Peptide Hormone-producing Cells Research Articles

Differential Expression of Secretogranins II and III in Canine Adrenal Chromaffin Cells and Pheochromocytomas.

Secretogranin II (SgII) and III (SgIII) function within peptide hormone-producing cells and are involved in secretory granule formation. However, their function in active amine-producing cells is not fully understood. In this study, we analyzed the expression profiles of SgII and SgIII in canine adrenal medulla and pheochromocytomas by immunohistochemical staining. In normal adrenal tissues, the intensity of coexpression of these two secretogranins (Sgs) differed from each chromaffin cell, although a complete match was not observed. The coexpression of vesicular monoamine transporter 2 (VMAT2) with SgIII was similar to that with chromogranin A, but there was a subpopulation of VMAT2-expressing cells that were negative or hardly detectable for SgII. These results are the first to indicate that there are distinct expression patterns for SgII and SgIII in adrenal chromaffin cells. Furthermore, the expression of these two Sgs varied in intensity among pheochromocytomas and did not necessarily correlate with clinical plasma catecholamine levels in patients. However, compared with SgIII, the expression of SgII was shown to be strong at the single-cell level in some tumor tissues. These findings provide a fundamental understanding of the expression differences between SgII and SgIII in normal adrenal chromaffin cells and pheochromocytomas.

Fundectomy with Greater Curvature Plication; New Modification for Patients with Morbid Obesity

Background: Obesity is a global epidemic. Laparoscopic greater curvature plication [LGCP] is a restrictive surgical procedure described for the first time on 1981 by Wilkinson. Fundectomy is a selective resection of the acid-producing segment of the stomach, with removal of peptide hormone-producing cells [the oxyntic mucosa] as a consequence of the fundectomy. Aim of the work: Our aim is to assess the feasibility and advantages of the novel modification for morbidly obese patients which include fundectomy with greater curvature plication. Patients and Methods: Ten patients were included in this study, which carried out at Al-Azhar University Hospital [New Damietta]. Results: Body mass index [BMI] ranged from 30 to 48 kg/m2 [the mean was 38.8 kg/m2]. Operative time ranged from 60 to 120 minutes [Mean time: 93.5 minutes]. The mean hospital stay time was 1.35 days. The mean estimated weight loss percentage [EWL%] was 29.1% at three months, 44.6% at six months, 60.4% at one year, and 72.4% at two years. EWL% was less than 50% for one patient which needs reoperation with Laparoscopic Sleeve Gastrectomy. Two patients [20%] developed heartburn due to gastroesophageal reflux disease [GERD]. Nine patients [90%] presented nausea, and vomiting was present in four patients [40%]. Conclusion: Fundectomy and Greater curvature plication is a feasible, safe, effective as a bariatric operation with avoidance of complications of other bariatric operations. As a new modification for bariatric surgery, this operation needs more investigations and longer periods for follow up.

Rat stomach ECL-cell histidine decarboxylase activity is suppressed by ergocalciferol but unaffected by parathyroid hormone and calcitonin

