Immunoreactive Endocrine Cells Research Articles

An histological and immunocytochemical study of the neuroendocrine cells in the intestine of Podarcis hispanica Steindachner, 1870 (Lacertidae)

Numerous endocrine cells can be observed in the gut of the lizard Podarcis hispanica after application of the Grimelius silver nitrate technique. The argyrophilic endocrine cells are usually tall and thin in the small intestine but short, basal, and round in the large intestine. Eleven types of immunoreactive endocrine cells have been identified by immunocytochemical methods. Numerous serotonin-, caerulein/gastrin/cholecystokinin octapeptide-and peptide tyrosine-tyrosine-immunoreactive cells; a moderate number of pancreatic polypeptide-, neurotensin-, somatostatin-, glucagon-like peptide-1-and glucagon-immunoreactive cells, and few cholecystokinin N-terminal-and bombesin-immunoreactive cells were found in the epithelium of the small intestine. Coexistence of glucagon with GLP-1 or PP/PYY has been observed in some cells. In the large intestine a small number of serotonin-, peptide tyrosine-tyrosine-, pancreatic polypeptide-, neurotensin-, somatostatin-and glucagon-like peptide-1-immunoreactive cells were detected. Vasoactive intestinal peptide immunoreactivity was found in nerve fibers of the muscular layer. Substance P-immunoreactive nerve fibers were detected in lamina propria, submucosa and muscular layer. Chromogranin A-immunoreactive cells were observed throughout the intestine, although in lower numbers than argyrophilic cells.

The complete primary structure of pancreatic polypeptide from the European common frog, Rana temporaria

Using an antiserum directed against the highly-conserved C-terminal hexapeptide amide of mammalian pancreatic polypeptide (PP), numerous immunoreactive endocrine cells were identified within the pancreas of the European common frog, R. temporaria. An acidified ethanolic extract of pancreatic tissue (0.859 g, n = 35) contained 26.2 nmol equivalents/g of tissue. Gel permeation chromatography of the extract resolved a single peak of immunoreactivity co-eluting with synthetic bovine PP standard. Reverse phase HPLC of this material resolved a single peak of immunoreactivity which was purified to homogeneity following chromatography on a semipreparative C-18 column and an analytical C-8 column. Plasma desorption mass spectrometry (PDMS) of the purified peptide resolved a single component with a molecular mass of 4240.9 Da. Direct gas phase sequencing established the sequence of the first 26 residues. Following incubation of the peptide with endopeptidase Asp-N and direct application of the digest to the sequencer, the entire primary structure of the peptide was established as: APSEPHHPGDQATQDQLAQYYSDLYQYITFVTRPRF. The derived molecular mass of this peptide, incorporating a C-terminal amide, was 4240.6 Da which is entirely consistent with that obtained by PDMS.

Distribution of neuropeptide Y-like immunoreactivity in the normoganglionic and aganglionic segments of human colon

The localisation and distribution of neuropeptide Y (NPY)-like immunoreactivity were studied by use of immunohistochemical methods in gut tissues from 19 patients with Hirschsprung's disease, including 4 cases of long segment aganglionosis. In the normoganglionic segment, immunoreactive cell bodies and nonvaricose processes were seen within both myenteric and submucous plexuses. A scarce supply of varicose fibres was found in the lamina propria mucosae, muscularis mucosae and longitudinal muscle layer. NPY fibres were more frequently encountered in the circular muscle layer, although with a weakly immunostaining intensity. In addition, blood vessels in the submucosal connective tissue were surrounded by a typical plexus of varicose, NPY-positive fibres. Immunoreactive endocrine cells could be detected in the colonic epithelium. In the aganglionic segment, numerous nerve fasciculi comprising a small to moderate number of NPY fibres with varicosities were observed throughout the entire layer of the colonic wall. A few varicose, NPY-positive fibres were also contained in the relatively large, hypertrophic nerve fasciculi located in the intermuscular zone and submucosal connective tissue. NPY-immunoreactive fasciculi were more densely distributed in the distal aganglionic segment than in the proximal aganglionic one. On the other hand, the distribution of NPY-positive fibres in long segment aganglionosis was quite different from that in short segment type; in cases of long segment type, no immunoreactive nerve fibres were detected within the circular muscle layer of the proximal aganglionic segment near the oligoganglionic segment and only a few fibres were observed within the hypertrophic nerve bundle of the intermuscular zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine suppresses both photoreceptor and neuron-like properties expressed by cultured rat pineal glands

