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Sample records for hormones gastrin sth

  1. Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle.

    PubMed

    Zhao, Hongqiong; Yannaing, Swe; Thanthan, Sint; Kuwayama, Hideto

    2011-11-01

    This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 μg/kg BW of [D-Lys(3)]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from -10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 μg/kg was weaker than that of 4.0 μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [D-Lys(3)]-GHRP-6; however, [D-Lys(3)]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.

  2. NF-kappaB mediated transcriptional repression of acid modifying hormone gastrin.

    PubMed

    Datta De, Dipanjana; Datta, Arindam; Bhattacharjya, Sumana; Roychoudhury, Susanta

    2013-01-01

    Helicobacter pylori is a major pathogen associated with the development of gastroduodenal diseases. It has been reported that H. pylori induced pro-inflammatory cytokine IL1B is one of the various modulators of acid secretion in the gut. Earlier we reported that IL1B-activated NFkB down-regulates gastrin, the major hormonal regulator of acid secretion. In this study, the probable pathway by which IL1B induces NFkB and affects gastrin expression has been elucidated. IL1B-treated AGS cells showed nine-fold activation of MyD88 followed by phosphorylation of TAK1 within 15 min of IL1B treatment. Furthermore, it was observed that activated TAK1 significantly up-regulates the NFkB subunits p50 and p65. Ectopic expression of NFkB p65 in AGS cells resulted in about nine-fold transcriptional repression of gastrin both in the presence and absence of IL1B. The S536A mutant of NFkB p65 is significantly less effective in repressing gastrin. These observations show that a functional NFkB p65 is important for IL1B-mediated repression of gastrin. ChIP assays revealed the presence of HDAC1 and NFkB p65 along with NCoR on the gastrin promoter. Thus, the study provides mechanistic insight into the IL1B-mediated gastrin repression via NFkB.

  3. Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter.

    PubMed

    Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2014-02-01

    Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn(2)(+) ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55 ± 14-fold at 100 μM (P<0.05). Significant stimulation was also observed with Cd(2)(+) and Cu(2)(+), but not with Ca(2)(+), Mg(2)(+), Ni(2)(+), or Fe(3)(+) ions. Activation of MAPK and phosphatidylinositol 3-kinase pathways is necessary but not sufficient for gastrin induction by Zn(2)(+). Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn(2)(+)-dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial-mesenchymal transition (EMT), together with our observation that Zn(2)(+) ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn(2)(+) ions may induce an EMT, and that gastrin may be involved in the transition.

  4. [Synthesis of peptides with gastrinlike activity. Studies on the structure-activity relationship of the natural hormone human little gastrin I].

    PubMed

    Göhring, W; Moroder, L; Borin, G; Lobbia, A; Bali, J P; Wünsch, E

    1984-01-01

    To identify the role of the block of glutamic acid residues characteristic for the gastrin molecule, a series of shortened peptides related to the human little-gastrin-I sequence were synthesized. The biological activities of these gastrin peptides strongly suggest in the pentaglutamic acid sequence a specific information for a pronounced amplification of the hormonal activity.

  5. Gastrins and gastrinomas.

    PubMed Central

    Hansky, J.

    1984-01-01

    The past 20 years have seen gastrin attain true hormonal status. Its structure has been characterized, it has been synthesized, radioimmunoassays for its measurement in blood and tissues have been developed and its physiology and metabolism elucidated. Of much interest to clinicians has been the association between gastrin and tumours of the pancreas (gastrinomas) and atrophic gastritis. The advent of gastrin measurement has facilitated the diagnosis of gastrinoma and the availability of powerful acid suppressants has altered the therapy of gastrinoma. PMID:6390404

  6. Gastrins, iron and colorectal cancer.

    PubMed

    Baldwin, Graham S

    2009-09-01

    This minireview explores the connections between circulating gastrins, iron status and colorectal cancer. The peptide hormone gastrin is a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. Gastrins bind two ferric ions with μM affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity. The ferric ion ligands have been identified as glutamates 7, 8 and 9 in the 18 amino acid peptide glycine-extended gastrin. An interaction between gastrin and transferrin was first demonstrated by covalent crosslinking techniques, and has been recently confirmed by surface plasmon resonance. We have therefore proposed that gastrins act as catalysts in the loading of transferrin with iron. Several recent lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease haemochromatosis, and that transferrin saturation positively correlates with circulating gastrin concentrations, suggest that gastrins may be involved in iron homeostasis. In addition the recognition that ferric ions may play an unexpected role in the biological activity of non-amidated gastrins may assist in the development of new therapies for colorectal carcinoma.

  7. Novel roles of gastrin.

    PubMed

    Dimaline, Rod; Varro, Andrea

    2014-07-15

    The existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as plasminogen activator inhibitors and matrix metalloproteinases that have important actions on extracellular matrix remodelling. These actions are, at least in part, effected by paracrine signalling pathways and make important contributions to maintaining functional integrity of the gastric epithelium. Recent studies also provide support for the idea that gastrin, in concert with other hormones, could potentially contribute a post-prandial incretin effect. We also review recent developments in the biology of other gastrin gene products, including the precursor progastrin, which causes proliferation of the colonic epithelium and in certain circumstances may induce cancer formation. Glycine-extended biosynthetic processing intermediates also have proliferative effects in colonic mucosa and in some oesophageal cancer cell lines. Whether these additional gene products exert their effects through the CCK2 receptor or a separate entity is currently a matter of debate.

  8. Gastrins, iron homeostasis and colorectal cancer.

    PubMed

    Kovac, Suzana; Anderson, Gregory J; Baldwin, Graham S

    2011-05-01

    The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron deficiency anemia was recognized as a long-term consequence of partial gastrectomy. This review summarizes the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyze the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

  9. Gastrins, Iron Homeostasis and Colorectal Cancer

    PubMed Central

    Kovac, Suzana; Anderson, Gregory J.; Baldwin, Graham S.

    2011-01-01

    The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron-deficiency anemia was recognised as a long-term consequence of partial gastrectomy. This review summarises the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron-binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyse the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron-overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. PMID:21320535

  10. Gastrin-induced proliferation involves MEK partner 1 (MP1).

    PubMed

    Steigedal, Tonje S; Prestvik, Wenche S; Selvik, Linn-Karina M; Fjeldbo, Christina S; Bruland, Torunn; Lægreid, Astrid; Thommesen, Liv

    2013-03-01

    The peptide hormone gastrin is an important factor for the maintenance and homeostasis of the gastric mucosa. We show that gastrin stimulates proliferation in a dose-dependent manner in the human gastric adenocarcinoma cell line AGS-GR. Furthermore, we demonstrate that the MAPK scaffold protein MEK partner 1 (MP1) is important for gastrin-induced phosphorylation of ERK1 and ERK2 and that MP1 promotes gastrin-induced proliferation of AGS-GR cells. Our results suggest a role of MP1 in gastrin-induced cellular responses involved in proliferation and homeostasis of the gastric mucosa.

  11. Role of gastrin-peptides in Barrett's and colorectal carcinogenesis.

    PubMed

    Chueca, Eduardo; Lanas, Angel; Piazuelo, Elena

    2012-12-07

    Gastrin is the main hormone responsible for the stimulation of gastric acid secretion; in addition, gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types. Gastrin synthesis and secretion are increased in certain situations, for example, when proton pump inhibitors are used. The impact of sustained hypergastrinemia is currently being investigated. In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates; although, this relationship is less clear in human beings. Higher gastrin levels have been shown to cause hyperplasia of several cell types; yet, the risk for developing cancer seems to be the same in normo- and hypergastrinemic patients. Some tumors also produce their own gastrin, which can act in an autocrine manner promoting tumor growth. Certain cancers are extremely dependent on gastrin to proliferate. Initial research focused only on the effects of amidated gastrins, but there has been an interest in intermediates of gastrin in the last few decades. These intermediates aren't biologically inactive; in fact, they may exert greater effects on proliferation and apoptosis than the completely processed forms. In certain gastrin overproduction states, they are the most abundant gastrin peptides secreted. The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production, levels, and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.

  12. Gastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor.

    PubMed

    Kovac, Suzana; Xiao, Lin; Shulkes, Arthur; Patel, Oneel; Baldwin, Graham S

    2010-11-05

    The involvement of the gastrointestinal hormone gastrin in the development of gastrointestinal cancer is highly controversial. Here we demonstrate a positive-feedback loop whereby gastrin, acting via the CCK2 receptor, increases its own expression. Such an autocrine loop has not previously been reported for any other gastrointestinal hormone. Gastrin promoter activation was dependent on the MAP kinase pathway and did not involve Sp1 binding sites or epidermal growth factor receptor transactivation. As the treatment of gastrointestinal cancer cells with amidated gastrin led to increased expression of non-amidated gastrins, the positive-feedback loop may contribute to the sustained increase in circulating gastrins observed in colorectal cancer patients.

  13. Serum gastrin level in early childhood.

    PubMed Central

    Sann, L; Chayvialle, A P; Bremond, A; Lambert, R

    1975-01-01

    Serum gastrin concentration was measured in newborns and infants with no gastrointestinal disorders, in the fasting state and after food stimulation. Mean fasting concentration in 14 newborns aged 1 to 12 days (130 . 4 pg/ml +/- 11 . 4 SE) was significantly higher than the mean value in 23 infants aged 1.5 to 22 months (101.4 +/- 6.6 pg/ml). Ingestion of the usual milk meal resulted in a definite rise of the serum gastrin level in the 5 subjects tested (3 newborns and 2 infants). The mean fasting serum gastrin level in 6 babies with hiatus hernia and gastro-oesophageal reflux was found to be no different from the corresponding value in 8 age-matched controls. However, a conspicuously raised fasting gastrin concentration was observed in one infant with lower oesophageal dyskinesia. The results indicate that the release of gastrin and the reactivity of the hormone-producing sites to food stimulation in early life are similar to those in adult humans. No defect of gastrin release was shown in patients with gastro-oesophageal reflux. PMID:1244175

  14. Gastrin and gastric surgery.

    PubMed

    Fabri, P J; McGuigan, J E

    1976-01-01

    The development of the radioimmunoassay for gastrin has resulted in significant increases in our knowledge of the physiology of the stomach and antrum, and in an objective recognition of the interaction of the gastrin and vagus mechanisms. Recent identification of multiple species of gastrin in the circulation, however, raises questions as to the significance of early experimental results. Until the various aspects of gastrin and their relative contributions in the normal state and in pathologic processes are identified, the significance of gastrin levels in the evaluation of patients with uncomplicated ulcer disease is unclear. Although many investigators have attempted to correlate changes in serum gastrin levels in response to various stimuli with the completeness of vagotomy or the likelihood of recurrence, it is too early to give any clinical significance to these reports. Several points in particular seem worthy of emphasis: 1. Preoperative serum gastrin levels are currently of no value in selecting an operation for the treatment of duodenal ulcer disease. 2. The difference in serum gastrin levels in response to feeding that may be shown to exist between groups of normal subjects and duodenal ulcer patients is not a value in diagnosing ulcer disease in a specific patient, nor in differentiating duodenal ulcer from other conditions. 3. The measurement of serum gastrin levels in association with Hollander tests, while perhaps of potential future benefit, does not improve the accuracy of the Hollander test nor do results necessarily relate to vagal innervation. 4. Postoperative serum gastrin levels are increased after vagotomy. The degree of hypergastrinemia after vagotomy does not correlate with risk of ulcer recurrence. 5. Hypergastrinemia (greater than 1000 pg. per ml.) in the presence of hyperacidity is essentially pathognomonic of the Zollinger-Ellison syndrome. Calcium and secretin infusions do not add to the diagnosis if clear-cut clinical and laboratory

  15. The art of measuring gastrin in plasma: a dwindling diagnostic discipline?

    PubMed

    Rehfeld, Jens F

    2008-01-01

    The gastrointestinal hormone gastrin is measured in plasma in physiological, pathophysiological and diagnostic investigations. In the diagnosis of hypergastrinaemic diseases such as gastrinomas and gastric achlorhydria, measurement of gastrin concentrations in circulation is crucial. Gastrin circulates, however, not as a single peptide but as a mixture of peptides of different lengths and amino acid derivatizations. Moreover, in hypergastrinaemia the peptide pattern changes. Consequently, diagnostic gastrin measurements require immunoassays that recognize the pathological plasma patterns, which are characterized by a predominance of the large peptides (gastrin-34 and gastrin-71) and less, if any, of the shorter main form of gastrin in normal tissue, gastrin-17. Alternatively, and in specific cases, "processing-independent assays" (PIA) for progastrin may be considered, since hypersecreting gastrin cells also release substantial amounts of biosynthetic precursors and processing intermediates. Recently, gastrin kits that do not take the pathological plasma patterns into account have been marketed and may miss the diagnosis. Therefore, proper diagnosis of gastrinomas and other hypergastrinaemic diseases requires insight into cellular gastrin synthesis and peripheral metabolism, and also into the design of useful immunoassays. This review discusses the art of measuring gastrin in plasma with adequate diagnostic specificity.