The ECL cells are peptide hormone-producing cells, rich in histamine and chromogranin A (CGA)-derived peptides, that operate under the control of gastrin. Gastrin and the ECL cells form a functional unit, the gastrin–ECL-cell axis. The aims of the present study were to examine (1) if calcitonin (CT), parathyroid hormone (PTH) and vitamin D affect the gastrin–ECL-cell axis (by measuring the activity of the histamine-forming enzyme, histidine decarboxylase (HDC), and the expression of HDC mRNA and CGA mRNA in the ECL cells), and (2) if activation of the gastrin–ECL-cell axis affects the parathyroid glands (by measuring plasma PTH and mRNA expression). We also examined the possibility that the oxyntic mucosa harbours vitamin D receptors. Fasted rats received intravenous infusion of PTH and CT with or without gastrin. PTH raised the blood Ca 2+ concentration, whereas CT infusion lowered it. Plasma PTH rose in response to CT, while serum gastrin remained unaffected. ECL-cell HDC was activated by gastrin but not by CT and PTH. Five daily subcutaneous injections of large amounts of ergocalciferol raised the blood Ca 2+ concentration, while reducing the oxyntic mucosal HDC activity and the expression of HDC and CGA mRNA. The serum gastrin concentration was not affected. The findings are in line with the idea that the gastrin–ECL-cell axis can be suppressed by vitamin D or by vitamin D-dependent mechanisms. Western blot analysis revealed the presence of vitamin D receptor immunoreactivity and reverse transcription PCR detected vitamin D receptor gene expression in the rat oxyntic mucosa. Hypergastrinemia was induced by daily peroral treatment with the H +/K +-ATPase inhibitor, omeprazole, for 2 weeks or by continuous subcutaneous infusion of gastrin for 7 days. Elevated serum gastrin concentration was associated with increased HDC activity and increased HDC and CGA mRNA expression in the oxyntic mucosa. There was no elevation of plasma PTH or PTH mRNA expression in the parathyroid gland.

Osteopenia after gastrectomy, fundectomy or antrectomy: an experimental study in the rat

Background: Gastrectomy induces osteopenia. In this study, we tested if resection of defined parts of the stomach could reproduce the gastrectomy-evoked osteopenia. Methods: Rats were subjected to gastrectomy (surgical removal of the glandular part of the stomach), fundectomy (extirpation of the acid-producing part, fundus) or antrectomy (extirpation of the gastrin-producing part, antrum). Calvariae, tibiae and femurs were examined at various times after the operations. The calvariae were subjected to transillumination. Calvariae and tibiae were sectioned and analysed by histomorphometry, tibia sections by the aid of a Merz grid and calvaria sections using computer-assisted image analysis. The intact femurs were subjected to computerized microtomography. Results: Gastrectomy (hypogastrinemia) and fundectomy (hypergastrinemia) resulted in osteopenia, while antrectomy (hypogastrinemia) had less effect on bone. Gastrectomy/fundectomy were associated with loss of trabecules in the tibia and with reduced bone volume in both tibia and calvaria. In contrast, there was only little reduction of cortical bone in the femur. Conclusion: Gastrectomy-evoked osteopenia can be reproduced by selective resection of the acid-producing part of the rat stomach (i.e. fundectomy). Antrectomy was less effective. In the long bones, the osteopenia was manifested primarily in trabecular bone and less in cortical bone. The calvaria displayed marked osteopenia. Although the findings indicate that the stomach, notably the acid-producing (oxyntic) mucosa, is important for bone metabolism, the precise mechanisms behind the gastrectomy/fundectomy-evoked osteopenia remain unidentified. Clearly, lack of gastrin is not responsible. The oxyntic mucosa is rich in peptide hormone-producing cells (the so-called ECL cells), with unidentified physiological significance. The ECL cells, which operate under the control of gastrin, have been put forward as a possible source of an osteotropic hormone.

Reversibility of omeprazole-evoked changes in the ultrastructure of ECL cells in the rat stomach.

The ECL cells are histamine- and peptide hormone-producing endocrine cells in the rat oxyntic mucosa. They are rich in secretory vesicles and also contain microvesicles and electron-dense granules. They operate under the control of circulating gastrin. In the present study, we examined the ECL-cell ultrastructure after long term treatment with omeprazole, which is known to induce hypergastrinemia, and after withdrawal of the drug. Rats received omeprazole (400 micromol/kg per day, orally) for 16 days and were killed 1, 5, 20, or 40 days after the last dose of the drug. Oxyntic mucosal specimens were processed for electron microscopy. Electron micrographs of ECL-cell profiles were analyzed planimetrically. The ECL-cell profile area increased promptly in response to omeprazole, the secretory vesicles and granules were reduced in number and volume density, the microvesicles were unchanged in number but reduced in volume density, and vacuoles appeared. Within a week after stopping the omeprazole treatment, the numbers and volume densities of secretory vesicles and microvesicles returned to pre-stimulation values. Also, the vacuoles disappeared promptly. The ECL-cell profile area decreased below the pre-stimulation level within five days after stopping treatment, while, in contrast, the granules increased in number and volume density. Somewhat surprisingly, the cell size and the granule compartment did not return to normal until 40 days after stopping treatment.

