the adjacent cells surround the endocrine cells and their projections, probably, regulating their secretion. The above outlined relations are considered a structural basis for complex regulatory endocrine and paracrine functions of the gastric endocrine cells.     

Topology of chromogranins in secretory granules of endocrine cells.

Chromogranins A and B are glycoproteins originally detected in the adrenal medulla. These proteins are also present in a variety of neuroendocrine cells. The subcellular distribution of the chromogranins, and particularly their intra-granular topology are of special interest with respect to their putative functions. Endocrine cells of the guinea pig adrenal medulla, pancreas and gastric mucosa were investigated immunoelectron microscopically for the subcellular distribution of both chromogranins. Out of 13 established endocrine cell types in all locations, only two endocrine cell types showed immunoreactivity for both chromogranin A and B, and eight endocrine cell types showed immunoreactivities only for chromogranin A. These immunoreactivities varied inter-cellularly. Three endocrine cell types were unreactive for the chromogranins. Moreover, some hormonally non-identified endocrine cells in the pancreas and the gastric mucosa also contained chromogranin A immunoreactivities. Subcellularly, chromogranin A or B were confined to secretory granules. In most endocrine cells, the secretory granules showed chromogranin immunoreactivities of varying densities. Furthermore, the intra-granular topology of chromogranin A or B in the secretory granules varied considerably: in some endocrine cell types, i.e. chromaffin-, gastrin- and enterochromaffin-like-cells, chromogranin A immunoreactivity was localized in the perigranular and/or dense core region of the secretory granules; in others, i.e. insulin-, pancreatic polypeptide- and bovine adrenal medulla dodecapeptide-cells, it was present preferentially in the electron-opaque centre of the secretory granules; chromogranin B immunoreactivity was localized preferentially in the perigranular region of the secretory granules of chromaffin cells and gastrin-cells. The inter-cellular and inter-granular variations of chromogranin A and B immunoreactivities point to differences in biosynthesis or processing of the chromogranins among endocrine cells and their secretory granules.     

The endocrine cells of the rectum of adult ox.

In order to identify the endocrine cell types in various parts of the Ruminant gut, we have applied ultrastructural, both morphological and cytochemical, techniques, in parallel to the histochemical ones, to study the rectal mucosa of the adult Ox. In these studies we show that: "EC" cells, of the intestinal type, contain predominantly pleiomorphic granules, which are very electron dense and heavily reactive to "Masson" and "Grimelius" methods; "L" cells are recognizable by their numerous granules, which are fairly homogeneous in shape and osmiophilia. They do not react with "Masson" and are weak or negative to Grimelius s reaction. These granules occur near to others that are less dense, unreactive to "Masson", and that contain an argyrophilic matrix, with an eccentric electron dense core, which does not react with silver; "F-like" cells contain granules which are variable in shape, size and osmiophilia. They are unreactive to "Masson" and weak or unreactive to Grimelius silver; "H" cells contain few, small and uniformly osmiophilic granules. These are unreactive to "Masson" and uniformly reactive to "Grimelius". Our data suggest that the morphology, frequency and distribution of the cell types we have identified in the mucosa of the bovine rectum correspond with those reported in large intestine and rectum of Monogastrics, as by other authors described.     

NCI-H716 cells as a model for endocrine differentiation in colorectal cancer.

In colonic neoplasms, endocrine differentiation is encountered not only in carcinoid tumors but also in adenocarcinomas, where endocrine cells may represent a distinct line of differentiation in the tumor. The significance of endocrine differentiation in colorectal cancer is not well established, partly because of the paucity of tumor cell lines which can serve as a model for studying endocrine differentiation. In this report we describe the properties of NCI-H716 cells, a cell line derived from a poorly differentiated adenocarcinoma of the caecum, under various in vitro conditions and as xenografts in athymic mice. Phenotypical properties were immunohistochemically assessed using a panel of differentiation related antibodies, and also by Northern blot analysis and by electron microscopy. Receptors for biogenic amines and peptide hormones were analyzed by ligand binding assay. These studies show that: 1. NCI-H716 cells can be undifferentiated, or show endocrine, mucin-producing or "amphicrine" properties. 2. Endocrine differentiation of NCI-H716 cells preferentially occurs in xenografts in athymic mice, which suggests that mesenchymal elements induce endocrine differentiation. 3. NCI-H716 cells express large amounts of high affinity receptors for gastrin, serotonin and somatostatin and these substances can regulate growth. Thus, NCI-H716 cells form a suitable model for the study of endocrine differentiation in intestinal epithelium and of auto- or paracrine growth regulation in intestinal neoplasia.     

