Genome-wide association study of body fat distribution identifies adiposity loci and sex-specific genetic effects.

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested to be more pathogenic compared to fat stored in other compartments. In this study, we perform genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. 98 independent associations with body fat distribution are identified, 29 that have not previously been associated with anthropometric traits. A high degree of sex-heterogeneity is observed and the effects of 37 associated variants are stronger in females compared to males. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling.

Triacylglycerol estolides, a new class of mammalian lipids, in the paracloacal gland of the brushtail possum (Trichosurus vulpecula).

The paracloacal glands are the most prevalent scent glands in marsupials, and previous investigation of their secretions in the brushtail possum (Trichosurus vulpecula) has identified many odorous compounds together with large amounts of neutral lipids. We have examined the lipids by LC-MS, generating ammonium adducts of acylglycerols by electrospray ionisation. Chromatograms showed a complex mixture of coeluting acylglycerols, with m/z from about 404 to 1048. Plots of single [M + NH4](+) ions showed three groups of lipids clearly separated by retention time. MS-MS enabled triacylglycerols and diacylglycerol ethers to be identified from neutral losses and formation of diacylglycerols and other product ions. The earliest-eluting lipids were found to be triacylglycerol estolides, in which a fourth fatty acid forms an ester link with a hydroxy fatty acid attached to the glycerol chain. This is the first report of triacylglycerol estolides in animals. They form a complex mixture with the triacylglycerols and diacylglycerol ethers of lipids with short- and long-chain fatty acids with varying degrees of unsaturation. This complexity suggests a functional role, possibly in social communication.

Function and composition of male accessory gland secretions in Anopheles gambiae: a comparison with other insect vectors of infectious diseases.

Human malaria, a major public health burden in tropical and subtropical countries, is transmitted exclusively by the bite of a female Anopheles mosquito. Malaria control strategies aimed at inducing sexual sterility in natural vector populations are an attractive alternative to the use of insecticides. However, despite their importance as disease vectors, limited information is available on the molecular mechanisms regulating fertility in Anopheles mosquitoes. In the major malaria vector, An. gambiae, the full complement of sperm and seminal fluid required for a female's lifelong egg production is obtained from a single mating event. This single mating has important consequences for the physiology and behavior of An. gambiae females: in particular, they become refractory to further insemination, and they start laying eggs. In other insects including Drosophila, similar post-copulatory changes are induced by seminal proteins secreted by the male accessory glands and transferred to the female during mating. In this review, we analyze the current state of knowledge on the function and characterization of male seminal proteins in An. gambiae, and provide a comparative assessment of the role of these male reproductive factors in other mosquito vectors of human disease in which female post-copulatory behavior has been studied. Knowledge of the factors and mechanisms regulating fertility in An. gambiae and other vectors can help the design of novel control strategies to fight the spread of disease.

Beginnings: a reflection on the history of gastrointestinal endocrinology.

The gut is the largest endocrine organ in the body. Gut hormones share some characteristics: Their structure groups hormones into families, each of which originate from a single gene. A hormone gene is often expressed in multiple peptides due to tandem genes, alternative splicing or differentiated posttranslational processing. By these mechanisms, more than 100 different hormonally active peptides are produced in the gastrointestinal tract. In addition, gut hormones are widely expressed outside the gut. The different cell types often express different products of the same gene and release the peptides in different ways. Consequently, the same peptide may act as a hormone, a local growth factor, or a neurotransmitter. This new biology suggests that gastrointestinal hormones should be conceived as intercellular messengers of major general impact. The following short review is a vignette on steps in the history of gastrointestinal endocrinology from classic studies of digestive juice secretion over peptide chemistry, immunochemistry, and molecular genetics to modern receptor pharmacology and drug development. From shadowy beginnings, gastrointestinal endocrinology has emerged as a central discipline in the understanding of multicellular life and its diseases.

Widespread expression of zinc transporter ZnT (SLC30) family members in mouse endocrine cells.