Perturbations in blood Ca(2)+ do not affect the activity of rat stomach enterochromaffin-like cells.

Gastrin stimulates uptake of Ca(2)+ into bone and causes transient hypocalcemia, possibly by releasing a peptide hormone from enterochromaffin-like (ECL) cells, which are histamine- and peptidehormone-producing cells in the acid-producing part of the stomach. However, if ECL cells secrete a calciotropic hormone, it is to be expected that their activity is affected by the serum Ca(2)+ concentration. Food-deprived male rats were infused with human (Leu)15-gastrin-17 and/or ethylenediamine-tetraacetic acid and CaCl(2). The blood Ca(2)+ level was monitored throughout the experiments (3 h), and the serum concentrations of gastrin, parathyroid hormone, and calcitonin were measured at death. The activity of the ECL cells was assessed by measuring the histidine decarboxylase (HDC) activity. Gastrin produced the expected increase in HDC activity, but neither hyper- nor hypo-calcemia affected the RDC activity of either hypo- or hyper-gastrinemic rats. Perturbations in blood Ca(2)+ do not seem to affect ECL cells, which is at odds with the view that ECL cells harbor a calciotropic hormone.

Molecular probing of the secretory pathway in peptide hormone-producing cells

The biosynthetic machinery in the melanotrope cells of the Xenopus intermediate pituitary is primarily dedicated to the generation of proopiomelanocortin (POMC)-derived, melanophore-stimulating peptides. Transfer of the animal to a black background stimulates the production of these peptides and causes a dramatic increase in POMC mRNA levels. To identify genes involved in the biosynthesis and regulated release of peptide hormones, we differentially screened an intermediate pituitary cDNA library of toads adapted to a black background with cDNA probes derived from intermediate pituitary mRNA of black- and white-adapted animals. Here we report the identification of twelve distinct genes whose expression levels in the melanotropes are regulated in coordination with that of POMC. Four of these genes are novel while the others code for translocon-associated proteins, a lumenal cysteine protease of the endoplasmic reticulum, prohormone-processing enzymes, members of the granin family and a transmembrane protein presumably involved in the assembly and/or specific functioning of vacuolar H(+)-ATPase from secretory granules. Our results indicate that a wide variety of both soluble and membrane-associated components of the secretory pathway is recruited in physiologically activated, peptide hormone-producing cells.

Chromogranin A and B in neuronal elements in Hirschsprung's disease: An immunocytochemical and radioimmunoassay study

Chromogranin A and B (CAB) occur in several peptide hormone-producing cells and in neurons of the brain. The aim of the present study was to investigate the possible neuronal localization of these chromogranins in the ganglionic and aganglionic bowel in Hirschsprung's disease by immunocytochemistry and radioimmunoassay, using antibodies recognizing either chromogranin A or both chromogranin A and B. Further, the coexistence of chromogranins and other neuronal constituents was studied. CAB were found in nerve fibers and occasionally in nerve cell bodies of submucous and myenteric ganglia in the ganglionic bowel, indicating that at least a population of chromogranin-immunoreactive nerve fibers is intrinsic in origin. CAB-immunoreactive fibers were numerous in the muscle layers of the aganglionic segment. These fibers contained tyrosine hydroxylase (TH), which indicates that they are adrenergic, in both ganglionic and aganglionic bowel. In the muscle layers of aganglionic (but not ganglionic) bowel, chromogranin A coexisted with galanin, neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). The concentration of CAB in smooth muscle specimens was higher in the aganglionic bowel than in the ganglionic bowel. Thus, chromogranins are present in the human enteric gut hyperinnervating the aganglionic bowel of Hirschsprung's disease.

Cell and Tissue Distribution of Lysosomal Cysteine Proteinases, Cathepsins B, H, and L, and their Biological Roles.