  16. Gastrin blood test

    MedlinePlus

    ... doctor. Medicines that can increase gastrin measurements include antacids, H 2 -blocking agents (such as cimetidine), and ... Helicobacter pylori infection of the stomach Use of antacids or medicines to treat heartburn Zollinger-Ellison syndrome , ...

  17. Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas.

    PubMed

    Suissa, Yaron; Magenheim, Judith; Stolovich-Rain, Miri; Hija, Ayat; Collombat, Patrick; Mansouri, Ahmed; Sussel, Lori; Sosa-Pineda, Beatriz; McCracken, Kyle; Wells, James M; Heller, R Scott; Dor, Yuval; Glaser, Benjamin

    2013-01-01

    Neurogenin3(+) (Ngn3(+)) progenitor cells in the developing pancreas give rise to five endocrine cell types secreting insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Gastrin is a hormone produced primarily by G-cells in the stomach, where it functions to stimulate acid secretion by gastric parietal cells. Gastrin is expressed in the embryonic pancreas and is common in islet cell tumors, but the lineage and regulators of pancreatic gastrin(+) cells are not known. We report that gastrin is abundantly expressed in the embryonic pancreas and disappears soon after birth. Some gastrin(+) cells in the developing pancreas co-express glucagon, ghrelin or pancreatic polypeptide, but many gastrin(+) cells do not express any other islet hormone. Pancreatic gastrin(+) cells express the transcription factors Nkx6.1, Nkx2.2 and low levels of Pdx1, and derive from Ngn3(+) endocrine progenitor cells as shown by genetic lineage tracing. Using mice deficient for key transcription factors we show that gastrin expression depends on Ngn3, Nkx2.2, NeuroD1 and Arx, but not Pax4 or Pax6. Finally, gastrin expression is induced upon differentiation of human embryonic stem cells to pancreatic endocrine cells expressing insulin. Thus, gastrin(+) cells are a distinct endocrine cell type in the pancreas and an alternative fate of Ngn3+ cells.

  18. Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration.

    PubMed

    Kumar, J Dinesh; Steele, Islay; Moore, Andrew R; Murugesan, Senthil V; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea; Dockray, Graham J

    2015-07-15

    The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling.

  19. GASTRIN, INFLAMMATION, AND CARCINOGENESIS

    PubMed Central

    Chao, Celia; Hellmich, Mark R.

    2014-01-01

    Purpose of review Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model represents the prototypical inflammation-associated cancer. In this review, we present the latest clinical and experimental evidence showing that gastrin peptides and their receptors (the cholecystokinin [CCK2] receptors) potentiate the progression of gastric cancer and other gastrointestinal malignancies in the presence of inflammation. Recent Findings We highlight the feed-forward mechanisms by which gastrin and CCK2 receptor expression are upregulated during inflammation and in GI cancers, summarize gastrin’s pro-inflammatory role by inducing the production cyclooxgenase-2 (COX-2) and interleukin-8 (IL-8), and relate evidence suggesting that gastrin and their receptors modulate the function of immune cells and fibroblasts following cellular stress, injury, repair, as well as during cancer progression. Summary We discuss trends for future studies directed toward the elucidation of gastrin peptides’ role in regulating inter-cellular molecular signaling mechanisms between local and circulating immune cells, fibroblasts, epithelial cells, and other cell-types in the microenvironments of inflammation-related cancers. Elucidation of the molecular and cellular pathways that relate inflammation with cancer may provide additional opportunities to develop complementary therapies that target the inflammatory microenvironment of the cancer. PMID:19907321

  20. Gastrin: The Test

    MedlinePlus

    ... services. Advertising & Sponsorship: Policy | Opportunities PLEASE NOTE: Your web browser does not have JavaScript enabled. Unless you enable Javascript , your ability to navigate and access the features of this website will be ... Share this page: Was this page helpful? Formal name: Gastrin Related tests: Helicobacter pylori , Gastric Acid At a Glance Test ...

  1. Chinchilla "big" and "little" gastrins.

    PubMed

    Shinomura, Y; Eng, J; Yalow, R S

    1987-02-27

    Gastrin heptadecapeptides (gastrins I and II which differ in the presence of sulfate on the tyrosine of the latter) have been purified and sequenced from several mammalian species including pig, dog, cat, sheep, cow, human and rat. A 34 amino acid precursor ("big" gastrin), generally accounting for only 5% of total gastrin immunoreactivity, has been purified and sequenced only from the pig, human, dog and goat. Recently we have demonstrated that guinea pig (GP) "little" gastrin is a hexadecapeptide due to a deletion of a glutamic acid in the region 6-9 from its NH2-terminus and that GP "big" gastrin is a 33 amino acid peptide. The chinchilla, like the GP, is a New World hystricomorph. This report describes the extraction and purification of "little" and "big" gastrins from 31 chinchilla antra. Chinchilla "little" gastrin is a hexadecapeptide with a sequence identical to that of the GP and its "big" gastrin is a 33 amino acid peptide with the following sequence: (See text)

  2. Identification of ezrin as a target of gastrin in immature mouse gastric parietal cells.

    PubMed

    Pagliocca, Adelina; Hegyi, Peter; Venglovecz, Viktoria; Rackstraw, Stephen A; Khan, Zara; Burdyga, Galina; Wang, Timothy C; Dimaline, Rod; Varro, Andrea; Dockray, Graham J

    2008-11-01

    The gastric acid-secreting parietal cell exhibits profound morphological changes on stimulation. Studies in gastrin null (Gas-KO) mice indicate that maturation of parietal cell function depends on the hormone gastrin acting at the G-protein-coupled cholecystokinin 2 receptor. The relevant cellular mechanisms are unknown. The application of differential mRNA display to samples of the gastric corpus of wild-type (C57BL/6) and Gas-KO mice identified the cytoskeletal linker protein, ezrin, as a previously unsuspected target of gastrin. Gastrin administered in vivo or added to gastric glands in vitro increased ezrin abundance in Gas-KO parietal cells. In parietal cells of cultured gastric glands from wild-type mice treated with gastrin, histamine or carbachol, ezrin was localized to vesicular structures resembling secretory canaliculi. In contrast, in cultured parietal cells from Gas-KO mice, ezrin was typically distributed in the cytosol, and this did not change after incubation with gastrin, histamine or carbachol. However, priming with gastrin for approximately 24 h, either in vivo prior to cell culture or by addition to cultured gastric glands, induced the capacity for secretagogue-stimulated localization of ezrin to large vesicular structures in Gas-KO mice. Similarly, in a functional assay based on measurement of intracellular pH, cultured parietal cells from Gas-KO mice were refractory to gastrin unless primed. The priming effect of gastrin was not attributable to the paracrine mediator histamine, but was prevented by inhibitors of protein kinase C and transactivation of the epidermal growth factor receptor. We conclude that in gastrin null mice there is reduced ezrin expression and a defect in ezrin subcellular distribution in gastric parietal cells, and that both can be reversed by priming with gastrin.

  3. Recent improvements on micro-thermocouple based SThM

    NASA Astrophysics Data System (ADS)

    Nguyen, TP; Thiery, L.; Teyssieux, D.; Briand, D.; Vairac, P.

    2017-01-01

    The scanning thermal microscope (SThM) has become a versatile tool for local surface temperature mapping or measuring thermal properties of solid materials. In this article, we present recent improvements in a SThM system, based on a micro-wire thermocouple probe associated with a quartz tuning fork for contact strength detection. Some results obtained on an electrothermal micro-hotplate device, operated in active and passive modes, allow demonstrating its performance as a coupled force detection and thermal measurement system.

  4. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides.

    PubMed

    Rehfeld, J F

    2011-04-01

    Gastrin and cholecystokinin (CCK) are homologous hormone systems known to regulate gastric acid secretion, gallbladder emptying, and cell growth in the pancreas and stomach. They are, however, also involved in the development and secretory functions of pancreatic islet cells. For instance, foetal and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man. Accordingly, endogenous hypergastrinaemia is accompanied by islet cell hyperplasia and increased insulin secretion. Conventionally, the effect of gastrointestinal hormones on insulin secretion (the incretin effect) has been defined and quantified in relation to oral versus intravenous glucose loadings. Under these unphysiological conditions, the release of gastrin and CCK and, hence, their effect on insulin secretion are modest in comparison with the effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1). Consequently, the interest of CCK and gastrin in incretin research has for decades been limited. A few years ago, however, it was suggested that gastrin together with epidermal growth factor or later GLP-1 might stimulate beta cell growth and secretion. Recent studies have shown that the combination of gastrin and GLP-1 actually restores normoglycaemia in diabetic mice. Therefore, a short review of the incretin system in a broader functional context that includes gastrin and CCK peptides may be timely.

  5. Gastrin and Gastric Cancer

    PubMed Central

    Waldum, Helge L.; Sagatun, Liv; Mjønes, Patricia

    2017-01-01

    Gastric cancer although occurring in reduced frequency is still an important disease, partly because of the bad prognosis when occurring in western countries. This decline in occurrence may mainly be due to the reduced prevalence of Helicobacter pylori (Hp) infection, which is the most important cause of gastric cancer. There exist many different pathological classifications of gastric carcinomas, but the most useful seems to be the one by Lauren into intestinal and diffuse types since these types seldom transform into the other and also have different epidemiology. During the nearly 30 years that have passed since the groundbreaking description of Hp as the cause of gastritis and gastric cancer, a continuous search for the mechanism by which Hp infection causes gastric cancer has been done. Interestingly, it is mainly atrophic gastritis of the oxyntic mucosa that predisposes to gastric cancer possibly by inducing hypoacidity and hypergastrinemia. There are many arguments in favor of an important role of gastrin and its target cell, the enterochromaffin-like cell, in gastric carcinogenesis. The role of gastrin in gastric carcinogenesis implies caution in the long-term treatment with inhibitors of gastric acid secretion inducing secondary hypergastrinemia, in a common disease like gastroesophageal reflux disease. PMID:28144230

  6. High Affinity Binding of Indium and Ruthenium Ions by Gastrins.

    PubMed

    Baldwin, Graham S; George, Graham N; Pushie, M Jake

    2015-01-01

    The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga3+ were fitted by a 2 site model with dissociation constants (Kd) of 3.3 x 10-7 and 1.1 x 10-6 M. Although the absorption of gastrin did not change upon the addition of In3+ ions, the changes in absorbance on Fe3+ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In3+ of 6.5 x 10-15 and 1.7 x 10-7 M. Similar results were obtained with Ru3+ ions, although the Kd values for Ru3+ of 2.6 x 10-13 and 1.2 x 10-5 M were slightly larger than observed for In3+. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0-3.3 Å, the Ru complex clearly demonstrated a short range Ru-Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In3+ or Ru3+ ions, and that the affinity of the first site for In3+ or Ru3+ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy.