Our previous study showed that pineal glands of the newborn rat express properties of both photoreceptors and endocrine cells, when transferred to cell culture conditions, whereas opsin was not detected in cells of the intact pineal glands of the postnatally developing or mature rats (Araki et al., 1988). In the present study we asked a question why photoreceptor-like cells do not differentiate in vivo, although the pineal cells have the potency as revealed in cell culture conditions. Our hypothesis was that norepinephrine (NE) may suppress the differentiation of cells with photoreceptor properties. This was proved by adding NE into the culture medium, and only few opsin-like immunoreactive cells, if any, were differentiated in the presence of 10 −6 M NE. NE also suppresses the extension of neurite-like processes by serotonin-like immunoreactive (endocrine) cells, another property expressed in cultures. Other aminergic neurotransmitters, such as dopamine and serotonin, did not have such effects. These results imply that the massive innervations of the pineal gland by the sympathetic ganglion may suppress both photoreceptor and neuron-like properties of the mammalian pineal gland in vivo.

Serotonergic neurons in the intestine of two teleosts, Carassius auratus and Oreochromis mossambicus, and the effect of serotonin on transepithelial ion-selectivity and muscle tension

The application of an antiserum directed against rat serotonin demonstrated serotonin-immunoreactive cell bodies and varicose nerve fibres in the myenteric plexus of both goldfish and tilapia. In the circular muscle layer immunoreactive varicose nerve fibres and a few cell bodies could be detected. A fine network of varicose fibres was observed underlying the epithelial cells. Serotonin immunoreactivity was not observed along incoming mesenterial blood vessels, suggesting that the serotonergic neurons may be intrinsic to the intestine. Immunoreactive endocrine cells were shown in the intestinal epithelium of tilapia but not in goldfish. Serotonin caused a weak contraction of the intestinal wall of the goldfish which could be blocked by tetrodotoxin and by atropine, suggesting that serotonin has an indirect action on muscular contraction. In contrast, serotonin induced a relaxation of the intestinal wall of tilapia which could not be blocked by propranolol or by tetrodotoxin. This indicates that in this species serotonin may act directly on the muscle fibres. The ion-selectivity of the intestinal epithelium of both species was modulated by serotonin. Tetrodotoxin did not inhibit this effect, suggesting that serotonin acts directly on the epithelial cells. The presence of serotonergic fibres in the muscle layer and directly underneath the epithelium, along with the effect of serotonin on muscular tension and on the ion-selectivity of the epithelium, suggests that serotonin may play a role in the regulation of motility and the epithelial function of goldfish and tilapia intestine.

Ontogeny and differentiation of regulatory peptide-and serotonin-immunoreactivity in the gastrointestinal tract of an elasmobranch