Zinc is abundant in most endocrine cell types, and plays a pivotal role in the synthesis and secretion of many hormones. Recent studies have demonstrated the expression of numerous zinc transporter (ZnT) family members in the pancreas, thyroid, and adrenal glands, suggesting a role for ZnTs in regulating cellular zinc homeostasis in endocrine cells. However, the cellular distribution of ZnTs in the endocrine organs has not been well established. In the present study, the mRNA expression level, cellular distribution of ZnTs as well as liable zinc ions were examined in the mouse pituitary, adrenal glands, thyroid, and pancreas. In general, ZnT1-10 mRNA was expressed to various degrees in the detected endocrine organs, with no detectable ZnT10 mRNA in the pancreas. In the anterior pituitary, both the acidophilic and basophilic cells were immunopositive to ZnT1-5, 7, 8, except for ZnT10. In the adrenal cortex, the immunoreactivity of all the tested ZnTs, including ZnT1-5, 7, 8, 10, was observed in the zona fasciculata, and some ZnTs were detected in the zona glomerulosa, zona reticularis, and the adrenal medulla. Both the follicle epithelial cells and parafollicular cells in the thyroid gland were immunostained with ZnT1-5, 7, 8, but not ZnT10. In the endocrine pancreas, the immunoreactivity of tested ZnTs was observed to various degrees except for ZnT10 in the cytoplasm of islet cells. Furthermore, autometallographic staining showed that liable zinc was observed in the endocrine cells, such as the adrenal cortical cells, thyroid follicle epithelial cells, and the pancreatic islet cells. All together, the wide distribution of liable zinc and the phenomenon that numerous ZnT family members are partially overlapped in a subset of endocrine cells suggest an important role for the ZnT family in controlling cellular zinc levels and subsequently regulating the synthesis and secretion of hormones in the endocrine system.

Identification and field evaluation of the sex pheromone of Synanthedon bicingulata (Staudinger).

The sex pheromone of Synanthedon bicingulata (Staudinger), a major pest of Prunus species in many regions of northeast Asia, was identified. Two major components from the pheromone gland extracts of female moths are (E,Z)-3,13-octadecadienyl acetate (E3,Z13-18:OAc) and (Z,Z)-3,13-octadecadienyl acetate (Z3,Z13-18:OAc), and the average ratio of these components is about 4:6, respectively. In addition to the major components, four minor components, (Z)-13-octadecenyl acetate (Z13-18:OAc), (E,Z)-2,13-octadecadienyl acetate (E2,Z13-18:OAc), (E,Z)-3,13-octadecadien-1-ol (E3,Z13-18:OH), and (Z,Z)-3,13-octadecadien-1-ol (Z3,Z13-18:OH) also were identified from pheromone gland extracts. Field tests showed that E3,Z13-18:OAc and Z3,Z13-18:OAc are essential for attraction of male S. bicingulata moths, and males are optimally attracted to the blend ratio found in pheromone gland extracts of conspecific females. Addition of the minor glandular components (Z13-18:OAc, E2,Z13-18:OAc, E3,Z13-18:OH, and Z3,Z13-18:OH) did not affect captures of males to the primary binary blend. Thus, the blend of E3,Z13-18:OAc and Z3,Z13-18:OAc at the natural ratio can be used for monitoring populations of this species.

Identification and field evaluation of the female sex pheromone of the sand Salix carpenterworm, Holcocerus arenicola Staudinger (Lepidoptera: Cossidae).

Extracts of female sex pheromone glands of the sand Salix carpenterworm moth, Holcocerus arenicola, a serious pest of desert thicket, were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Based on comparison of retention times and mass spectra of synthetic standards, four compounds were identified as cis-7-tetradecen-1-ol (Z7-14:OH), cis-5-tetradecen-1-yl acetate (Z5-14:OAc), cis-7-tetradecen-1-yl acetate (Z7-14:OAc), and cis-9-hexadecen-1-yl acetate (Z9-16:OAc) with the ratio of 24:39:100:43. Electroantennographic (EAG) analyses of these standard chemicals and their analogues showed that Z7-14:OAc elicited the largest male EAG response, followed by Z5-14:OAc and Z9-16:OAc. In field trials, traps baited with either Z7-14:OAc or Z5-14:OAc captured males while Z7-14:OH-, Z9-16:OAc- or solvent-baited traps caught no males. Z7-14:OAc as a single component was significantly more attractive than Z5-14:OAc alone. The combination of Z7-14:OAc and Z5-14:OAc showed an evidently synergistic effect and attracted much more males than the individual compounds in the field. Addition of Z7-14:OH to the blend of Z7-14:OAc and Z5-14:OAc enhanced slightly the trap catches. We conclude that the major components of the sex pheromone of H. arenicola are Z7-14:OAc and Z5-14:OAc. Currently, a triangle trap baited with the synthetic compounds Z7-14:OAc, Z5-14:OAc, and Z7-14:OH in a 1:0.4:0.25 ratio at 825 microg/trap dosage can be effectively used to monitor the H. arenicola population level and catch the males within the desert regions in China.