Cathepsins B, H, and L, representative lysosomal cysteine proteinases, have been shown to be involved in the degradation of proteins, generation of bioactive proteins, antigen processing, etc. Recent biochemical as well as Immunohisto/cytochemical studies have demonstrated that these enzymes are transferred from the trans Golgi network to lysosomes of cells, and in some cases, to secretory granules of certain endocrine cells, or they are secreted from cells. Localization of these enzymes in lysosomes differs depending on cell types even in the same tissues, suggesting that expression of these enzymes is regulated corresponding to cell specialization. Cathepsins B and H are localized in secretory granules of some peptide hormone-producing cells; particularly, cathepsin B is co-localized with renin in various endocrine cells producing active renin, indicating that cathepsin B is a major candidate of the renin converting enzyme. Moreover, these cysteine proteinases are secreted as their pro- or active forms from various tissue cells. In the resorption lacuna facing osteoclasts, secreted cathepsin L has been suggested to play a major role in the degradation of organic bone constituents, particularly collagen. Thus cathepsins B, H, and L act as biomodulators in various cells and tissues. In the present review, we introduce the precise localization of cathepsins B, H, and L and discuss their possible roles in cells and tissues.

Antiserum directed against chromogranin A and B (CAB) is a useful marker for peptide hormone-producing endocrine cells and tumors.

Certain proteins, such as the chromogranins, have a ubiquitous occurrence in nearly ail peptide hormone-producing cells. To date, little is known about their functional role as structural proteins, precursors of bioactive peptides, or enzymes. Such proteins may serve as markers for endocrine cells and tumors. In the present study, we have used an antiserum that recognizes both chromogranin A and B (CAB) to demonstrate peptide hormone-producing endocrine cells and tumors in humans. The antiserum demonstrated endocrine cells all along the gastrointestinal tract, most of the islet cells, the adrenomedullary cells, the thyroid C cells, scattered endocrine cells in the respiratory tract, and numerous cells in the adenohypophysis. The CAB-positive cells outnumbered those storing chromogranin A as studied in the intestines and the anterior pituitary. An array of different peptide hormone-producing tumor cells were also CAB-positive, including several types of islet cell tumors, gastric, intestinal, and bronchial carcinoids, medullary thyroid carcinomas, and pheochromocytomas. Thus, the CAB antiserum may help identify peptide hormone-producing cells and tumors.

Chemical coding of endocrine cells of the airways: presence of helodermin-like peptides

The epithelium of the airways is rich in endocrine cells containing serotonin and/or a wide variety of regulatory peptides. These cells usually occur in clusters in the lungs but are also found scattered in the larynx and trachea. In the present study, endocrine cells in the airways of mouse, rat, hamster, guinea pig, pig, sheep and squirrel monkey were examined for the presence of serotonin, helodermin-like peptides and other regulatory peptides using immunocytochemistry and radioimmunoassay. In addition, we looked for the protein gene product 9.5 (PGP), which occurs in many peptide hormone-producing endocrine cells in the body. Both clustered and scattered endocrine cells in the airways were found to display coexistence of serotonin and peptides, such as a helodermin-like peptide, calcitonin and calcitonin gene-related peptide (CGRP). The PGP-immunoreactive cells were numerous and included elements containing serotonin and/or regulatory peptides. An additional PGP-immunoreactive endocrine cell population lacked serotonin and regulatory peptides. Helodermin-immunoreactive material was demonstrated in endocrine cells of the airways in the mouse and hamster but not in any of the other species studied. Serotonin was an endocrine cell constituent in all the species studied. Calcitonin and CGRP could be demonstrated by immunocytochemistry in the mouse, rat, and hamster, but not in the guinea pig, sheep, pig and monkey.(ABSTRACT TRUNCATED AT 250 WORDS)

Session 4: Histamine-Producing Cells in the Stomach and Their Role in the Regulation of Acid Secretion