A number of regulatory peptides and serotonin were studied by immunocytochemistry with respect to their appearance and distribution in the developing gastrointestinal tract of the selachian Scyliorhinus stellaris. In the earliest stage studied (fourth month developmental stage) glucagon-, somatostatin-, serotonin-, vasoactive intestinal peptide (VIP)-, cholecystokinin (CCK)-, and gastrin-immunoreactive cells were detected in the already differentiated intestinal epithelium, whereas only glucagon-, somatostatin-, and serotonin-immunoreactive cells were seen in the not yet differentiated stomach epithelium. Glucagon-immunoreactive cells were present in the gastric portion only; in the pyloric portion, they appeared in the next stage, together with CCK-, peptide histidine isoleucine (PHI)-, and bombesin-immunoreactive cells, and disappeared before birth. PHI-immunoreactive cells were restricted to the pyloric portion, whereas VIP- and gastrin-immunoreactive cells were detected in the spiral gut only. At the beginning, immunoreactive cells were few, but they grew in number until birth, when some of them presented a more elevated frequency than that seen in adults. Immunoreactive endocrine cells were of open type and showed a distribution similar to that seen in adults. PHI-immunoreactive nerve fibers appeared early, first in the lamina propria, then in the muscular layer; the opposite was seen for VIP-immunoreactive fibers that were shown successively, first in the muscular layer, then in the lamina propria. Intestinal bombesin and β-endorphin were shown after birth only. The early appearance of the peptides tested is consistent with the hypothesis that they play a role on cell growth and differentiation.

Immunohistochemical colocalization of delta sleep-inducing peptide and luteinizing hormone-releasing hormone in rabbit brain neurons

The anatomical distributions of luteinizing hormone-releasing hormone and delta sleep-inducing peptide immunoreactivity in the rabbit brain were studied by indirect immunofluorescence technique. The comparison of adjacent serial sections, one being immunolabelled with an antiserum to luteinizing hormone-releasing hormone, the other with an antiserum to delta sleep-inducing peptide, showed that the respective distribution patterns of immunoreactivity exhibited a remarkable overlap through the basal forebrain and hypothalamic regions. A sequential double-immunolabelling (elutionrestaining method) clearly indicated that all the luteinizing hormone-releasing hormone-immunoreactive cell bodies displayed delta sleep-inducing peptide immunoreactivity. These cell bodies were sparse and mainly located throughout the septal-preoptico-suprachiasmatic region and the ventrolateral hypothalamus. The colocalization of luteinizing hormone-releasing hormone and delta sleep-inducing peptide immunoreactivity was also observed in many fibres supplying all these brain regions and terminal areas such as the organum vasculosum of the lamina terminalis, the subfornical organ, the median eminence and the pituitary stalk. These neuroanatomical findings are suggestive of interaction between delta sleep-inducing peptide and luteinizing hormone-releasing hormone in various brain areas including some circumventricular organs.

Distribution and ontogeny of VIP-like immunoreactivity in the gastro-entero-pancreatic system of a cartilaginous fish Scyliorhinus stellaris.

The presence, distribution and development of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the gastro-entero-pancreatic system of a cartilaginous fish Scyliorhinus stellaris (L.) was investigated by immunohistochemical methods utilizing mammalian VIP antisera. In the gut VIP-like immunoreactivity was observed in both nerves and endocrine cells. Endocrine cells with VIP-like material were only detected in the intestinal epithelium while nerve fibres containing VIP-like material were noted along the whole gastro-entero-pancreatic system, being more numerous in the pyloric sphincter and in the intestinal portion. Immunoreactive nerve cell bodies were encountered in the stomach and intestinal portions localized in the submucosa and in the myenteric plexus. Intestinal immunoreactive endocrine cells were already present in the first developmental stage considered (embryos aged 4 months). They grow in number and before birth reach a frequency higher than in adults. Nerves and cell bodies showing VIP-like immunoreactivity, appear later, before birth, as a few elements in the smooth muscular layer, but only after birth their distribution and frequency are similar to those found in adults. The faint immunofluorescence shown by the immunoreactive endocrine cells and their developmental pattern, which is always different from that observed in nervous elements, suggest the presence of at least two VIP-like substances in the gastro-entero-pancreatic system of S. stellaris.