  7. NR4A2 Is Regulated by Gastrin and Influences Cellular Responses of Gastric Adenocarcinoma Cells

    PubMed Central

    Misund, Kristine; Selvik, Linn-Karina Myrland; Rao, Shalini; Nørsett, Kristin; Bakke, Ingunn; Sandvik, Arne K.; Lægreid, Astrid; Bruland, Torunn; Prestvik, Wenche S.; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells. PMID:24086717

  8. NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells.

    PubMed

    Misund, Kristine; Selvik, Linn-Karina Myrland; Rao, Shalini; Nørsett, Kristin; Bakke, Ingunn; Sandvik, Arne K; Lægreid, Astrid; Bruland, Torunn; Prestvik, Wenche S; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells.

  9. Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration

    PubMed Central

    Kumar, J. Dinesh; Steele, Islay; Moore, Andrew R.; Murugesan, Senthil V.; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D. Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea

    2015-01-01

    The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling. PMID:25977510

  10. An OmpA-Like Protein from Acinetobacter spp. Stimulates Gastrin and Interleukin-8 Promoters

    PubMed Central

    Ofori-Darko, Ernest; Zavros, Yana; Rieder, Gabriele; Tarlé, Susan A.; Van Antwerp, Mary; Merchant, Juanita L.

    2000-01-01

    Bacterial overgrowth in the stomach may occur under conditions of diminished or absent acid secretion. Under these conditions, secretion of the hormone gastrin is elevated. Alternatively, bacterial factors may directly stimulate gastrin. Consistent with this hypothesis, we found that mice colonized for 2 months with a mixed bacterial culture of opportunistic pathogens showed an increase in serum gastrin. To examine regulation of gene expression by bacterial proteins, stable transformants of AGS cells expressing gastrin or interleukin-8 (IL-8) promoters were cocultured with live organisms. Both whole-cell sonicates and a heat-stable fraction were also coincubated with the cells. A level of 108 organisms per ml stimulated both the gastrin and IL-8 promoters. Heat-stable proteins prepared from these bacterial sonicates stimulated the promoter significantly more than the live organism or unheated sonicates. A 38-kDa heat-stable protein stimulating the gastrin and IL-8 promoters was cloned and found to be an OmpA-related protein. Immunoblotting using antibody to the OmpA-like protein identified an Acinetobacter sp. as the bacterial species that expressed this protein and colonized the mouse stomach. Moreover, reintubation of mice with a pure culture of the Acinetobacter sp. caused gastritis. We conclude that bacterial colonization of the stomach may increase serum gastrin levels in part through the ability of the bacteria to produce OmpA-like proteins that directly stimulate gastrin and IL-8 gene expression. These results implicate OmpA-secreting bacteria in the activation of gastrin gene expression and raise the possibility that a variety of organisms may contribute to the increase in serum gastrin and subsequent epithelial cell proliferation in the hypochlorhydric stomach. PMID:10816525

  11. Dynamics of regulatory networks in gastrin-treated adenocarcinoma cells.

    PubMed

    Doni Jayavelu, Naresh; Bar, Nadav

    2014-01-01

    Understanding gene transcription regulatory networks is critical to deciphering the molecular mechanisms of different cellular states. Most studies focus on static transcriptional networks. In the current study, we used the gastrin-regulated system as a model to understand the dynamics of transcriptional networks composed of transcription factors (TFs) and target genes (TGs). The hormone gastrin activates and stimulates signaling pathways leading to various cellular states through transcriptional programs. Dysregulation of gastrin can result in cancerous tumors, for example. However, the regulatory networks involving gastrin are highly complex, and the roles of most of the components of these networks are unknown. We used time series microarray data of AR42J adenocarcinoma cells treated with gastrin combined with static TF-TG relationships integrated from different sources, and we reconstructed the dynamic activities of TFs using network component analysis (NCA). Based on the peak expression of TGs and activity of TFs, we created active sub-networks at four time ranges after gastrin treatment, namely immediate-early (IE), mid-early (ME), mid-late (ML) and very late (VL). Network analysis revealed that the active sub-networks were topologically different at the early and late time ranges. Gene ontology analysis unveiled that each active sub-network was highly enriched in a particular biological process. Interestingly, network motif patterns were also distinct between the sub-networks. This analysis can be applied to other time series microarray datasets, focusing on smaller sub-networks that are activated in a cascade, allowing better overview of the mechanisms involved at each time range.

  12. A high-fat diet regulates gastrin and acid secretion through primary cilia.

    PubMed

    Saqui-Salces, Milena; Dowdle, William E; Reiter, Jeremy F; Merchant, Juanita L

    2012-08-01

    The role of primary cilia in the gastrointestinal tract has not been examined. Here we report the presence of primary cilia on gastric endocrine cells producing gastrin, ghrelin, and somatostatin (Sst), hormones regulated by food intake. During eating, cilia in the gastric antrum decreased, whereas gastric acid and circulating gastrin increased. Mice fed high-fat chow showed a delayed decrease in antral cilia, increased plasma gastrin, and gastric acidity. Mice fed high-fat chow for 3 wk showed lower cilia numbers and acid but higher gastrin levels than mice fed a standard diet, suggesting that fat affects gastric physiology. Ex vivo experiments showed that cilia in the corpus responded to acid and distension, whereas cilia in the antrum responded to food. To analyze the role of gastric cilia, we conditionally deleted the intraflagellar transport protein Ift88 (Ift88(-/fl)). In fed Ift88(-/fl) mice, gastrin levels were higher, and gastric acidity was lower. Moreover, gastrin and Sst gene expression did not change in response to food as in controls. At 8 mo, Ift88(-/fl) mice developed foveolar hyperplasia, hypergastrinemia, and hypochlorhydria associated with endocrine dysfunction. Our results show that components of food (fat) are sensed by antral cilia on endocrine cells, which modulates gastrin secretion and gastric acidity.

  13. Cholecystokinin and gastrin receptors targeting in gastrointestinal cancer.

    PubMed

    Rai, Rajani; Chandra, Vishal; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2012-12-01

    Cholecystokinin and Gastrin are amongst the first gastrointestinal hormone discovered. In addition to classical actions (contraction of gallbladder, growth and secretion in the stomach and pancreas), these also act as growth stimulants for gastrointestinal malignancies and cell lines. Growth of these tumours is inhibited by antagonists of the cholecystokinin and gastrin receptors. These receptors provides most promising approach in clinical oncology and several specific radiolabelled ligands have been synthesized for specific tumour targeting and therapy of tumours overexpressing these receptors. Therefore, definition of the molecular structure of the receptor involved in the autocrine/paracrine loop may contribute to novel therapies for gastrointestinal cancer. Hence, this review tries to focus on the role and distribution of these hormones and their receptors in gastrointestinal cancer with a brief talk about the clinical trial using available agonist and antagonist in gastrointestinal cancers.

  14. Immunohistochemical examination of gastrin, gastrin precursors, and gastrin/CCK-2 receptor in human esophageal squamous cell carcinomas.

    PubMed

    Yuan, Aping; Liu, Jinzhong; Liu, Yiqing; Bjørnsen, Tone; Varro, Andrea; Cui, Guanglin

    2008-12-01

    A promoting effect of gastrin on stimulating Barrett's oesophagus proliferation has been demonstrated, but whether it plays a regulating role for esophageal squamous cell carcinoma (ESCC) to date has not been fully investigated. The aim of this study is to examine the expressions of gastrin, gastrin precursors and gastrin/CCK-2 receptor in ESCC. Tissue specimen sections from 38 patients with ESSC obtained from a high incidence area of north China were assessed using immunohistochemistry for amidated gastrin, gastrin precursors (progastrin and glycine-extended gastrin) and gastrin/CCK-2 receptors. Their clinical histopathological significance was also analyzed. Of 38 ESCC, the immunoreactivities of gastrin, glycine-extended gastrin and progastrin were observed in 13.2% (5/38), 7.9% (3/38) and 23.68% (9/38) cases. The expression of progastrin was obviously higher than other gastrins, though not significantly (P > 0.05). In positive cases for gastrin or glycine-extended gastrin, the scores of positive tumor cell numbers were at a lower density (<10/abundant-distributed field). However, the scores of progastrin positive tumor cell density in five of nine positive cases were over 10/abundant-distributed field. The immunoreactivity of gastrin/CCK-2 receptor was also observed in 15.8% (6/38) ESCC cases. There was not significant correlation regarding immunohistochemical results with known histomorphological parameters i.e. gender, tumor location and TNM stages. Based on our current results, ESCC tumor cells could be a possible cellular source of gastrin precursors, which has been postulated to play a role in regulating the growth in some human tumor cells.

  15. Gastrin: an acid-releasing, proliferative and immunomodulatory peptide?

    PubMed

    Calatayud, Sara; Alvarez, Angeles; Víctor, Víctor M

    2010-01-01

    Gastrin release is affected by gastric inflammatory conditions. Antral G cells respond to inflammatory mediators by increasing gastrin secretion. Accumulating experimental evidence suggests that gastrin exerts immunomodulatory and proinflammatory effects. Gastrin could be a contributing factor to these pathologies, which may constitute a new justification for pharmacological blockade of gastrin action.

  16. Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs.

    PubMed

    Grossini, Elena; Caimmi, Philippe; Molinari, Claudio; Uberti, Francesca; Mary, David; Vacca, Giovanni

    2011-01-01

    The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P <0.05). The potentiation of the cardiac response was observed only with the co-administration of pentagastrin and gastrin 17 (P <0.05). Moreover, blockade of muscarinic cholinoceptors (intravenous atropine) and of α-adrenoceptors (intravenous phentolamine) did not abolish the hemodynamic responses to gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of β-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nω-nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, β-adrenoceptors, and NO release.

  17. A duodenal role in gastrin release

    PubMed Central

    Hayes, J. R.; Ardill, Joy; Kennedy, T. L.; Buchanan, K. D.

    1974-01-01

    Observations on the plasma gastrin response to feeding protein in patients with the dumping syndrome, patients with pyloric stenosis, and patients asymptomatic after gastric surgery suggested that the duodenum might be important in the mechanism of gastrin release. This duodenal role was confirmed by the finding that when the stimulus was placed directly in the duodenum peak gastrin levels occurred earlier than when the stimulus was placed directly in the stomach. PMID:4422726

  18. Role of Annexin-II in GI cancers: interaction with gastrins/progastrins.

    PubMed

    Singh, Pomila

    2007-07-08

    The role of the gastrin peptide hormones (G17, G34) and their precursors (progastrins, PG; gly-extended gastrin, G-gly), in gastrointestinal (GI) cancers has been extensively reviewed in recent years [W. Rengifo-Cam, P. Singh, Role of progastrins and gastrins and their receptors in GI and pancreatic cancers: targets for treatment, Curr. Pharm. Des. 10 (19) (2004) 2345-2358; M. Dufresne, C. Seva, D. Fourmy, Cholecystokinin and gastrin receptors, Physiol. Rev. 86 (3) (2006) 805-847; A. Ferrand, T.C. Wang, Gastrin and cancer: a review, Cancer Lett. 238 (1) (2006) 15-29]. A possible important role of progastrin peptides in colon carcinogenesis has become evident from experiments with transgenic mouse models [W. Rengifo-Cam, P. Singh, (2004); A. Ferrand, T.C. Wang, (2006)]. It is now known that growth stimulatory and co-carcinogenic effects of gastrin/PG peptides are mediated by both proliferative and anti-apoptotic effects of the peptides on target cells [H. Wu, G.N. Rao, B. Dai, P. Singh, Autocrine gastrins in colon cancer cells Up-regulate cytochrome c oxidase Vb and down-regulate efflux of cytochrome c and activation of caspase-3, J. Biol. Chem. 275 (42) (2000) 32491-32498; H. Wu, A. Owlia, P. Singh, Precursor peptide progastrin(1-80) reduces apoptosis of intestinal epithelial cells and upregulates cytochrome c oxidase Vb levels and synthesis of ATP, Am. J. Physiol. Gastrointest. Liver Physiol. 285 (6) (2003) G1097-G1110]. Several receptor subtypes have been described that mediate growth effects of gastrin peptides [W. Rengifo-Cam, P. Singh (2004); M. Dufresne, C. Seva, D. Fourmy, (2006)]. Recently, we identified Annexin II as a high affinity binding protein for gastrin/PG peptides [P. Singh, H. Wu, C. Clark, A. Owlia, Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells, Oncogene (2006), doi:10.1038/sj.onc.1209798]. Importantly, the expression of

  19. The role of proteasome beta subunits in gastrin-mediated transcription of plasminogen activator inhibitor-2 and regenerating protein1.