Immunohistochemical studies on peptide- and amine-containing endocrine cells and nerves in the gut and the rectal gland of the ratfish Chimaera monstrosa

Summary The occurrence and distribution of endocrine cells and nerves were immunohistochemically demonstrated in the gut and rectal gland of the ratfish Chimaera monstrosa (Holocephala). The epithelium of the gut mucosa revealed open-type endocrine cells exhibiting immunoreactivity for serotonin (5HT), gastrin/cholecystokinin (CCK), pancreatic polypeptide (PP)/FMRFamide, somatostatin, glucagon, substance P or gastrin-releasing peptide (GRP). The rectum contained a large number of closed-type endocrine cells in the basal layer of its stratified epithelium; the majority contained 5HT- and GRP-like immunoreactivity in the same cytoplasm, whereas others were immunoreactive for substance P. The rectal gland revealed closed-type endocrine cells located in the collecting duct epithelium. Most of these contained substance P-like immunoreactivity, although some reacted either to antibody against somatostatin or against 5HT. Four types of nerves were identified in the gut and the rectal gland. The nerve cells and fibers that were immunoreactive for vasoactive intestinal peptide (VIP) and GRP formed dense plexuses in the lamina propria, submucosa and muscular layer of the gut and rectal gland. A sparse network of gastrin- and 5HT-immunoreactive nerve fibers was found in the mucosa and the muscular layer of the gut. The present study demonstrated for the first time the occurrence of the closed-type endocrine cells in the mucosa of the rectum and rectal gland of the ratfish. These abundant cells presumably secrete 5HT and/or peptides in response to mechanical stimuli in the gut and the rectal gland. The peptide-containing nerves may be involved in the regulation of secretion by the rectal gland.     

A mixed pattern of endocrine cells in metaplastic Barrett's oesophagus. Evidence that the epithelium derives from a pluripotential stem cell

In order to characterize the differentiation of endocrine cells present in Barrett's oesophagus and to determine if they express a single or multiple hormonal pattern, endoscopic biopsies were taken from both the lesion and the fundus of 45 patients and studied at the light microscopical level. Conventional histology revealed three different epithelial patterns: gastric atrophic fundic, intestinal and junctional. A mixture of these patterns was present in 28 cases (62%) and the single type was identified in 17 cases (38%). The use of three silver staining methods and antibodies to human chromogranins allowed us to identify numerous endocrine cells in all but 1 case. Eleven sera against all the most common hormones stored in the endocrine cells of the gut were used to identify the main products of the cells. The following immunoreactivities were identified: 5-hydroxytryptamine (5-HT) (in 75% of the studied cases), somatostatin (87%), motilin (31%), pancreatic polypeptide (PP) (20%), glucose-dependent insulinotropic polypeptide (20%), gastrin (15%), glucagon (15%), peptide tyrosine tyrosine (13%), secretin (7%) and neurotensin (2%). No cholecystokinin-immunoreactive cells were identified. Our results indicated that, in Barrett's epithelium, both gastric and intestinal endocrine cells differentiate, in accordance with the variability of differentiation in the non-endocrine cells present in the different types of columnar epithelium. These findings provide support for the conclusion that Barrett's epithelium arises from a pluripotential stem cell capable of both gastric and intestinal differentiation.     

Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies

Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions ("paracrine" appearance), running close to the base of the oxyntic-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a "paracrine" appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedgehog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man.(ABSTRACT TRUNCATED AT 400 WORDS)     

A mixed pattern of endocrine cells in metaplastic Barrett's oesophagus

Summary In order to characterize the differentiation of endocrine cells present in barrett's oesophagus and to determine if they express a single or multiple hormonal pattern, endoscopic biopsies were taken from both the lesion and the fundus of 45 patients and studied at the light microscopical level. Conventional histology revealed three different epithelial patterns: gastric atrophic fundic, intestinal and junctional. A mixture of these patterns was present in 28 cases (62%) and the single type was identified in 17 cases (38%). The use of three silver staining methods and antibodies to human chromogranins allowed us to identify numerous endocrine cells in all but 1 case. Eleven sera against all the most common hormones stored in the endocrine cells of the gut were used to identify the main products of the cells. The following immunoreactivities were identified: 5-hydroxytryptamine (5-HT) (in 75% of the studied cases), somatostatin (87%), motilin (31%), pancreatic polypeptide (PP) (20%), glucose-dependent insulinotropic polypeptide (20%), gastrin (15%), glucagon (15%), peptide tyrosine tyrosine (13%), secretin (7%) and neurotensin (2%). No cholecystokinin-immunoreactive cells were identified. Our results indicated that, in Barrett's epithelium, both gastric and intestinal endocrine cells differentiate, in accordance with the variability of differentiation in the non-endocrine cells present in the different types of columnar epithelium. These findings provide support for the conclusion that Barrett's epithelium arises from a pluripotential stem cell capable of both gastric and intestinal differentiation.     