Argyrophilic and hormone immunoreactive cells in normal and hyperplastic pancreatic ducts and exocrine pancreatic carcinoma

Scattered argyrophil cells were present in normal, large, medium-sized and small pancreatic ducts (ductules). There was marked increase in argyrophil cells in ducts with hyperplastic epithelium. Argyrophil cells were also found in 67.7% of all exocrine pancreatic carcinomas. In a well differentiated group including cystadenocarcinoma, mucinous carcinoma and well differentiated ductal adenocarcinoma argyrophil cells were found in all cases examined. Using four antisera (against insulin, glucagon, somatostatin and gastrin), insulin, glucagon and somatostatin cells were identified in 2.65%, 0.001% and 1.2% of normal ducts, and 7.5%, 2.4% and 4.6% of ducts with hyperplastic epithelium respectively and were also greatly increased in numbers in the latter group. Immunoreactive cells were present in 66.7% of exocrine carcinomas. Cells reactive for insulin were found in 7/15 cases; glucagon in 6/15 cases; somatostatin in 5/15 cases and gastrin in 2/15 cases. Eight cases contained two or more than two types of immunoreactive cells. The presence of argyrophil and hormone immunoreactive cells in pancreatic ducts and carcinomas is indicative of the close developmental relationship between endocrine and exocrine parts of the pancreas. The inter-relationship of response in the different cell types following stimulus suggests that injury to a common precursor may be involved.

An Immunohistochemical Study of the Gastrointestinal Endocrine-Cells of the New Holland Honeyeater, Phylidonyris-Novaehollandiae

The gastrointestinal tract of the New Holland honeyeater, Phylidonyris novaehollandiae, was studied macroscopically, histologically and immunohistochemically. Although the honeyeater did not differ from other birds at the macroscopic and histological level, some interesting differences were revealed immunohistochemically. Eight types of immunoreactive endocrine cells were detected in the gastro- intestinal mucosa. The proventriculus and gizzard were characterised by the presence of serotonin-, somatostatin-, and gastrin-releasing polypeptide-immunoreactive cells. The pyloric region contained numerous gastrin- and motilin-immunoreactive cells as well as moderate numbers of somatostatin- immunoreactive cells. Along the length of the intestine, serotonin-immunoreactive cells were the dominant endocrine cells but small numbers of somatostatin-, gastrin-, enteroglucagon-, pancreatic glucagon- and neurotensin-immunoreactive cells were also found. Each had a different distribution pattern. The functional significance of these results remains to be resolved.

Systemic angiotensin acts at the subfornical organ to control the activity of paraventricular nucleus neurons with identified projections to the median eminence.

The present studies were carried out to investigate the mechanisms through which systemic angiotensin II (AII) acts within the central nervous system to influence the release of anterior pituitary hormones in the Sprague-Dawley rat. In particular, these studies have examined the role of the subfornical organ (SFO) as an essential structure mediating these responses. Extracellular single-unit recordings were obtained from 199 paraventricular nucleus (PVN) neurons antidromically identified as projecting to the median eminence. Different groups of these neurons were tested for the effects of either electrical stimulation in the SFO (n = 87) or systemic AII administration in intact (n = 49) and SFO-lesioned (n = 25) animals. Of cells tested with SFO stimulation 45% were excited, 16% inhibited, and the remainder unaffected. Neurons which were excited were primarily located just medial to the magnocellular neurons in the region where the majority of corticotropin-releasing hormone immunoreactive cells are found. In contrast, inhibitory responses were observed in cells located in the dorsal medial PVN, a region containing thyrotropin-releasing hormone, somatostatin, and dopamine PVN-median eminence neurons. Following systemic AII 42% of cells tested showed increased activity specific to the effects of this peptide, and 20% showed alterations in activity associated with the cardiovascular changes induced by AII. In contrast, following SFO lesion only 8% of neurons tested showed specific excitatory responses to AII. In order to test the hypothesis that systemic AII may activate this excitatory SFO to PVN pathway, a further group of 35 neurons were tested with both SFO stimulation and AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization in the gastrointestinal tract of immunoreactive prosomatostatin