    PubMed

    O'Hara, Adrian; Howarth, Alice; Varro, Andrea; Dimaline, Rod

    2013-01-01

    The hormone gastrin physiologically regulates gastric acid secretion and also contributes to maintaining gastric epithelial architecture by regulating expression of genes such as plasminogen activator inhibitor 2 (PAI-2) and regenerating protein 1 (Reg1). Here we examine the role of proteasome subunit PSMB1 in the transcriptional regulation of PAI-2 and Reg1 by gastrin, and its subcellular distribution during gastrin stimulation. We used the gastric cancer cell line AGS, permanently transfected with the CCK2 receptor (AGS-GR) to study gastrin stimulated expression of PAI-2 and Reg1 reporter constructs when PSMB1 was knocked down by siRNA. Binding of PSMB1 to the PAI-2 and Reg1 promoters was assessed by chromatin immunoprecipitation (ChIP) assay. Subcellular distribution of PSMB1 was determined by immunocytochemistry and Western Blot. Gastrin robustly increased expression of PAI-2 and Reg1 in AGS-GR cells, but when PSMB1 was knocked down the responses were dramatically reduced. In ChIP assays, following immunoprecipitation of chromatin with a PSMB1 antibody there was a substantial enrichment of DNA from the gastrin responsive regions of the PAI-2 and Reg1 promoters compared with chromatin precipitated with control IgG. In AGS-GR cells stimulated with gastrin there was a significant increase in the ratio of nuclear:cytoplasmic PSMB1 over the same timescale as recruitment of PSMB1 to the PAI-2 and Reg1 promoters seen in ChIP assays. We conclude that PSMB1 is part of the transcriptional machinery required for gastrin stimulated expression of PAI-2 and Reg1, and that its change in subcellular distribution in response to gastrin is consistent with this role.

  20. Gastrin upregulates the prosurvival factor secretory clusterin in adenocarcinoma cells and in oxyntic mucosa of hypergastrinemic rats.

    PubMed

    Fjeldbo, Christina Sæten; Bakke, Ingunn; Erlandsen, Sten Even; Holmseth, Jannicke; Lægreid, Astrid; Sandvik, Arne K; Thommesen, Liv; Bruland, Torunn

    2012-01-01

    We show that the gastric hormone gastrin induces the expression of the prosurvival secretory clusterin (sCLU) in rat adenocarcinoma cells. Clusterin mRNA was still upregulated in the presence of the protein synthesis inhibitor cycloheximide, although at a lower level. This indicates that gastrin induces clusterin transcription independently of de novo protein synthesis but requires de novo protein synthesis of signal transduction pathway components to achieve maximal expression level. Luciferase reporter assay indicates that the AP-1 transcription factor complex is involved in gastrin-mediated activation of the clusterin promoter. Gastrin-induced clusterin expression and subsequent secretion is dependent on sustained treatment, because removal of gastrin after 1-2 h abolished the response. Neutralization of secreted clusterin by a specific antibody abolished the antiapoptotic effect of gastrin on serum starvation-induced apoptosis, suggesting that extracellular clusterin is involved in gastrin-mediated inhibition of apoptosis. The clusterin response to gastrin was validated in vivo in hypergastrinemic rats, showing increased clusterin expression in the oxyntic mucosa, as well as higher levels of clusterin in plasma. In normal rat oxyntic mucosa, clusterin protein was strongly expressed in chromogranin A-immunoreactive neuroendocrine cells, of which the main cell type was the histidine decarboxylase-immunoreactive enterochromaffin-like (ECL) cell. The association of clusterin with neuroendocrine differentiation was further confirmed in human gastric ECL carcinoids. Interestingly, in hypergastrinemic rats, clusterin-immunoreactive cells formed distinct groups of diverse cells at the base of many glands. Our results suggest that clusterin may contribute to gastrin's growth-promoting effect on the oxyntic mucosa.

  1. Salt-inducible kinase 1 (SIK1) is induced by gastrin and inhibits migration of gastric adenocarcinoma cells.

    PubMed

    Selvik, Linn-Karina M; Rao, Shalini; Steigedal, Tonje S; Haltbakk, Ildri; Misund, Kristine; Bruland, Torunn; Prestvik, Wenche S; Lægreid, Astrid; Thommesen, Liv

    2014-01-01

    Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase (AMPK) family of kinases, all of which play major roles in regulating metabolism and cell growth. Recent studies have shown that reduced levels of SIK1 are associated with poor outcome in cancers, and that this involves an invasive cellular phenotype with increased metastatic potential. However, the molecular mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide hormone gastrin regulates cellular processes involved in oncogenesis, including proliferation, apoptosis, migration and invasion. The aim of this study was to examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J, AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER). We demonstrate that gastrin-mediated signalling induces phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic expression of SIK1 increases gastrin-induced phosphorylation of histone deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE-, SRE-, AP1- and NF-κB-driven luciferase reporter plasmids. We also show that gastrin induces phosphorylation and nuclear export of HDACs. Next we find that siRNA mediated knockdown of SIK1 increases migration of the gastric adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is regulated by gastrin and influences gastrin elicited signalling in gastric adenocarcinoma cells. The results from the present study are relevant for the understanding of molecular mechanisms involved in gastric adenocarcinomas.

  2. Gastrin mediated down regulation of ghrelin and its pathophysiological role in atrophic gastritis.

    PubMed

    Rau, T T; Sonst, A; Rogler, A; Burnat, G; Neumann, H; Oeckl, K; Neuhuber, W; Dimmler, A; Faller, G; Brzozowski, T; Hartmann, A; Konturek, P C

    2013-12-01

    The gastric hormone ghrelin is known as an important factor for energy homeostasis, appetite regulation and control of body weight. So far, ghrelin has mainly been examined as a serological marker for gastrointestinal diseases, and only a few publications have highlighted its role in local effects like mucus secretion. Ghrelin can be regarded as a gastroprotective factor, but little is known about the distribution and activity of ghrelin cells in pathologically modified tissues. We aimed to examine the morphological changes in ghrelin expression under several inflammatory, metaplastic and carcinogenic conditions of the upper gastrointestinal tract. In particular, autoimmune gastritis showed interesting remodeling effects in terms of ghrelin expression within neuroendocrine cell hyperplasia by immunohistochemistry. Using confocal laser microscopy, the gastrin/cholecystokinin receptor (CCKB) could be detected on normal ghrelin cells as well as in autoimmune gastritis. Functionally, we found evidence for a physiological interaction between gastrin and ghrelin in a primary rodent cell culture model. Additionally, we gathered serological data from patients with different basic gastrin levels due to long-term autoimmune gastritis or short-term proton pump inhibitor treatment with slightly reactive plasma gastrin elevations. Total ghrelin plasma levels showed a significantly inverse correlation with gastrin under long-term conditions. Autoimmune gastritis as a relevant condition within gastric carcinogenesis therefore has two effects on ghrelin-positive cells due to hypergastrinemia. On the one hand, gastrin stimulates the proliferation of ghrelinpositive cells as integral part of neuroendocrine cell hyperplasia, while on the other hand, plasma ghrelin is reduced by gastrin and lost in pseudopyloric and intestinal metaplastic areas. Ghrelin is necessary for the maintenance of the mucosal barrier and might play a role in gastric carcinogenesis, if altered under these pre

  3. Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis.

    PubMed

    Chen, Yue; Asico, Laureano D; Zheng, Shuo; Villar, Van Anthony M; He, Duofen; Zhou, Lin; Zeng, Chunyu; Jose, Pedro A

    2013-11-01

    Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (cholecystokinin B receptor [CCKBR]; CI-988) or a D1-like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats. The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT cells from Wistar-Kyoto but not spontaneously hypertensive rats, stimulation of either D1-like receptor or gastrin receptor inhibited Na(+)-K(+)-ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from Wistar-Kyoto and spontaneously hypertensive rats, CCKBR and D1 receptor coimmunoprecipitated, which was increased after stimulation of either D1 receptor or CCKBR in RPT cells from Wistar-Kyoto rats; stimulation of one receptor increased the RPT cell membrane expression of the other receptor, effects that were not observed in spontaneously hypertensive rats. These data suggest that there is a synergism between CCKBR and D1-like receptors to increase sodium excretion. An aberrant interaction between the renal CCK BR and D1-like receptors (eg, D1 receptor) may play a role in the pathogenesis of hypertension.

  4. Prosequence switching: an effective strategy to produce biologically active E. coli heat-stable enterotoxin STh.

    PubMed

    Weiglmeier, Philipp R; Berkner, Hanna; Seebahn, Angela; Vogel, Nico; Schreiber, Rainer; Wöhrl, Birgitta M; Schwarzinger, Stephan; Rösch, Paul

    2014-01-01

    Enterotoxigenic Escherichia coli (ETEC) infections account for the majority of cases of acute secretory diarrhea. The causative agents are enterotoxins secreted by ETEC, among them is the heat-stable enterotoxin, STh. STh is a 19-amino acid peptide containing three disulfide bonds that stimulates fluid secretion in the bowel by binding to the receptor domain of intestinal guanylyl cyclase C (GC-C). Since GC-C agonists have pharmacologic potential for diagnosis and treatment of disorders such as constipation-predominant irritable bowel syndrome (IBS-C), chronic constipation, and colorectal carcinoma, it is crucial to develop methods for the large-scale production of STh and related peptides. Here, we present a strategy for recombinant expression of STh that relies on the use of the prosequence of human uroguanylin to support proper folding and disulfide bond formation. The chimeric protein CysCys-STh consisting of the propeptide of uroguanylin as N-terminus and the STh peptide as C-terminus was expressed in E. coli, and an efficient purification protocol was developed. Trypsin digestion of this protein released the enterotoxin which could be obtained in high purity. NMR and mass spectrometry confirmed the identity and homogeneity of the toxin, and its biological activity was confirmed by a cell-based in vivo assay. The expression scheme introduced here represents a cost-efficient and scalable way of STh production.