Histamine H2-receptor antagonists inhibit basal and all kinds of stimulated acid secretion with about the same effectiveness, and hence, local release of histamine is thought to be necessary for the stimulation of parietal cells. A local histamine pool is physiologically relevant only if it is within the diffusion distance of the parietal cells, if it is effectively mobilized by gastrin, and if it is endowed with the machinery for a rapid replenishment of the histamine that has been released. Histamine in the stomach occurs in endocrine cells (so-called enterochromaffin-like (ECL) cells), mast cells, and neurons. The ECL cells are peptide hormone-producing cells. In mammals they are located basally in the oxyntic gland area, in the chief-cell-rich region. Parietal cells predominate in t he mid-region. ECL cells respond readily to gastrin with histamine release and histamine resynthesis. Thus, the ECL cells fulfil important prerequisites of a physiologically relevant histamine pool. however, it is not apparent how the preferential localization of ECL cells at the base of the glands may be conducive to a direct effect of released histamine ont he parietal cells, unless histamine reaches the parietal cells via capillary transport from the glandular base. Mast cells are numerous int he stomach of, for example, man, pigs, dogs, and cats. They occur scattered throughout the stomach wall without any obvious relation to the parietal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Session 5: Trophic Effects of Gastrin

Gastrin is an important trophic hormone for the acid-producing part of the stomach. There is no solid evidence that gastrin is physiologically important as a trophic agent outside the stomach. The trophic effects in the stomach are manifested as an increased weight and thickness of the oxyntic mucosa and can be induced by both exogenous and endogenous gastrin--that is, in situations of long-lasting hypergastrinemia (treatment with effective antisecretagogues, partial fundectomy, or antrum exclusion). Removal of endogenous gastrin by antrectomy induces the opposite effects--that is, diminished weight and thickness of the oxyntic mucosa. Unlike all other peptide hormone-producing endocrine cells in the oxyntic mucosa, the so-called enterochromaffin-like (ECL) cells respond readily to gastrin. An acute gastrin challenge results in release of stored products from the ECL cells (such as histamine) and activation of cytoplasmic enzymes (such as histidine decarboxylase). Sustained elevation of circulating gastrin over days results in hypertrophy of the ECL cells and over weeks results in marked hyperplasia (at most a fivefold increase in the rat). The results in other species are similar but often somewhat less marked than in the rat.

Carcinoid granule extract contains antigenic determinants common to peptide hormone-producing cells and endocrine tumours

Some soluble proteins, such as the chromogranins, are found in nearly all peptide hormone-producing cells. Little is known about their functional role, although they may act as enzymes or represent structural proteins. In the present study we have isolated granules from an ileal carcinoid tumour and raised antibodies to protein constituents within them. The antiserum proved to be useful for the immunohistochemical demonstration of peptide hormone-producing endocrine tumours in general and for the demonstration of most peptide hormone-producing cells.

Properties of p19, a novel cAMP-dependent protein kinase substrate protein purified from bovine brain.

We report the purification from bovine brain and describe some of the properties of a 19-kDa protein, p19, which we have previously shown to undergo hormone-dependent, cAMP-mediated phosphorylation in several peptide hormone-producing tumor cells. The procedure for purifying p19 to apparent homogeneity utilized ammonium sulfate fractionation, sequential chromatography on DEAE-cellulose and phenyl-Sepharose, followed by fast protein liquid chromatography using a Mono Q and, finally, a C8 reverse-phase column. The yield was 0.3-0.5 mg of p19/kg of brain. The molecular weight (Mr = 19,000) and frictional ratio (f/f0 = 1.87) of p19, which were derived from its Stokes radius (33 A) and sedimentation constant (s20,w = 1.4), suggest that the native form of p19 is an asymmetrically shaped monomer. We provide evidence to suggest that p19 is isolated as a mixture of molecular forms consisting of an unphosphorylated form and of three phosphoforms indicative of multisite phosphorylation. These forms cosedimented on sucrose density gradients and coeluted on gel filtration, hydrophobic chromatography, and reverse-phase fast protein liquid chromatography. They were resolved from each other by anion-exchange chromatography. The unphosphorylated form (pI 6.2) was phosphorylated by catalytic subunit of cAMP-dependent protein kinase to a stoichiometry of 0.5 mol of P/mol of p19, thereby giving rise to the three phosphoforms (pI 5.8, pI 5.6, and pI 5.2, respectively). We conclude that p19 is a novel cAMP-dependent protein kinase substrate protein that is present in brain and in peptide hormone-producing tumor cells. Its function remains to be identified.