Antisera against 5 different regions of the entire prosomatostatin molecule were used for immunohistochemical mapping of prosomatostatin-containing structures in the pig gastrointestinal tract, and for radioimmunological and chromatographical analysis of the products of prosomatostatin in extracts of ileal mucosa. The latter showed that the antisera were capable of identifying components containing N-terminal as well as C-terminal parts of prosomatostatin. Endocrine cells were identified with all antisera in most parts of the gastrointestinal tract, and varicose nerve fibres were observed in all parts of the small intestine but not in the stomach and the colon. The colon contained very few immunoreactive structures. Immunoreactive nerve cell bodies were found in the submucous plexus of the small intestine. All immunoreactive endocrine cells in the stomach and the duodenum and all immunoreactive nerves were stained by all 5 antisera whereas the small intestinal endocrine cells did not stain for the most N-terminal region of prosomatostatin. The results suggest that all gastrointestinal somatostatin is derived from the same precursor molecule, which, however, in the small intestinal endocrine cells is processed differently from that of the other tissues.

Papillary cystic tumor of the pancreas. An analysis of cellular differentiation by electron microscopy and immunohistochemistry.

Three cases of clinically benign pancreatic papillary cystic tumors in young female patients were studied by immunohistochemistry and electron microscopy in order to define the cellular nature of this type of neoplasm. Two of the tumors showed focal cytokeratin- and desmoplakin-positivity as evidence of focal epithelial differentiation, while the tumor cells were in all cases positive for vimentin--the intermediate filament protein typical of (but not specific for) mesenchymal cells. Electron microscopy showed some cell-cell junctions, but there was no evidence of acinar or islet cell differentiation. The tumors were at least focally positive for neuron-specific enolase, and small clusters of polypeptide hormone immunoreactive cells were present in all cases (glucagon 3/3, somatostatin 2/3, insulin 2/3). However, the tumors were negative for synaptophysin and neurofilament proteins, unlike most islet cell tumors. Trypsin and chymotrypsin immunoreactivity was found in all tumors, but because many nonpancreatic carcinomas were also positive, we doubt whether these two enzyme proteins can act as specific markers for pancreatic acinar cell differentiation. Two of the tumors that were studied immunohistochemically for the presence of nuclear estrogen receptors, were negative. Therefore no proof of the suggested hormone dependence of this tumor could be obtained. We conclude that papillary cystic tumor is a neoplasm of primitive pancreatic epithelial cells, that may exhibit focal endocrine cell differentiation.

Gastrin/CCK-like immunoreactivity in endocrine cells and nerves in the gastrointestinal tract of the cod, Gadus morhua, and the effect of peptides of the gastrin/CCK family on cod gastrointestinal smooth muscle

Immunohistochemistry shows the presence of one or several gastrin/cholecystokinin (CCK)-like peptides in the gastrointestinal tract of the Atlantic cod, Gadus morhua. Immunoreactive (IR) endocrine cells are present mainly in the lower part of the cardiac and in the pyloric stomach, with a concentration to the inner curvature, and in the proximal part of the intestine, especially in the area of the pyloric caeca, after which the population density of IR cells decreases anally. IR nerve fibers are found in the myenteric plexus and muscle layers of the stomach only. Radioimmunoassays, performed with two C-terminal specific gastrin/CCK antisera, confirm the immunohistochemical findings. The highest levels of IR material are found in the mucosa of the pyloric caeca, the proximal intestine, and the pyloric part of the stomach. The smooth muscle layers contain IR material in decreasing gradient toward the rectum. The excitatory effect of gastrin/CCK-related peptides on gut smooth muscle is investigated in isolated strip preparations of the gut wall. Of the peptides tested, cerulein is the most potent, followed by CCK 8.and gastrin 17, while gastrin 5 is the least effective. Sulphated CCK 8 gives a higher amplitude of the response but in the same concentration range as nonsulphated CCK 8. It is concluded that one or several gastrin/CCK-like peptides are present in the gut of the cod and may be involved in the nervous and endocrine control of the cod gut motility.