Identification and relative quantification of neuropeptides from the endocrine tissues.

Endocrine tissues like the pituitary, hypothalamus and islets of Langerhans are rich in bioactive peptides. These are used for intercellular signalling and are involved in regulation of almost all physiological processes. Peptidomics is the comprehensive analysis of peptides in tissues, fluids and cells. Peptidomics applied to (neuro-)endocrine tissues aims therefore to identify as many bioactive peptides as possible. Peptidomics of (neuro-)endocrine tissues requires an integrated approach that consists of careful sample handling, peptide separation techniques, mass spectrometry and bioinformatics. Here we describe the methods for isolation and dissection of endocrine tissues, the extraction of bioactive peptides and further sample handling and identification of peptides by mass spectrometry and hyphenated techniques. We also present a straightforward method for the comparison of relative levels of bioactive peptides in these endocrine tissues under varying physiological conditions. The latter helps to elucidate functions of the bioactive peptides.

Prothoracic gland semiochemicals of green lacewings.

Adult chrysopids have paired prothoracic glands (PG) that are thought to produce defensive secretions (allomones). We analyzed PG extracts of the following green lacewings from North and South America, Australia, and China: Ceraeochrysa cubana (Brazil); Chrysopa (= Co.) oculata, Co. nigricornis, Co. incompleta, Co. quadripunctata (USA), and Co. septempunctata (China); Chrysoperla (= Cl.) rufilabris (USA) and Cl. sp. (Brazil); Plesiochrysa ramburi and Mallada spp. (Australia). PG secretions are characteristic for species within a genus, except for Chrysopa spp. (Z)-4-Tridecene is ubiquitous, but (Z,Z)-4,7-tridecadiene is a major PG constituent in some Chrysopa spp. and in P. ramburi. Earlier reports that Co. oculata and Co. nigricornis produce 1-tridecene were shown to be in error. Chrysopa PG secretions are distinguished by the presence or absence of N-3-methylbutylacetamide, plus skatole (3-methylindole). Skatole is also identified for the first time from the Plesiochrysa and Ceraeochrysa. The PG secretion in Plesiochrysa ramburi is characterized by the presence of (Z)-4-undecene instead of (Z)-4-tridecene, and N-3-methylbutylpropanamide instead of the acetamide, resembling the PG secretions of Chrysopa nigricornis, Co. septempunctata and Co. incompleta. The chemotaxonomic value of PG semiochemicals is discussed, including evidence for subgroups within the genus Chrysopa as it now stands.

Identification and field bioassays of the sex pheromone of Synanthedon haitangvora.

Two major components from pheromone gland extracts of Synanthedon haitangvora females were identified as (Z,Z)-3,13-octadecadienyl acetate (Z3,Z13-18:OAc) and (E,Z)-2,13-octadecadienyl acetate (E2,Z13-18:OAc), and the average ratio of these components was about 1:1. Seven minor components, (Z)-9-hexadecenyl acetate (Z9-16:OAc), (Z)-11-hexadecenyl acetate (Z11-16:OAc), (Z)-9-octadecenyl acetate (Z9-18:OAc), (Z)-13-octadecenyl acetate (Z13-18:OAc), (E,Z)-3,13-octadecadienyl acetate (E3,Z13-18:OAc), (Z,Z)-3,13-octadecadien-1-ol (Z3,Z13-18:OH), and (E,Z)-2,13-octadecadien-1-ol (E2,Z13-18:OH), also were identified from gland extracts. Field tests showed that male S. haitangvora were attracted to Z3,Z13-18:OAc alone, but the maximum number of males was attracted to the binary blend of Z3,Z13-18:OAc and E2,Z13-18:OAc mimicking the blend found in female extracts. The addition of minor components to a 1:1 blend of Z3,Z13-18:OAc and E2,Z13-18:OAc did not increase the numbers of moths captured. The only significant effect of minor components was the strong inhibitory effect of adding Z3,Z13-18:OH to the primary binary blend. Increasing doses of the optimum pheromone blend in the lures from 0.1 to 2.0 mg increased trap catches of male S. haitangvora.

Expression of ghrelin and its receptor in human tissues.