Identification in rat brain of a 19-kDa protein that comigrates on two-dimensional electrophoresis with p19, a hormonally regulated phosphoprotein of insulinoma cells.

We have previously shown that a set of 19-kDa cytosolic proteins, p19, undergoes hormone-dependent phosphorylation in several peptide hormone-producing tumor cells. Here we show, using comigration on two-dimensional electrophoresis with RIN-1122 rat insulinoma cell p19, that an identical set of 19-kDa proteins is present in rat brain but not in liver or skeletal muscle. We have partially purified p19 from rat brain and have compared the apparent isoelectric variants by tryptic peptide mapping. The data suggest that p19 is a novel phosphoprotein consisting of an unphosphorylated form and of three phosphoforms.

P19, A Hormonally Regulated Phosphoprotein of Peptide Hormone-Producing Cells: Secretagogue-Induced Phosphorylation in AtT-20 Mouse Pituitary Tumor Cells and in Rat and Hamster Insulinoma Cells*

P19, a group of 19,000 mol wt cytosolic proteins, with apparent isoelectric points of pI 5.9, pI 5.7, and pI 5.4, respectively, was identified in three peptide hormone-producing cell types: AtT20 mouse pituitary tumor cells, RIN-1122 rat insulinoma cells, and hamster insulinoma cells. Secretagogue-dependent phosphorylation of P19 was analyzed in 32P-labeled cells by two-dimensional electrophoresis and autoradiography. The results were quantitated by computer-assisted densitometry. Cellular levels of cAMP and hormone release were measured in parallel incubations. In addition to stimulating ACTH release, CRF raised the cellular level of cAMP and increased the 32P labeling of all three 19,000 mol wt proteins in AtT20 cells. Other agents known to act through cAMP, which included isoproterenol, forskolin, and 8-bromo-cAMP, mimicked the effect of CRF on both ACTH release and phosphorylation of P19. 12-O-Tetra-decanoylphorbol-13-acetate, a tumor-promoting phorbol ester, also stimulated both ACTH release and phosphorylation of P19. In contrast, although 40 mM K+ promoted ACTH release, it did not affect the phosphorylation of P19. Analogous findings were observed in insulinoma cells. Glucagon stimulated insulin release, increased cellular cAMP and promoted phosphorylation of P19 in RIN 1122 cells. 12-O-Tetradecanoylphorbol-13-acetate also enhanced insulin release and the phosphorylation of P19 in these cells. The results obtained with hamster insulinoma cells closely resembled the observations in RIN-1122 cells. In conclusion, P19, an apparently homologous set of cytosolic proteins, undergoes phosphorylation in three peptide hormone-producing cells in response to two groups of secretagogues, the effect of which is probably mediated, in one case, by cAMP-dependent protein kinase and, in the other, by protein kinase C. The data suggest the possibility that P19 participates in a secretory pathway activated by these two effector systems.

Differences in the Cell Surface Antigens of Prolactin Producing Cells of Human Decidual and Pituitary Tissues*