Neoplastic endocrine cells in carcinomas of the small intestine:: Histochemical and immunohistochemical studies of 24 tumors

Endocrine cells in 24 primary carcinomas and in the nonneoplastic mucosa of the small intestine were investigated histochemically and immunohistochemically with antisera against serotonin and 10 kinds of peptide hormones. Argyrophil-positive endocrine cells were found in four of eight duodenal, all of eight jejunal, and six of eight ileal carcinomas. The density of the positive cells was higher in the ileal tumors than in the duodenal and jejunal ones. Immunoreactive endocrine cells were detected in three duodenal, six jejunal, and five ileal carcinomas. Immunoreactive serotonin cells were present most frequently and most densely without respect to the site of origin of the carcinomas. In general, the population of endocrine cells among the tumor cells was higher in the ileal carcinomas than in the duodenal and jejunal ones. The ileal carcinomas frequently and densely demonstrated somatostatin, peptide YY, neurotensin, glucagon, and glicentin cells in addition to serotonin cells. The kinds of endocrine cells and the relative frequency of each kind of endocrine cell in carcinomas of the small intestine were similar to those in the nonneoplastic mucosa from which the carcinomas originated. This is the first systematic immunohistochemical study on endocrine cells in carcinoma of the small intestine.

An immunohistochemical study on the distribution of endocrine cells in the gastrointestinal tract of the pig.

Regional distribution and relative frequency of endocrine cells were studied in fifteen portions of the porcine gastrointestinal tract by immunohistochemical methods. Twelve kinds of immunoreactive endocrine cells were identified in this study. In the stomach, 5-HT-, somatostatin-, gastrin-, methionine-enkephalin-Arg6-Gly7-Leu8 (M-ENK-8)-, glucagon- and bovine pancreatic polypeptide (BPP)-immunoreactive cells were detected. The first four cell types were predominant over the other types and were more numerous in the pyloric region than in the cardiac and fundic regions. In the small intestine, 5-HT-, somatostatin-, gastrin, M-ENK-8-, motilin-, secretin-, cholecystokinin (CCK)- and gastric inhibitory polypeptide (GIP)-immunoreactive cells were widely distributed and most numerous in the duodenum, while neurotensin- and glicentin-immunoreactive cells were predominant in the ileum. Glucagon- and BPP-immunoreactive cells were rarely seen in the small intestine. In the large intestine, 5-HT-, somatostatin- and glicentin-immunoreactive cells were widely distributed and most numerous in the rectum. Motilin-, glucagon- and BPP-immunoreactive cells were rarely seen in the large intestine. It is suggested that the distribution pattern of gut endocrine cells in pigs is the most similar to that in humans among the mammalian species so far reported.

Appearance of immunoreactive endocrine cells during the development of the rat pancreas, with special reference to polypeptide-secreting cells.

The chronological appearance of PP cells in fetal pancreatic islets was studied using specific anti-PP serum and the direct peroxidase method. The presence of A and B cells was also studied, using the same immunocytochemical technique, as a reference pattern related to data previously reported. Our data confirm that the A cell is the earliest endocrine cell type, appearing on the 12th day of gestation, followed by B cells (14th day) and later on by PP cells (19th day). Primitive islets were identified in the pancreas after the 15th day. However, the spatial cell disposition observed in the adult islet was only recognized at the 20th day of gestation. The data reported provide the necessary information to establish the complete chronology in the rat fetus. Consequently, the development of pancreatic islets in the rat fetus could be employed as a useful model to study the existence of factors that control the sequential appearance of endocrine cells and the possible changes occurring in the islets of animals with genetic diabetes during the fetal period.

Immunocytochemical identification and localization of peptide hormones in the gastro-entero-pancreatic (GEP) endocrine system of the mouse and a stomachless fish, Barbus conchonius.