Ghrelin is a peptide thought to be involved in the regulation of appetite. Furthermore, significant effects on the release of growth hormone (GH) and ACTH were demonstrated. Contributing to the physiological relevance of this hormone, we investigated the expression of ghrelin and its receptor (GHS-R) in several normal human tissues. RNA samples (BD Biosciences) underwent one-step TaqMan Real-Time RT-PCR. Immunohistochemistry was performed on paraffin-embedded tissues using specific primary antibodies against ghrelin and its receptor. Relevant ghrelin mRNA levels were detected in all human tissues with the highest levels in stomach, pituitary, and small intestine. By immunohistochemistry, ghrelin peptide expression was detectable in reproductive and endocrine organs (ovary, anterior pituitary, adrenal gland), and organs of the gastrointestinal tract (stomach, pancreas). GHS-R1a mRNA expression was demonstrated in 10 of 24 human organs analyzed with the highest levels in pituitary, adrenal gland, and spinal cord. Expression of the receptor peptide was detected by immunohistochemistry in endocrine and reproductive organs (anterior pituitary, thyroid, pancreas, testis), parts of the CNS (cerebrum, cerebellum), and in single cells of bone marrow. Expression of both ghrelin and its receptor in endocrine and reproductive organs may indicate new endocrine or paracrine mechanisms of regulation in these tissues.

Proteomic and bioinformatic analysis on endocrine organs of domesticated silkworm, Bombyx mori L. for a comprehensive understanding of their roles and relations.

Three organs of silkworm larva endocrine system, including brain (Br), subesophageal ganglion (SG) and prothoracic glands (PG), were studied employing shotgun LC-MS/MS combined with bioinformatic analysis to comprehensively understand their roles and relations. Totally, 3430, 2683, and 3395 proteins were identified including 1885 common and 652, 253, and 790 organ-specific ones in Br, SG, and PG, respectively. Identified common-expressed proteins indicated the existence of intrinsic complex interactions among these parts of endocrine system. Most of the reputed organs-specific proteins were identified by this approach. KEGG pathway analysis showed 162 same pathways among the 169, 164, and 171 relating Br, SG, and PG. This analysis revealed functional similarities with exceptional resemblance in their metabolism and signaling pathways of the three organs. On the other hand, 70, 57, and 114 organ-specific enzymes related pathways were detected for Br, SG, and PG confirming their functional differences. These results reveal a cooperative mechanism among the three endocrine organs in regulating various physiological and developmental events, and also suggest that the organ-specific proteins might be the fundamental factors responsible for the functional differentiation of these organs.

Precerebellin-related genes and precerebellin 1 peptide in endocrine glands of the rat - pattern of their expression.

The hexadecapeptide cerebellin (CER) is derived from a larger protein, cerebellin 1 precursor protein (Cbln1). At present four precerebellins (Cbln1-4) are known. They are highly expressed in the brain, in particular in the cerebellum. Since CER is involved in regulating endocrine functions, present studies aimed to investigate, by means of molecular biology techniques (RT-PCR, QPCR, Western blotting) the expression of Cbln related genes and Cbln1 protein in classic endocrine glands of the rat. RT-PCR revealed the presence of Cbln1 and Cbln3 mRNAs in all endocrine glands tested; hypothalamus, anterior pituitary, thyroid, adrenal cortex, testis, ovary and pancreatic islets. Expression of Cbln2 gene was demonstrated only in the hypothalamus, anterior pituitary and adrenal cortex and in cerebral cortex, which was studied as a positive control organ. On the contrary, expression of Cbln4 gene was found only in the cerebral cortex. Using QPCR, the highest expression of Cbln1 gene was demonstrated in hypothalamus and pancreatic islets, a somewhat lower one in the anterior pituitary and thyroid, while the lowest was in adrenal cortex, testis and ovary. In general, the Cbln3 gene exhibited a similar pattern of expression, with the highest level in pancreatic islets and somewhat lower in the hypothalamus. Cbln2 gene expression was high in the hypothalamus, lower in the anterior pituitary and very low in adrenal cortex. In general, the pattern of Cbln1 protein expression was similar to that of Cbln1 mRNA. Further experiments aimed to check possible association of Cbln1 with cell membrane. Such association is suggested by differences in Cbln1 protein amount after extraction with RIPA and TRIS buffers. Bioinformatic methods predicting transmembrane topology (HMMTOP and SPLIT 4.0 servers) suggest transmembrane localisation of Cbln1, with transmembrane domain sequence responsible for the formation of an alpha-helix. These findings suggest possible physiological roles of Cbln related peptides not only in the cerebellum, but also in the endocrine system. However, their specific role as modulators of the endocrine system requires further investigations.