  5. Importance of gastrin in the pathogenesis and treatment of gastric tumors

    PubMed Central

    Burkitt, Michael D; Varro, Andrea; Pritchard, D Mark

    2009-01-01

    In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia, such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects. PMID:19115463

  6. Regulated expression of the human gastrin gene in mice.

    PubMed

    Mensah-Osman, Edith; Labut, Ed; Zavros, Yana; El-Zaatari, Mohamad; Law, David J; Merchant, Juanita L

    2008-11-29

    Gastrin is secreted from neuroendocrine cells residing in the adult antrum called G cells, but constitutively low levels are also expressed in the duodenum and fetal pancreas. Gastrin normally regulates gastric acid secretion by stimulating the proliferation of enterochromaffin-like cells and the release of histamine. Gastrin and progastrin forms are expressed in a number of pathological conditions and malignancies. However, the DNA regulatory elements in the human versus the mouse gastrin promoters differ suggesting differences in their transcriptional control. Thus, we describe here the expression of the human gastrin gene using a bacterial artificial chromosome (BAC) in the antral and duodenal cells of gastrin null mice. All 5 founder lines expressed the 253 kb human gastrin BAC. hGasBAC transgenic mice were bred onto a gastrin null background so that the levels of human gastrin peptide could be analyzed by immunohistochemistry and radioimmunoassay without detecting endogenous mouse gastrin. We have shown previously that chronically elevated gastrin levels suppress somatostatin. Indeed, infusion of amidated rat gastrin depressed somatostatin levels, stimulated gastric acid secretion and an increase in the numbers of G cells in the antrum and duodenum. In conclusion, human gastrin was expressed in mouse enteroendocrine cells and was regulated by somatostatin. This mouse model provides a unique opportunity to study regulation of the human gastrin promoter in vivo by somatostatin and possibly other extracellular regulators contributing to our understanding of the mechanisms involved in transcriptional control of the human gene.

  7. Radioimmunoassay of gastrin: studies in pernicious anaemia

    PubMed Central

    Hansky, J.; Korman, M. G.; Soveny, C.; John, D. J. B. St

    1971-01-01

    Serum gastrin levels in patients with pernicious anaemia were measured by immunoassay in the fasting state, following gastric perfusion with 0·9% saline, 0·1N hydrochloric acid, and solutions of increasing acidity, and after the intravenous injection or infusion of secretin. The fasting serum gastrin level was measured in 21 patients with pernicious anaemia and found to be elevated at 1,036 ± 215 pg per ml. Gastric perfusion with saline (pH 4·7) caused a mean fall in serum gastrin of 30% in four patients; perfusion with hydrochloric acid caused a further slight fall. Perfusion with solutions of increasing acidity resulted in a sharp fall in serum gastrin levels when the acidity was changed from pH 6 to pH 4. A single intravenous injection of secretin produced a mean maximal fall of 44% in the serum gastrin level in four patients, whereas continuous infusion of secretin produced a fall of 35% in four other patients. These studies suggest that the gastrin-secreting cells of the stomach are not affected by the atrophic process in pernicious anaemia and remain subject to the regulating control of acid and secretin. PMID:5548565

  8. Helicobacter pylori related hypergastrinaemia is the result of a selective increase in gastrin 17.

    PubMed Central

    Mulholland, G; Ardill, J E; Fillmore, D; Chittajallu, R S; Fullarton, G M; McColl, K E

    1993-01-01

    Helicobacter pylori infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylori. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that > 90% of the circulating gastrin consisted of gastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmol/l (8-39) (p < 0.05), entirely because of a fall in G17 from 6 pmol/l (< 2.4-25) to < 2.4 pmol/l (< 2.4-23) (p < 0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmol/l (38-114) to 33 pmol/l (19-88) (p < 0.005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmol/l (< 2.4-52) (p < 0.001). The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmol/l, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylori infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylori predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration of gastrin in H pylori infection is the result of an increase in one of the main biologically active forms of the hormone. PMID:8314507

  9. Ulex europaeus agglutinin-I binds to developing gastrin cells.

    PubMed

    Ge, Z H; Blom, J; Larsson, L I

    1998-03-01

    We have previously reported that antropyloric gastrin (G) and somatostatin (D) cells derive from precursor (G/D) cells that coexpress both hormones. We have now analyzed this endocrine cell pedigree for binding of Ulex europaeus agglutinin-I (UEA-I), which previously has been reported to represent a useful marker for cell differentiation. Subpopulations of G/D, D, and G cells were all found to express UEA-I binding. Labelling with bromodeoxyuridine showed that UEA-I positive G cells possessed a higher labelling index than UEA-I negative G cells. These data suggest that the UEA-I positive G cells represent maturing cells still involved in DNA synthesis and cell division. Electron microscopically, specific UEA-I binding sites were localized to the secretory granules and the apical cell membrane of G cells. We conclude that UEA-I represents a differentiation marker for G cells. Moreover, the presence of UEA-I binding sites in these cells may be relevant for Helicobacter pylori-mediated disturbances of gastric acid secretion and gastrin hypersecretion.

  10. A GC-rich element confers epidermal growth factor responsiveness to transcription from the gastrin promoter.

    PubMed Central

    Merchant, J L; Demediuk, B; Brand, S J

    1991-01-01

    Epidermal growth factor (EGF) and transforming growth factor alpha are important determinants of mucosal integrity in the gastrointestinal tract, and they act both directly and indirectly to prevent ulceration in the stomach. Consistent with this physiological role, EGF stimulates transcription of gastrin, a peptide hormone which regulates gastric acid secretion and mucosal growth. EGF stimulation of gastrin transcription is mediated by a GC-rich gastrin EGF response element (gERE) (GGGGCGGGGTGGGGGG) which lies between -54 and -68 in the human gastrin promoter. The gERE sequence also confers weaker responsiveness to phorbol ester stimulation. The gERE sequence differs from previously described EGF response elements. The gERE DNA sequence specifically interacts with a GH4 DNA-binding protein distinct from previously described transcription factors (Egr-1 and AP2) which bind GC-rich sequences and mediate transcriptional activation by growth factors. Furthermore, the gERE element does not bind the Sp1 transcription factor even though the gERE sequence contains a high-affinity Sp1-binding site (GGCGGG). Images PMID:2017173

  11. Stimulation of proliferation in the colorectal mucosa by gastrin precursors is blocked by desferrioxamine.

    PubMed

    Ferrand, Audrey; Lachal, Shamilah; Bramante, Gianni; Kovac, Suzana; Shulkes, Arthur; Baldwin, Graham S

    2010-07-01

    Precursors of the peptide hormone gastrin stimulate proliferation in the colorectal mucosa and promote the development of colorectal carcinoma. Gastrins bind two ferric ions selectively and with high affinity, and the biological activity of glycine-extended gastrin (Ggly) in vitro is dependent on the presence of ferric ions. The aim of the present study was to determine whether or not iron is required for biological activity of progastrin and Ggly in vivo. Rats that had undergone a colostomy were infused with Ggly, and proliferation was measured in the defunctioned rectal mucosa. Proliferation was also measured in the colonic mucosa of hGAS and MTI-Ggly mice, which, by definition, overexpress progastrin and Ggly, respectively. The requirement for iron was assessed by thrice-weekly injection of the chelating agent desferrioxamine (DFO). The proliferation index in the defunctioned rectal mucosa was significantly increased in the Ggly-infused rats, and the increase was significantly reduced after treatment with DFO. Treatment with DFO significantly reduced the crypt height and proliferation index in the colonic mucosa of hGAS and MTI-Ggly mice but had no effect on the same variables in wild-type mice. These observations are consistent with the hypothesis that the biological activity of progastrin and Ggly in vivo is dependent on the presence of ferric ions and further suggest that chelating agents may block the stimulatory effects of gastrin precursors in the development of colorectal carcinoma.

  12. Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators.

    PubMed

    Seim-Wikse, T; Kolbjørnsen, O; Jörundsson, E; Benestad, S L; Bjornvad, C R; Grotmol, T; Kristensen, A T; Skancke, E

    2014-01-01

    Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator for gastric carcinoma in man. Gastric carcinoma is rare in dogs and generally carries a grave prognosis. In this study, the expression of gastrin was investigated immunohistochemically in gastric biopsy samples from 64 dogs with gastric carcinoma. Serum gastrin concentrations were measured in 15 of these dogs and compared with those of seven healthy control dogs. Tumour tissue expressed gastrin in 8% (5/64) of the dogs with gastric carcinoma. There was no significant difference in serum gastrin concentrations between dogs with gastric carcinoma and healthy controls (P = 0.08). Expression of gastrin in gastric carcinomas is less common in dogs than in man and may therefore not be relied on as a prognostic marker in this species. Serum gastrin concentration alone is also not a useful biomarker for gastric carcinoma in dogs.

  13. Gastrin Receptor-Avid Peptide Conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2005-07-26

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  14. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, C. A.

    2001-01-01

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  15. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2006-12-12

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  16. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Sieckman, Gary; Smith, Charles J.; Gali, Hariprasad

    2006-06-13

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a-moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  17. Gastrin receptors on isolated canine parietal cells

    SciTech Connect

    Soll, A.H.; Amirian, D.A.; Thomas, L.P.; Reedy, T.J.; Elashoff, J.D.

    1984-05-01

    The receptors in the fundic mucosa that mediate gastrin stimulation of acid secretion have been studied. Synthetic human gastrin-17-I (G17) with a leucine substitution in the 15th position ((Leu15)-G17) was iodinated by chloramine T; high saturable binding was found to enzyme-dispersed canine fundic mucosal cells. /sup 127/I-(Leu15)-G17, but not /sup 127/I-G17, retained binding potency and biological activity comparable with uniodinated G17. Fundic mucosal cells were separated by size by using an elutriator rotor, and specific /sup 125/I-(Leu-15)-G17 binding in the larger cell fractions was highly correlated with the distribution of parietal cells. There was, however, specific gastrin binding in the small cell fractions, not accounted for by parietal cells. Using sequential elutriation and stepwise density gradients, highly enriched parietal and chief cell fractions were prepared; /sup 125/I-(Leu15)-G17 binding correlated positively with the parietal cell (r . 0.98) and negatively with chief cell content (r . -0.96). In fractions enriched to 45-65% parietal cells, specific /sup 125/I-(Leu15)-G17 binding was rapid, reaching a steady state at 37 degrees C within 30 min. Dissociation was also rapid, with the rate similar after 100-fold dilution or dilution plus excess pentagastrin. At a tracer concentration from 10 to 30 pM, saturable binding was 7.8 +/- 0.8% per 10(6) cells (mean +/- SE) and binding in the presence of excess pentagastrin accounted for 11% of total binding. G17 and carboxyl terminal octapeptide of cholecystokinin (26-33) were equipotent in displacing tracer binding and in stimulating parietal cell function ((/sup 14/C)aminopyrine accumulation), whereas the tetrapeptide of gastrin (14-17) had a much lower potency. Proglumide inhibited gastrin binding and selectively inhibited gastrin stimulation of parietal cell function.

  18. Bismuth ions inhibit the biological activity of non-amidated gastrins in vivo.

    PubMed

    Kovac, Suzana; Loh, Su-Wen; Lachal, Shamilah; Shulkes, Arthur; Baldwin, Graham S

    2012-02-15

    The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. Bi3+ ions also bind to glycine-extended gastrin17 (Ggly), but inhibit Ggly-induced cell proliferation and migration in gastrointestinal cell lines in vitro. The aims of the present study were firstly, to establish the mechanism by which Bi3+ ions inhibit the binding of Fe3+ ions to Ggly, and secondly, to test the effect of Bi3+ ions on the activity of non-amidated gastrins in vivo. The interaction between Bi3+ ions, Fe3+ ions and Ggly was investigated by ultraviolet spectroscopy. The effect of Bi3+ ions on colorectal mucosal proliferation was measured in three animal models. In vitro in the presence of Bi3+ ions the affinity of Fe3+ ions for Ggly was substantially reduced; the data was better fitted by a mixed, rather than a competitive, inhibition model. In rats treated with Ggly alone proliferation in the rectal mucosa was increased by 318%, but was reduced to control values (p < 0.001) in animals receiving oral bismuth plus Ggly. Proliferation in the colonic mucosa of mice overexpressing Ggly or progastrin was significantly greater than in wild-type mice, but was no greater than control (p < 0.01) in animals receiving oral bismuth. Thus a reduction in the binding of Fe3+ ions to Ggly and progastrin in the presence of Bi3+ ions is a likely explanation for the ability of oral bismuth to block the biological activity of non-amidated gastrins in vivo.