A large number of antisera mainly raised against mammalian hormones are tested immunocytochemically on the GEP-endocrine system of mouse and fish (Barbus conchonius). The endocrine pancreas of mouse and fish appeared to contain the same four endocrine cell types; insulin-, glucagon-, PP- and somatostatin-immunoreactive cells. In mouse about 13 GEP endocrine cell types are distinguished: 1. insulin-, 2. somatostatin-, 3. glucagon-, 4. PP-, 5. (entero)glucagon-/PP-like, 6. CCK-like, 7. substance P-, 8. neurotensin-, 9. VIP-, 10. gastrin-, 11. secretin-, 12. beta-endorphin-, 13. serotonin-immunoreactive cells. Based on this and a previous study at least 13 GEP endocrine cell types seems to be present in stomachless fish: 1-9 as described for mouse, 10. (entero)glucagon-like, 11. met-enkephalin, 12. VIP-like, 13. unspecific immunoreactive endocrine cells. Coexistence of glucagon and PP-like peptides is found in the gut and pancreas of mice and in the gut of B. conchonius. In mouse pancreas and fish gut, endocrine cells showing only PP- or glucagon-like immunoreactivity are found too. In mouse stomach some endocrine cells showing only PP-immunoreactivity are demonstrated. In the same region coexistence of C-t-gastrin- and FMRF-amide-immunoreactivity is found in endocrine cells. The importance of these phenomena are discussed. Enteric nerves immunoreactive with antisera raised against substance P and GRP are found in mouse, against somatostatin and met-enkephalin in both mouse and fish and against VIP in fish.

An immunocytochemical study of regulatory peptides in the amphibian gastrointestinal tract

Samples from the gastrointestinal tract of two urodele and eight anuran species were investigated by immunocytochemical methods for the presence of structures immunoreactive with a range of antisera raised to the mammalian regulatory peptides. The regulatory peptides involved were gastrin, cholecystokinin, motilin, secretin, gastric inhibitory polypeptide, pancreatic glucagon, enteroglucagon, glicentin, neurotensin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, substance P, Met-enkephalin, bombesin, and β-endorphin. In the majority of the species investigated, immunoreactive epithelial endocrine cells were demonstrated with the antisera to somatostatin, gastrin, enteroglucagon, and neurotensin. Motilin-containing cells were observed in a single species, Ambystoma mexicanum. Of the peptides detected within the mammalian innervation, vasoactive intestinal polypeptide, substance P, Met-enkephalin, and β-endorphin immunoreactive nerve fibres were seen. The distribution of the immunoreactive nerves differed significantly with species. Bombesin immunoreactivity was not seen within the innervation, although a population of endocrine cells was detected within the corpus of several species. No immunoreactivity was observed with the antisera to secretin, gastric inhibitory polypeptide, or pancreatic polypeptide in the species investigated.

Pituitary Adenomas Associated With Hyperprolactinemia: A Clinical and Immunohistochemical Study of 97 Patients Operated on Transsphenoidally

Immunohistochemical studies were performed on the tumors of 97 of 100 patients who had undergone an operation for a presumed prolactin-secreting pituitary adenoma; no tissue was available for study in the other 3 patients. Appropriate immunohistochemical studies were done to identify the presence of growth hormone, prolactin, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone within the adenoma cells. The presence of a prolactin-producing pituitary adenoma was confirmed in 91 patients, 3 of whom had an adenoma that consisted of cells that contained prolactin and growth hormone. One other patient, not counted among the 91 with prolactinoma, had lactotrope and thyrotrope hyperplasia. Among the five patients whose adenoma did not contain prolactin cells, four had a null cell adenoma and one had a tumor consisting of follicle-stimulating hormone and luteinizing hormone immunoreactive cells. On the basis of preoperative serum prolactin values in these patients, we concluded that moderately increased values (30 to 200 ng/ml) of serum prolactin are not a reliable guide for determining whether a prolactin-producing pituitary adenoma is present, whereas levels exceeding 200 ng/ml are usually associated with a prolactin-secreting tumor.