Disposition and metabolic profiling of [14C]-decabromodiphenyl ether in pregnant Wistar rats.

Fully brominated diphenyl ether, decabromodiphenyl ether (DBDE), is one of the most widely used brominated flame retardants worldwide. Little data is available about the metabolic fate of DBDE in animal models and nothing at all about the extent of foetal exposure. In this work, pregnant Wistar rats were force-fed with 99.8% pure [14C]-DBDE over 96 h at a late stage of gestation (days 16 to 19). More than 19% of the administered dose was recovered in tissues and carcasses, demonstrating efficient absorption of DBDE despite its high molecular weight and low solubility. The highest concentrations of DBDE residues were found in endocrine glands (adrenals, ovaries) and in the liver, with lower values recorded for fat. In all tissue extracts, most of the radioactivity was associated with unchanged DBDE. The use of high-grade purity [14C]-DBDE allowed quantification of several metabolites present both in maternal tissues and in foetuses. These biotransformation products accounted for 9-27% of the extractable radioactivity in tissues and 14% of that in foetuses. Three nona-BDEs and one octa-BDE were identified by LC-APPI/MS. The unequivocal characterisation of a hydroxylated octa-BDE isolated from liver was confirmed by NMR. In rat, the main metabolic pathways of DBDE are debromination and oxidation. DBDE, and very likely most of its metabolites, are able to cross the placental barrier in rat. Metabolic profiles, obtained in vivo for the first time, demonstrated the presence of DBDE and major biotransformation products in endocrine glands as well as in foetuses. The biological activity of these metabolites still needs to be assessed in order to better understand the potential toxicity of DBDE.

Effect of retinoic acid on hemolymph glucose regulation in the fresh water edible crab Oziotelphusa senex senex.

9-cis-Retinoic acid (9CRA) and all-trans-retinoic acid (ATRA) are known to be involved in the regulation of glucose homeostasis in vertebrates by inducing insulin release and expression of glucose reporter proteins. In view of the fact that 9CRA and ATRA are endogenous in crustaceans and a retinoic acid X-receptor exists in crabs, we investigated whether 9CRA and ATRA also plays a role in glucose homeostasis in freshwater crab, Oziotelphusa senex senex. Injection of 9CRA into intact crabs significantly increased the hemolymph glucose level in a dose-dependent manner. Such 9CRA-induced hyperglycemia was apparently mediated by the CHH since injection of 9CRA into eyestalk-ablated crabs did not result in hyperglycemia. In support of this, administration of 9CRA in to crabs resulted in reduced hyperglycemic activity of eyestalks and elevated titers of CHH in hemolymph. ATRA injection did not cause any changes in hemolymph glucose and CHH levels. The results provide the first evidence that 9-cis-retinoic acid, but not all-trans-retinoic acid, is involved in the regulation of glucose homeostasis and apparently mediated by the eyestalk hormone CHH.

Improved cleanup technique for gas chromatographic-mass spectrometric determination of alkylphenols from biota extract.

A simple and economical cleanup technique was developed to determine alkylphenols by GC-MS from biological extracts containing relatively high lipids. The lipids were successfully removed from bivalve extracts through a two-step cleanup. The new method is a combination of Florisil adsorption chromatography and silyl derivatization technique. Low and high (non-polar and highly polar) molecular weight lipids were removed from the biota extract with deactivated Florisil column in the first step. And in the second step, middle molecular weight (middle polar) lipids were removed in an activated Florisil column after the alkylphenols were converted to corresponding silyl derivatives with bis(trimethylsilyl)trifluoroacetamide (BSTFA). On the basis of the above results, a simple cleanup kit was developed for convenience. The technique was optimized with reference to the activity of packing materials and polarity of eluting solvents. Only 3g of Florisil, 25 mL of hexane and 10 mL of dichloromethane were required for one sample. The recoveries of alkylphenols from spiked samples varied from 88 to 103% with a low relative standard deviation (mean value: 5.3%) and the recovery was similar or even higher than other methods currently in use. The technique was successfully applied to mussel samples from Masan Bay, South Korea. Simultaneous measurement of these compounds in water, sediment and biota; the resulting bio-concentration factor and their relationships confirm previously published works, validating the method applied.

The universal algorithm of maturation for secretory and excretory protein precursors.