  19. Involvement of STH7 in light-adapted development in Arabidopsis thaliana promoted by both strigolactone and karrikin.

    PubMed

    Thussagunpanit, Jutiporn; Nagai, Yuko; Nagae, Miyu; Mashiguchi, Kiyoshi; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Nakano, Takeshi; Nakamura, Hidemitsu; Asami, Tadao

    2017-02-01

    Strigolactones (SLs) and karrikins (KARs) regulate photomorphogenesis. GR24, a synthetic SL and KAR1, a KAR, inhibit the hypocotyl elongation of Arabidopsis thaliana in a weak light. GR24 and KAR1 up-regulate the expression of STH7, encoding a transcription factor belonging to the double B-box zinc finger subfamily. In this study, we used STH7-overexpressing (STH7ox) lines and functionally defective STH7 (STH7-SRDX) mutants to investigate roles of SLs and KARs in photomorphogenesis of Arabidopsis. Hypocotyl elongation of STH7-SRDX mutants was less sensitive to both GR24 and KAR1 treatment than that of wild-type Arabidopsis under weak light conditions. Furthermore, the chlorophyll and anthocyanin content was increased in STH7ox lines when de-etiolated with light and GR24-treated plants had enhanced anthocyanin production. GR24 and KAR1 treatment significantly increased the expression level of photosynthesis-related genes LHCB1 and rbcS. The results strongly suggest that SL and KAR induce photomorphogenesis of Arabidopsis in an STH7-dependent manner.

  20. The Effects of Secretin, Pancreozymin, and Gastrin on Insulin and Glucagon Secretion in Anesthetized Dogs *

    PubMed Central

    Unger, Roger H.; Ketterer, Hermann; Dupré, John; Eisentraut, Anna M.

    1967-01-01

    The effects upon islet hormone secretion of highly purified preparations of secretin and of pancreozymin-cholecystokinin and of a crude gastrin-containing extract of hog antrum have been studied in acutely operated dogs. All three preparations were shown to cause a striking increase in insulin concentration in the pancreaticoduodenal venous plasma after their rapid endoportal injection in anesthetized dogs. With each hormone preparation, the peak in insulin secretion occurred 1 minute after injection, and a rapid decline was observed immediately thereafter. Whereas secretin and gastrin failed to alter significantly the pancreaticoduodenal venous glucagon or arterial glucose concentration, pancreozymin caused a dramatic rise in pancreaticoduodenal venous glucagon concentration, which reached a peak 3 minutes after injection, and hyperglycemia was noted to occur soon thereafter. Endoportal infusion of secretin and pancreozymin for 20 minutes caused responses that were sustained but qualitatively identical to the responses noted after rapid injection of the hormones. The beta-cytotropic effect of secretin was abolished by the infusion of epinephrine. These results could not be attributed to the small degree of contamination of the enteric hormone preparations with insulin or glucagon, and it would appear that secretin, pancreozymin, and probably gastrin have insulin-releasing activity and that pancreozymin has, in addition, glucagon-releasing activity. The demonstration that these three hormones possess insulin-releasing activity suggests that there is in the gastrointestinal tract a chain of betacytotropic hormones from antrum to ileum that is capable of augmenting insulin secretion as required for disposal of substrate loads. It is suggested that the existence of this “entero-insular axis” prevents high substrate concentrations that would otherwise follow ingestion of large meals were the insular response entirely a function of arterial substrate concentration

  1. Hormones

    MedlinePlus

    ... affect many different processes, including Growth and development Metabolism - how your body gets energy from the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the ...

  2. [The role of hormones from the mucosa of the gastric antrum in regulating gastric secretion].

    PubMed

    Groĭsman, S D; Gubkin, V A; Babenkov, G D

    1993-09-01

    Removal of antral mucosa obviously reduced the sensitivity of glandulocytes to pentagastrin in dogs with Basov-Pavlov fistulae. Activation of the endocrinal cells of the antral mucosa after fundal and antral parts separation exerted an opposite effect. The data obtained suggest that, along with gastrin, there is another hormonal factor facilitating the action of gastrin in the antral mucosa.

  3. Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases

    PubMed Central

    Berna, Marc J.; Jensen, Robert T.

    2009-01-01

    In this paper, the estabished and possible roles of CCK1 and CCK2 receptors in gastrointestinal (GI) and metabolic diseases are reviewed and available results from human agonist/antagonist studies are discussed. While there is evidence for the involvement of CCK1R in numerous diseases including pancreatic disorders, motility disorders, tumor growth, regulation of satiety and a number of CCK-deficient states, the role of CCK1R in these conditions is not clearly defined. There are encouraging data from several clinical studies of CCK1R antagonists in some of these conditions, but their role as therapeutic agents remains unclear. The role of CCK2R in physiological (atrophic gastritis, pernicious anemia) and pathological (Zollinger-Ellison syndrome) hypergastrinemic states, its effects on the gastric mucosa (ECL cell hyperplasia, carcinoids, parietal cell mass) and its role in acid-peptic disorders are clearly defined. Furthermore, recent studies point to a possible role for CCK2R in a number of GI malignancies. Current data from human studies of CCK2R antagonists are presented and their potential role in the treatment of these conditions reviewed. Furthermore, the role of CCK2 receptors as targets for medical imaging is discussed. Even though cholecystokinin (CCK) and gastrin were among the first gastrointestinal hormones discovered [1,2], both their physiological roles as well as their roles in clinically relevant gastrointestinal diseases remain unclear and even controversial in many cases [3–6]. The structural characterization of CCK and gastrin [7,8], pharmacological identification [9–13] and cloning [14,15] of CCK and gastrin receptors (CCK1R, CCK2R), characterization of receptor location, peptide and receptor genes, development of receptor antagonists and receptor/agonist knockout animals [16–21] have led to important advancements in our understanding of the physiological and pathophysiological role of CCK and gastrin signaling [3]. Most of these topics

  4. Analytical expression of s-th power of Gram matrix for group covariant signals and its application

    NASA Astrophysics Data System (ADS)

    Usuda, T. S.; Shiromoto, K.

    2011-10-01

    Analytical expression of s-th power of the Gram matrix is shown when the quantum signals are group covariant. An application of the formula to coded quantum signals by classical linear codes over a finite field is also shown.

  5. CI-988 Inhibits EGFR Transactivation and Proliferation Caused by Addition of CCK/Gastrin to Lung Cancer Cells.

    PubMed

    Moody, Terry W; Nuche-Berenguer, Bernardo; Moreno, Paola; Jensen, Robert T

    2015-07-01

    Cholecystokinin (CCK) receptors are G-protein coupled receptors (GPCR) which are present on lung cancer cells. CCK-8 stimulates the proliferation of lung cancer cells, whereas the CCK2R receptor antagonist CI-988 inhibits proliferation. GPCR for some gastrointestinal hormones/neurotransmitters mediate lung cancer growth by causing epidermal growth factor receptor (EGFR) transactivation. Here, the role of CCK/gastrin and CI-988 on EGFR transactivation and lung cancer proliferation was investigated. Addition of CCK-8 or gastrin-17 (100 nM) to NCI-H727 human lung cancer cells increased EGFR Tyr(1068) phosphorylation after 2 min. The ability of CCK-8 to cause EGFR tyrosine phosphorylation was blocked by CI-988, gefitinib (EGFR tyrosine kinase inhibitor), PP2 (Src inhibitor), GM6001 (matrix metalloprotease inhibitor), and tiron (superoxide scavenger). CCK-8 nonsulfated and gastrin-17 caused EGFR transactivation and bound with high affinity to NCI-H727 cells, suggesting that the CCK2R is present. CI-988 inhibited the ability of CCK-8 to cause ERK phosphorylation and elevate cytosolic Ca(2+). CI-988 or gefitinib inhibited the basal growth of NCI-H727 cells or that stimulated by CCK-8. The results indicate that CCK/gastrin may increase lung cancer proliferation in an EGFR-dependent manner.

  6. Sex-related Differences in Gastrin Release and Parietal Cell Sensitivity to Gastrin in Healthy Human Beings

    PubMed Central

    Feldman, M.; Richardson, C. T.; Walsh, J. H.

    1983-01-01

    We compared serum gastrin concentrations and gastric acid secretion basally and in response to a mixed meal in age-matched women and men. Women had significantly higher basal serum gastrin concentrations (P < 0.01) and two- to threefold higher food-stimulated serum gastrin concentrations (P < 0.001) than men. Basal and food-stimulated serum gastrin concentrations in women did not fluctuate significantly during the menstrual cycle. Sex-related differences in food-stimulated serum gastrin concentrations were not due to differences in antral pH because pH after the meal in women and men had been kept constant at 5.0 by in vivo intragastric titration with sodium bicarbonate. Studies using an antibody that reacts only with potent gastrin heptadecapeptide species (G-17-I and II) indicated that women also had threefold higher serum G-17 concentrations after the meal than men (P < 0.005). Elevated serum G-17 concentrations after the meal in women were due to increased release of G-17 rather than slower clearance of G-17 from the circulation. Despite elevated serum gastrin concentrations in response to food, women secreted approximately the same amount of acid relative to their maximal secretory capacity as men. Furthermore, during exogenous G-17 infusion, which led to identical serum gastrin concentrations in women and men, the dose-response curve for acid secretion in women was shifted significantly to the right of the G-17 dose-response curve in men (P < 0.02). The dose of G-17 that stimulated half of peak acid secretion was two to three times higher in women than in men, reflecting significantly reduced sensitivity of parietal cells to gastrin in women (P < 0.05). Our studies suggest that, compared with men, women release greater amounts of gastrin but are at the same time less sensitive to stimulation of acid secretion by gastrin. PMID:6826731

  7. Expression of cholecystokinin2-receptor in rat and human L cells and the stimulation of glucagon-like peptide-1 secretion by gastrin treatment.

    PubMed

    Cao, Yang; Cao, Xun; Liu, Xiao-Min

    2015-03-01

    Gastrin is a gastrointestinal hormone secreted by G cells. Hypergastrinemia can improve blood glucose and glycosylated hemoglobin levels. These positive effects are primarily due to the trophic effects of gastrin on β-cells. In recent years, many receptors that regulate secretion of glucagon-like peptide 1 (GLP-1) have been identified in enteroendocrine L cell lines. This led us to hypothesize that, in addition to the trophic effects of gastrin on β-cells, L cells also express cholecystokinin2-receptor (CCK2R), which may regulate GLP-1 secretion and have synergistic effects on glucose homeostasis. Our research provides a preliminary analysis of CCK2R expression and the stimulating effect of gastrin treatment on GLP-1 secretion in a human endocrine L cell line, using RT-PCR, Western blot, immunocytochemistry, and ELISA analyses. The expression of proglucagon and prohormone convertase 3, which regulate GLP-1 biosynthesis, were also analyzed by real-time PCR. Double immunofluorescence labeling was utilized to assess the intracellular localization of CCK2R and GLP-1 in L cells harvested from rat colon tissue. Our results showed that CCK2R was expressed in both the human L cell line and the rat L cells. We also showed that treatment with gastrin, a CCK2R agonist, stimulated the secretion of GLP-1, and that this effect was likely due to increased expression of proglucagon and PCSK1 (also known as prohormone convertase 3 (PC3 gene)). These results not only provide a basis for the role gastrin may play in intestinal L cells, and may also provide the basis for the development of a method of gastrin-mediated glycemic regulation.

  8. Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17.