Light and electron microscopic identification of several types of endocrine cells in the gastrointestinal mucosa of the cat

Summary The following histological methods, previously proved to be useful in selective light microscopic detection of endocrine cells, were applied to the cat gastrointestinal mucosa: for the identification of biogenic amines, diazonium, ammoniacal silver and xanthydrol methods; for granules identification, methyl green-red acid dyes, toluidine blue, HCl-basic dye, lead-haematoxylin, phosphotungstic haematein and argyrophil methods. Results were compared with those of an extensive electron microscopic investigation.Five types of endocrine cells were identified in the gastric mucosa. Three types were found in the pyloric mucosa: the previously described 5-hydroxytryptamine-producing enterochromaffin cell, the gastrin producing G cell and a cell with an unknown function, labelled in this paper the X cell. Four types were found in the fundic mucosa: enterochromaffin cells (rarely observed), enterochromaffin-like cells secreting a 5-hydroxyindole but showing some ultrastructural and staining differences from true enterochromaffin cells (numerously present), A-like cells (few), resembling A cells of the pancreatic islets, and X cells, resembling those in the pyloric mucosa.In the intestinal mucosa, at least three endocrine cell types were distinguished in its duodenal part: enterochromaffin cells and two types of polypeptide-producing cells — some with smaller granules (S cells) and others with larger granules (L cells). Only two types were found in the mucosa of terminal ileum: enterochromaffin cells and numerously-occurring cells with large granules resembling in part duodenal L cells. The possibility of a relationship between S and L cells and the production respectively of the intestinal hormones secretin and cholecystokinin-pancreozymin was discussed.This investigation was supported by a grant N. 115/1139/0/4715 of the Italian Consiglio Nazionale delle Ricerche.     

Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa

Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.     

The occurrence of argyrophilic and argentaffin cells in the gut of Ciona intestinalis L.

Summary Argyrophilic and argentaffin cells occur in the stomach and intestinal epithelium of the sea-squirt, Ciona intestinalis L.. These cells are characterized by their basal swelling which contains the nucleus surrounded by small secretory granules and by a filamentous cell-apex which reaches the gut lumen. The cells are scattered unevenly within the epithelium. Their number decreases rapidly towards the lower part of the intestine. The localization, size of granules and their shape are features which differentiate these cells from other secretory cells in the gut epithelium such as mucous cells. These cells are thought to possess an endocrine function.The excellent technical assistance of Mrs. R. Sprang is gratefully acknowledged     

The reaction of the endocrine cells of the gastrointestinal tract in response to exposure to 3,6-dichloropicolinic acid

Silver-impregnated argentaffin cells both Ec, D1, G, P, S and K enteroendocrine cell types of rat gastrointestinal mucosa were investigated under light and electron microscopy after single oral administration of 3,6-dichloropicolinic acid. As a result, in pyloric-duodenal region Ec cells after a period of 1 hour had intensively secreted hormones. Ultrastructurally their cytoplasm and secretory granules were covered by expressed vacuolization. These data hypothetically elucidate the role of the endocrine regulations in developing barrier function of the gastrointestinal epithelium.     

Topology of chromogranins in secretory granules of endocrine cells

Summary Chromogranins A and B are glycoproteins originally detected in the adrenal medulla. These proteins are also present in a variety of neuroendocrine cells. The subcellular distribution of the chromogranins, and particularly their intra-granular topology are of special interest with respect to their putative functions.Endocrine cells of the guinea pig adrenal medulla, pancreas and gastric mucosa were investigated immunoelectron microscopically for the subcellular distribution of both chromogranins. Out of 13 established endocrine cell types in all locations, only two endocrine cell types showed immunoreactivity for both chromogranin A and B, and eight endocrine cell types showed immunoreactivities only for chromogranin A. These immunoreactivities varied inter-cellularly. Three endocrine cell types were unreactive for the chromogranins. Moreover, some hormonally non-identified endocrine cells in the pancreas and the gastric mucosa also contained chromogranin A immunoreactivities.Subcellularly, chromogranin A or B were confined to secretory granules. In most endocrine cells, the secretory granules showed chromogranin immunoreactivities of varying densities. Furthermore, the intra-granular topology of chromogranin A or B in the secretory granules varied considerably: in some endocrine cell types, i.e. chromaffin-, gastrin- and enterochromaffin-like-cells, chromogranin A immunoreactivity was localized in the perigranular and/or dense core region of the secretory granules; in others, i.e. insulin-, pancreatic polypeptide-and bovine adrenal medulla dodecapeptide-cells, it was present preferentially in the electron-opaque centre of the secretory granules; chromogranin B immunoreactivity was localized preferentially in the perigranular region of the secretory granules of chromaffin cells and gastrin-cells. The inter-cellular and inter-granular variations of chromogranin A and B immunoreactivities point to differences in biosynthesis or processing of the chromogranins among endocrine cells and their secretory granules.     

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.