During maturation, most proteins undergo different posttranslational modifications. In most simple cases, signal peptidases remove the signal or leader peptide from the precursors of the secretory proteins during their translocation across the ER membrane. For biologically active proteins, such as enzymes, regulatory and defense proteins, toxins, etc., additional maturation-regulating mechanisms were shown to proceed with limited proteolysis of inactive precursors by specific enzymes. A number of specific enzymes from different cell types selectively cleave proproteins at specific processing sites. In this work, we analyzed the sequences of protein precursors synthesized in the excretory glands of different animals and identified new, non-traditional processing sites. They differ from the motifs previously identified in secreted proteins' precursors and enabled us to reconstruct the sequence of events leading to the conversion of protein precursors into the final products (mature proteins). We also found that in animals, the maturation mechanism of secretory and excretory proteins and the set of enzymes involved are species specific. The processing sites identified in protein precursors in this study are useful for a more detailed genome analysis and more accurate mature protein sequence prediction.

Cellular expression of Noc2, a Rab effector protein, in endocrine and exocrine tissues in the mouse.

Noc2 is a Rab effector which participates in regulated exocytosis. It is expressed abundantly in endocrine cells but at low levels in exocrine tissues. Noc2-deficient mice, however, exhibit marked accumulation of secretory granules in exocrine cells rather than endocrine cells. In the present study, we investigated localization of Noc2 immunohistochemically in various endocrine and exocrine tissues in normal mice. Western blotting detected a Noc2-immunoreactive band of 38 kDa in isolated pancreatic islets, the adrenal gland, pituitary gland, and thyroid gland. Immunostaining for Noc2 labeled endocrine cells in the adrenal medulla and adenohypophysis, pancreatic islet cells, thyroid parafollicular cells, and gut endocrine cells, supporting the notion that Noc2 is a Rab effector protein shared by amine/peptide-secreting endocrine cells. Besides endocrine tissues, granular ducts in salivary glands contained Noc2. Although immunostaining failed to detect Noc2 in acinar cells of all exocrine glands examined, reverse transcriptase-polymerase chain reaction analysis detected the mRNA expression in exocrine pancreas. Ultrastructurally, Noc2 immunoreactivity was associated with the limiting membrane of granules in both pancreatic endocrine and salivary duct exocrine cells. The cellular and subcellular localizations of Noc2 should yield key information on its functional significance as well as account for the phenotype in Noc2-deficient mice.

Helicobacter pylori infection stimulates intestinalization of endocrine cells in glandular stomach of Mongolian gerbils.

Intestinal metaplasia has been investigated extensively as a possible premalignant condition for stomach cancer but its pathogenesis is still not fully understood. In the present study, we examined the relationship between endocrine and mucous cell marker expression periodically after Helicobacter pylori infection in the Mongolian gerbil model. The numbers of chromogranin A (CgA)-positive, gastrin-positive and gastric inhibitory polypeptide (GIP)-positive cells in H. pylori-infected groups was increased significantly compared with the non-infected case. However, CgA-positive and gastrin-positive cells then decreased from 50 through 100 experimental weeks after H. pylori infection, whereas GIP-positive cells increased. Coexistence of gastrin-positive and GIP-positive cells was detected in the same gastric and intestinal mixed phenotypic glandular-type glands. In conclusion, the endocrine cell phenotype is in line with that of the mucous counterpart in the glands of H. pylori-infected Mongolian gerbil stomach, supporting the concept that development of intestinal metaplasia is due to the abnormal differentiation of a stem cell.

Cellular localization of PRL-1 and PRL-2 gene expression in normal adult human tissues.

Recent evidence suggests that the PRL-1 and -2 phosphatases may be multifunctional enzymes with diverse roles in a variety of tissue and cell types. Northern blotting has previously shown widespread expression of both transcripts; however, little is known about the cell type-specific expression of either gene, especially in human tissues. Therefore, we investigated expression patterns for PRL-1 and -2 genes in multiple normal, adult human tissues using in situ hybridization. Although both transcripts were ubiquitously expressed, they exhibited strikingly different patterns of expression. PRL-2 was expressed heavily in almost every tissue and cell type examined, whereas PRL-1 expression levels varied considerably both between tissue types and between individuals. Widespread expression of PRL-1 and -2 in multiple organ systems suggests an important functional role for these enzymes in normal tissue homeostasis. In addition, the variable patterns of expression for these genes may provide distinct activities in each tissue or cell type.