    PubMed

    Rehfeld, Jens F; Zhu, Xiaorong; Norrbom, Christina; Bundgaard, Jens R; Johnsen, Anders H; Nielsen, John E; Vikesaa, Jonas; Stein, Jeffrey; Dey, Arunangsu; Steiner, Donald F; Friis-Hansen, Lennart

    2008-10-01

    Cellular synthesis of peptide hormones requires PCs (prohormone convertases) for the endoproteolysis of prohormones. Antral G-cells synthesize the most gastrin and express PC1/3, 2 and 5/6 in the rat and human. But the cleavage sites in progastrin for each PC have not been determined. Therefore, in the present study, we measured the concentrations of progastrin, processing intermediates and alpha-amidated gastrins in antral extracts from PC1/3-null mice and compared the results with those in mice lacking PC2 and wild-type controls. The expression of PCs was examined by immunocytochemistry and in situ hybridization of mouse G-cells. Finally, the in vitro effect of recombinant PC5/6 on progastrin and progastrin fragments containing the relevant dibasic cleavage sites was also examined. The results showed that mouse G-cells express PC1/3, 2 and 5/6. The concentration of progastrin in PC1/3-null mice was elevated 3-fold. Chromatography showed that cleavage of the Arg(36)Arg(37) and Arg(73)Arg(74) sites were grossly decreased. Accordingly, the concentrations of progastrin products were markedly reduced, alpha-amidated gastrins (-34 and -17) being 25% of normal. Lack of PC1/3 was without effect on the third dibasic site (Lys(53)Lys(54)), which is the only processing site for PC2. Recombinant PC5/6 did not cleave any of the dibasic processing sites in progastrin and fragments containing the relevant dibasic processing sites. The complementary cleavages of PC1/3 and 2, however, suffice to explain most of the normal endoproteolysis of progastrin. Moreover, the results show that PCs react differently to the same dibasic sequences, suggesting that additional structural factors modulate the substrate specificity.

  9. The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging.

    PubMed

    Sturzu, Alexander; Klose, Uwe; Sheikh, Sumbla; Echner, Hartmut; Kalbacher, Hubert; Deeg, Martin; Nägele, Thomas; Schwentner, Christian; Ernemann, Ulrike; Heckl, Stefan

    2014-02-14

    The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications.

  10. Autoantibody to the gastrin receptor in pernicious anemia

    SciTech Connect

    de Aizpurua, H.J.; Ungar, B.; Toh, B.H.

    1985-08-22

    The authors examined serum IgG fractions from 20 patients with pernicious anemia and 25 control subjects for their capacity to inhibit binding of (/sup 125/I)15-leu human gastrin-17 to parietal-cell-enriched gastric mucosal cells. IgG fractions from six patients reduced gastrin binding by 45.6 +/- 12.2 per cent, as compared with a reduction of 1.8 +/- 0.7 per cent by fractions from the 25 controls. The fractions from these six patients also reduced gastrin-stimulated (/sup 14/C)aminopyrine uptake by gastric cells (an index of gastric acid secretory activity in vitro) by 50.2 +/- 8.4 per cent (mean +/- S.D.), as compared with 9.2 +/- 4.1 per cent for the controls. IgG fractions from six other patients that did not reduce gastrin binding also inhibited gastrin-stimulated (/sup 14/C)aminopyrine uptake, by 48.1 +/- 9.1 per cent. These reductions in gastrin binding and aminopyrine uptake were abolished by absorption of the IgG fractions with suspensions of viable gastric mucosal cells but not by absorption with liver or kidney cells. The IgG fractions did not inhibit (/sup 3/H)histamine binding or histamine-stimulated (/sup 14/C)aminopyrine uptake. These results suggest that serum IgG from some patients with pernicious anemia contains autoantibodies to the gastrin receptor.

  11. Quantifying the Local Seebeck Coefficient using Scanning Thermoelectric Microscopy (SThEM)

    NASA Astrophysics Data System (ADS)

    Walrath, Jenna; Lin, Yen-Hsiang; Pipe, Kevin; Goldman, Rachel

    2013-03-01

    Thermoelectric (TE) devices allow reliable solid-state conversion of heat to electricity. The efficiency of a TE device is determined by the figure of merit, ZT, which is sensitive to the Seebeck coefficient, S. A promising alternative to traditional macroscale measurements of S is scanning thermoelectric microscopy (SThEM), which can profile S with nm resolution. In SThEM, an unheated scanning tunneling microscopy tip acts as a high-resolution voltmeter probe to measure the thermally-induced voltage, V, in a heated sample. However, the temperature (T) gradient is not localized to the sample, and the measured V is a convolution of voltages within the region of non-zero temperature gradient. Therefore we have developed a 1D Fourier heat conduction model to predict the T gradient in the tip and to deconvolute the measured V within the sample. This approach enables direct conversion between the measured V and the local S. This material is based upon work supported by the Department of Energy under Award Number DE-PI0000012. Y.H. Lin and R.S. Goldman are supported in part by the DOE under contract No. DE-FG02-06ER46339.

  12. GASTRIN-RELEASING PEPTIDE RECEPTOR IN BREAST CANCER MEDIATES CELLULAR MIGRATION AND INTERLEUKIN-8 EXPRESSION

    PubMed Central

    Chao, Celia; Ives, Kirk; Hellmich, Helen L.; Townsend, Courtney M.; Hellmich, Mark R.

    2015-01-01

    Background Breast cancers aberrantly express gastrin-releasing peptide (GRP) hormone and its cognate receptor, gastrin-releasing peptide receptor (GRP-R). Experimental evidence suggests that bombesin (BBS), the pharmacological homologue of GRP, promotes breast cancer growth and progression. The contribution of GRP-R to other poor prognostic indicators in breast cancer, such as the expression of the EGF-R family of growth factors, and hormone insensitivity is unknown. Materials and Methods Two estrogen receptor (ER)-negative breast cancer cell lines were used. MDA-MB-231 overexpress both EGFR and GRPR, whereas SK-BR-3 cells express EGF-R but lack GRP-R. Cellular proliferation was assessed by Coulter counter. Chemotactic migration was performed using Transwell chambers and the migrated cells were quantified. Northern blot and real-time PCR were used to evaluate if pro-angiogenic factor interleukin-8 (IL-8) mRNA expression. Results In MDA-MB-231 cells, GRP-R and EGF-R synergize to regulate cell migration, IL-8 expression, but not cell proliferation. In SK-BR-3 cells, ectopic expression of GRP-R was sufficient to increase migration and IL-8 mRNA. Conclusions These data suggest relevant roles for GRP-R in ER-negative breast cancer progression. Future mechanistic studies to define the molecular role of GRP-R in breast cancer metastasis provide novel targets for the treatment of ER-negative breast cancers. PMID:19631337

  13. Serum gastrin in canine chronic lymphocytic-plasmacytic enteritis

    PubMed Central

    2005-01-01

    Abstract This study evaluates serum gastrin concentrations in dogs with chronic lymphocytic-plasmacytic enteritis, as well as its possible relationship with the severity of lesions present in the stomach. To achieve this aim, 5 dogs without gastrointestinal disease and 15 dogs with chronic lymphocytic-plasmacytic enteritis were included. Serum gastrin concentrations were significantly increased in dogs with chronic lymphocytic-plasmacytic enteritis compared with those in dogs without gastrointestinal disease. Also, there was a positive correlation between the severity of the gastric lesion and the serum gastrin concentration. Our findings indicate the possibility that gastrin plays a role in the etiology of an accompanying chronic antral gastritis in canine chronic lymphocytic-plasmacytic enteritis. PMID:16152719

  14. Gastrin attenuates ischemia-reperfusion-induced intestinal injury in rats

    PubMed Central

    Liu, Zhihao; Luo, Yongli; Cheng, Yunjiu; Zou, Dezhi; Zeng, Aihong; Yang, Chunhua

    2016-01-01

    Intestinal ischemia-reperfusion (I/R) injury is a devastating complication when the blood supply is reflowed in ischemic organs. Gastrin has critical function in regulating acid secretion, proliferation, and differentiation in the gastric mucosa. We aimed to determine whether gastrin has an effect on intestinal I/R damage. Intestinal I/R injury was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion, and the rats were induced to be hypergastrinemic by pretreated with omeprazole or directly injected with gastrin. Some hypergastrinemic rats were injected with cholecystokinin-2 (CCK-2) receptor antagonist prior to I/R operation. After the animal surgery, the intestine was collected for histological analysis. Isolated intestinal epithelial cells or crypts were harvested for RNA and protein analysis. CCK-2 receptor expression, intestinal mucosal damage, cell apoptosis, and apoptotic protein caspase-3 activity were measured. We found that high gastrin in serum significantly reduced intestinal hemorrhage, alleviated extensive epithelial disruption, decreased disintegration of lamina propria, downregulated myeloperoxidase activity, tumor necrosis factor-α, and caspase-3 activity, and lead to low mortality in response to I/R injury. On the contrary, CCK-2 receptor antagonist L365260 could markedly impair intestinal protection by gastrin on intestinal I/R. Severe edema of mucosal villi with severe intestinal crypt injury and numerous intestinal villi disintegrated were observed again in the hypergastrinemic rats with L365260. The survival in the hypergastrinemic rats after intestinal I/R injury was shortened by L365260. Finally, gastrin could remarkably upregulated intestinal CCK-2 receptor expression. Our data suggest that gastrin by omeprazole remarkably attenuated I/R induced intestinal injury by enhancing CCK-2 receptor expression and gastrin could be a potential mitigator for intestinal I/R damage in the clinical setting. PMID

  15. Autoantibody against diiodinated tyrosine-gastrin in a patient with Graves' disease

    SciTech Connect

    Noguchi, M.; Adachi, H.; Aoki, E.; Iida, Y.; Kasagi, K.; Endo, K.; Konishi, J.; Torizuka, K.

    1987-01-01

    We describe autoantibodies against iodinated gastrin in a patient with Graves' disease. Values for serum gastrin differed in this case, depending on which of two different radioimmunoassay (RIA) kits was used. RIA with the dextran-coated charcoal method for separation of free tracer gastrin gave a value less than 9.5 pmol/L, whereas the value by a RIA kit by the double-antibody method was 318 pmol/L. The patient's serum contained a binding protein for /sup 125/I-labeled gastrin, as detected by Sephadex G-200 column chromatography. The IgG fraction was responsible for the ability of serum to bind /sup 125/I-labeled gastrin. Interestingly, of the two possible forms of iodinated gastrins, monoiodinated (MIT) and diiodinated (DIT) tyrosine-/sup 125/I-labeled gastrin, only the latter bound to patient's IgG. Furthermore, DIT-gastrin, but not gastrin or MIT-gastrin, inhibited the binding of DIT-/sup 125/I-labeled gastrin. The patient's serum evidently contains autoantibodies against DIT-gastrin that interfere with RIA of gastrin.

  16. Complex morphology of gastrin-releasing G-cells in the antral region of the mouse stomach.

    PubMed

    Frick, Claudia; Rettenberger, Amelie Therese; Lunz, Malena Luisa; Breer, Heinz

    2016-11-01

    Gastrin-releasing enteroendocrine cells (G-cells) are usually described as flask-shaped cells with a large base and a small apical pole, integrated in the epithelium lining the basal region of the antral invaginations in the stomach. By means of a transgenic mouse line in which the enhanced version of GFP is endogenously expressed under the control of a gastrin promoter, we have analyzed the spatial distribution and morphological features of G-cells. We found that G-cells were not only located at the basal region of the invagination but to a lesser extent also at the upper region. Visualization of the entire cellular morphology revealed that G-cells show complex morphologies. Basally located G-cells are roundish-shaped cells which project a prominent apical process towards the lumen and extend basal protrusions containing the hormone gastrin that were frequently found in close proximity to blood vessels and occasionally in the vicinity of nerve fibers. Inspection of G-cells in the upper region of antral invaginations disclosed a novel population of G-cells. These cells have a spindle-like contour and long apical and basal processes which extend vertically along the antral invagination, parallel to the lumen. This G-cell population seems to be in contact with a network of nerve fibers. While the functional role of these untypical G-cells is still elusive, the results of this study provide some useful indications to possible roles of these G-cells.