Anterior pituitary cells and other endocrine cells which synthesize and release protein hormones share the cell surface ganglioside antigens A2B5 and 3G5. In addition, these peptide hormone-producing cells contain chromogranin, a major protein component of secretory vesicles. Since human decidual cells synthesize and release a PRL that has chemical and biological properties indistinguishable from those of pituitary PRL, we examined by immunochemical techniques whether decidual cells also contain cell surface antigens A2B5, 3G5, and chromogranin. In these studies, human decidual tissue from three pregnancies and human and rat pituitary tissues were processed and stained with mouse monoclonal antibodies to A2B5, 3G5, and chromogranin by indirect immunofluorescence using fluorescein-conjugated sheep antimouse gamma-globulin. In all instances, the pituitary and pancreatic tissue stained strongly with the monoclonal antibodies to the cell surface antigens, but the decidual tissues from the three pregnancies did not. The pituitary and pancreatic cells also stained strongly with the monoclonal antibody (LK 2H10) to chromogranin, but the decidual tissues had no reactivity. In control experiments, the decidual tissues stained strongly with a monoclonal antibody to HLA antigens, and none of the tissues stained with nonimmune gamma-globulin. These results strongly suggest that the PRL-producing cells of human decidua and pituitary have different cell surface antigens. The observation that decidual cells do not contain chromogranin is consistent with previous biochemical studies suggesting that decidual PRL is not stored in secretory granules. The differences in the subcellular localization of PRL in decidual and pituitary tissues may explain, in part, the differences in the regulation of PRL release from these tissues.

Immunohistological localization of growth hormone-releasing hormone in human tumors.

Two forms of GH-releasing factor (GHRH), which play a role in the regulation of GH secretion, have been isolated from pancreatic endocrine tumors in two patients with acromegaly. We examined formalin-fixed, paraffin-embedded human tissues from autopsies and surgical specimens for the presence of human pancreatic GHRH-40 using the avidin-biotin-peroxidase complex technique to assess the prevalence of tumors containing GHRH, to define their primary sites and cellular derivations, and to correlate clinical and pathological features. Immunopositivity was demonstrated in 4 of 24 pancreatic endocrine tumors, 1 of 5 bronchial and 2 of 15 gut carcinoids, 1 of 2 thymic carcinoids, 2 of 20 medullary carcinomas of the thyroid, 1 of 12 pheochromocytomas, and 5 of 20 small cell carcinomas of the lung. Of the GHRH-containing tumors, only 2 of the pancreatic endocrine tumors and the bronchial carcinoid were associated with acromegaly. No GHRH was found in 35 tumors derived from cells that are not known to produce peptide hormones. Immunoreactivity was not detected in the nontumorous tissues from which GHRH-containing tumors were derived. It can be concluded that GHRH may be found in a variety of tumors arising from and composed of peptide hormone-producing endocrine cells. The significance of immunoreactive GHRH detected in tumors unassociated with clinical evidence of acromegaly remains to be established.

What's New in Endocrine Factors of Tumor Growth?

In this review some aspects of endocrinological factors in cancer are discussed. The first part addresses the determination of steroid hormone receptors in cancer of the breast. The importance of steroid hormone receptor determination for the clinical management of breast cancer patients is emphasized. Current methods for receptor measurement are critically evaluated and it is concluded that rigorous standardization of tissue handling procedures and of radiochemical methodology is mandatory to improve the reliability of the presently available methods. The development of new techniques for receptor determination has been met with high expectations. Monoclonal antireceptor antibodies in principle allow the development of a radioimmunoassay but are not widely available as yet. Histochemical methods for receptor localization have so far failed to meet accepted criteria of specificity. Therefore radiochemical determination at present remains the only reliable method. The second part addresses the production of peptide hormones by endocrine tumours of the gastroenteropancreatic (GEP) system and by non-neuroendocrine neoplasms. In the endocrine tumours of the GEP system a wide range of peptide hormones can be detected by immunocytochemistry, but most frequently the pattern of hormone production is comparable with that in the normal organ of origin. Clinical symptoms of excess hormone production occur much less frequently than hormone production is found by immunological methods and is usually caused by one hormone. It is proposed that these neoplasms are classified according to the hormone which causes the leading clinical symptoms and/or the hormone with the highest serum level. Peptide hormone producing cells in classical carcinoma are an intriguing phenomenon which has shed some new light on the embryological origin of neuroendocrine cells in the relevant organs and also on the histogenesis of neuroendocrine as well as non-neuroendocrine neoplasms.