  17. Role of proton pump inhibitors in preventing hypergastrinemia-associated carcinogenesis and in antagonizing the trophic effect of gastrin.

    PubMed

    Han, Y-M; Park, J-M; Kangwan, N; Jeong, M; Lee, S; Cho, J Y; Ko, W J; Hahm, K B

    2015-04-01

    Gastrin is the main hormone stimulating gastric acid secretion, but it exerts proliferative and anti-apoptotic actions on various cancer cell types, in addition to its well-known trophic effect on enterochromaffin-like cells. As treatment with proton pump inhibitors (PPIs) increases the biosynthesis and secretion of gastrin, it has been postulated that treatment with PPIs could increase the risk of cancer, especially in Barrett's esophagus, gastric carcinoids, and colorectal cancer (CRC). Some tumors produce gastrin of their own, which can act in an autocrine manner to promote tumor growth. In addition, gastrin is known to foster the tumor microenvironment. However, in spite of these potentially increased cancer risks due to PPI-induced hypergastrinemia, prospective, large-scale cohort studies did not show an increase in CRC prevalence. The question as to why the long-term use of PPIs was not associated with an increased cancer risk of CRC might be answered by the fact that the PPIs antagonized the trophic effects of hypergastrinemia. Furthermore, the blockade of proton pumps or potassium channels in cancer cells could limit the abnormal glycolytic energy metabolism of cancer cells. Apart from their suppressive effect on gastric acids, PPIs exert an anti-tumor effect through the selective induction of apoptosis as well as an anti-inflammatory effect, and they protect cells from developing chemo- or radiotherapeutic resistance. Moreover, the anti-carcinogenic actions of PPIs were augmented with PPI-induced hypergastrinemia. Together with their potential targeted killing of cancer stem cells, these effects demonstrate their potential anti-cancer actions.

  18. Calcium handling in porcine coronary endothelial cells by gastrin-17.

    PubMed

    Grossini, E; Molinari, C; Sigaudo, L; Biella, M; Mary, D A S G; Vacca, G

    2013-04-01

    In porcine coronary artery endothelial cells (PCAEC), gastrin-17 has recently been found to increase nitric oxide (NO) production by the endothelial NO synthase (eNOS) isoform through cholecystokinin 1/2 (CCK1/2) receptors and the involvement of protein kinase A (PKA), PKC and the β2-adrenoreceptor-related pathway. As eNOS is the Ca(2)(+)-dependent isoform of the enzyme, we aimed to examine the effects of gastrin-17 on Ca(2)(+) movements. Thus, experiments were performed in Fura-2-acetoxymethyl-ester-loaded PCAEC, where changes of cytosolic Ca(2)(+) ([Ca(2)(+)]c) caused by gastrin-17 were analysed and compared with those of CCK receptors and β2-adrenoreceptors agonists/antagonists. In addition, some experiments were performed by stimulating cells with gastrin-17 in the presence or absence of cAMP/PKA activator/inhibitor and of phospholipase C (PLC) and Ca(2)(+)-calmodulin dependent protein kinase II (CaMKII) blockers. The results have shown that gastrin-17 can promote a transient increase in [Ca(2)(+)]c mainly originating from an intracellular pool sensitive to thapsigargin and from the extracellular space. In addition, the response of cells to gastrin-17 was increased by the adenylyl cyclase activator and the β2-adrenoreceptor agonists and affected mainly by the CCK2 receptor agonists/antagonists. Moreover, the effects of gastrin-17 were prevented by β2-adrenoreceptors and CaMKII blockers and the adenylyl cyclase/PKA and PLC inhibitors. Finally, in PCAEC cultured in Na(+)-free medium or loaded with the plasma membrane Ca(2)(+) pump inhibitor, the gastrin-17-evoked Ca(2)(+) transient was long lasting. In conclusion, this study shows that gastrin-17 affected intracellular Ca(2)(+) homeostasis in PCAEC by both promoting a discharge of an intracellular pool and by interfering with the operation of store-dependent channels through mainly CCK2 receptors and PKA/PLC- and CaMKII-related signalling downstream of β2-adrenoreceptor stimulation.

  19. Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells.

    PubMed

    Chan, Chien-Pin; Tsai, Yao-Ting; Chen, Yao-Li; Hsu, Yu-Wen; Tseng, Joseph T; Chuang, Hung-Yi; Shiurba, Robert; Lee, Mei-Hsien; Wang, Jaw-Yuan; Chang, Wei-Chiao

    2015-02-01

    Divalent lead ions (Pb(2+) ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb(2+) from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb(2+) affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 μM lead nitrate. We found that Pb(2+) induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb(2+) . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb(2+) -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb(2+) also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb(2+) on gastrin gene activity in cell culture.

  20. Effect of colectomy on cholecystokinin and gastrin release.

    PubMed Central

    Inoue, K; Wiener, I; Fried, G M; Lilja, P; Watson, L C; Thompson, J C

    1982-01-01

    Studies were conducted to determine the effect of resection of the colon on the release of cholecystokinin (CCK) and gastrin. A standard food stimulation test was performed in five dogs. Peripheral blood samples were collected for future measurement of CCK and gastrin by specific radioimmunoassay. Each dog underwent subtotal colectomy with side-to-end ileoproctostomy. The food stimulation test was repeated at approximately weekly intervals for eight weeks after colectomy. Basal plasma CCK levels of 139 +/- 21 pg/ml before colectomy did not change after colectomy. Total amount CCK released after food was increased significantly at both four (5.94 +/- 0.78 ng min/ml) and eight (13.00 +/- 2.72 ng min/ml) weeks after colectomy in comparison with that observed prior to colectomy (2.94 +/- 0.54 ng min/ml). Basal serum gastrin levels of 28 +/- 9 pg/ml did not change significantly after colectomy. Total amount of gastrin released after food was increased significantly at both two (8651 +/- 2294 pg min/ml) and three (6940 +/- 1426 pg min/ml) weeks after operation, but at none of the later weeks. The precolectomy output, used for comparison, was 5608 +/- 1346 pg min/ml. It was concluded that resection of the colon leads to an increase in release of CCK and gastrin after food stimulation. This finding provides further evidence that the colon contains a factor that inhibits the release of CCK and gastrin, and that the colon functions as an endocrine organ. PMID:7149821

  1. Markov Model Predicts Changes in STH Prevalence during Control Activities Even with a Reduced Amount of Baseline Information

    PubMed Central

    Montresor, Antonio; Deol, Arminder; à Porta, Natacha; Lethanh, Nam; Jankovic, Dina

    2016-01-01

    Background Estimating the reduction in levels of infection during implementation of soil-transmitted helminth (STH) control programmes is important to measure their performance and to plan interventions. Markov modelling techniques have been used with some success to predict changes in STH prevalence following treatment in Viet Nam. The model is stationary and to date, the prediction has been obtained by calculating the transition probabilities between the different classes of intensity following the first year of drug distribution and assuming that these remain constant in subsequent years. However, to run this model longitudinal parasitological data (including intensity of infection) are required for two consecutive years from at least 200 individuals. Since this amount of data is not often available from STH control programmes, the possible application of the model in control programme is limited. The present study aimed to address this issue by adapting the existing Markov model to allow its application when a more limited amount of data is available and to test the predictive capacities of these simplified models. Method We analysed data from field studies conducted with different combination of three parameters: (i) the frequency of drug administration; (ii) the drug distributed; and (iii) the target treatment population (entire population or school-aged children only). This analysis allowed us to define 10 sets of standard transition probabilities to be used to predict prevalence changes when only baseline data are available (simplified model 1). We also formulated three equations (one for each STH parasite) to calculate the predicted prevalence of the different classes of intensity from the total prevalence. These equations allowed us to design a simplified model (SM2) to obtain predictions when the classes of intensity at baseline were not known. To evaluate the performance of the simplified models, we collected data from the scientific literature on

  2. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  3. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  4. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  5. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  6. 21 CFR 862.1325 - Gastrin test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gastrin test system. 862.1325 Section 862.1325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  7. Gastrin response to candidate messengers in intact conscious rats monitored by antrum microdialysis.

    PubMed

    Ericsson, Peter; Håkanson, Rolf; Norlén, Per

    2010-08-09

    We monitored gastrin release in response to locally applied candidate messengers in intact conscious rats. Earlier studies have been performed on anaesthetized animals, isolated pieces of antrum, or purified preparations of gastrin cells. In this study we created an experimental situation to resemble physiological conditions, using reverse microdialysis to administer regulatory peptides and amines that might affect gastrin secretion. Microdialysis probes were implanted in the submucosa of the antrum of the rat stomach. Three days later, putative messenger compounds were administered via the probe. Their effects on basal (24 h fast) and omeprazole-stimulated (400 micromol/kg/day, 4 days peroral administration) gastrin release were monitored by continuous measurement (3 h) of gastrin in the perfusate (radioimmunoassay). Fasted rats (low microdialysate gastrin, 2.1+/-0.1 pmol l(-1)) were used to study stimulation of gastrin release. Omeprazole-treated rats (high microdialysate gastrin, 95.8+/-6.7 pmol l(-1)) were used to study suppression of gastrin release. The following agents raised the concentration of microdialysate gastrin (peak response): gastrin-releasing peptide (GRP) (11-fold increase at a near-maximal dose), carbachol (5-fold increase), serotonin (2-fold increase) and isoprenaline (20-fold increase). Adrenaline and noradrenaline induced transient but powerful elevation (40- and 20-fold increase). Somatostatin, galanin and bradykinin (at near-maximal doses) suppressed omeprazole-stimulated gastrin release (50% decrease). Calcitonin gene-related peptide, ghrelin, gastric inhibitory peptide, motilin, neurotensin, neuromedin U-25, peptide YY and vasoactive intestinal peptide were without effect on gastrin release, as were aspartate, gamma-aminobutyric acid, glutamate, glycine, dopamine and histamine. The results support the view that G cells operate under neurocrine/paracrine control. They were stimulated by agents present in enteric neurons (GRP, galanin

  8. Molecular forms of gastrin in antral mucosa, plasma and gastric juice during vagal stimulation of anesthetized cats.

    PubMed

    Uvnäs-Wallensten, K; Rehfeld, J F

    1976-10-01

    Gastrin was released by electrical vagal stimulation in anesthetized cats. Antral mucosa, blood and gastric juice samples collected during vagal stimulation were subjected to gel filtration in order to characterize the different molecular forms of gastrin. In antral mucosa component III (gastrin-17) predominated. Besides, the antrum contained 5 per cent component II (gastrin-34, "big" gastrin), 1 per cent component I and trace amounts of component IV (gastrin-14 or "mini" gastrin). Immediately after vagal stimulation, component III (gastrin-17) appeared in the gastric venous effluent followed within a few minutes by component IV (gastrin-14). Component I and II (gastrin-34) were not detectable in any of the plasma samples. We suggest that component III (gastrin-17) is released from the antral mucosa and is then rapidly metabolized to component IV (gastrin-14) possibly to a significant extent in the fundic region of the stomach. Large amounts of component III (gastrin-17) were found in the vagally-induced gastric juice. Only very small amounts of degradation products were present, indicating that cat gastrin is relatively resistant to peptic degradation and acid hydrolysis.

  9. Follow-up study of gastrin response after resection of the jejunum and the ileum.

    PubMed Central

    Kajiwara, T; Tamura, K; Suzuki, T

    1977-01-01

    An experimental study was conducted on the effect of resection of the jejunum and ileum on gastrin release. The intravenous infusion of L. arginine in a dose of 0.5 g per kg body weight for 30 minutes proved to be most practical in evaluating gastrin release in addition to insulin and glucagon release. Serum gastrin levels in response to this dose of arginine were determined before and three weeks, three months and one year after resection of the jejunum and of the ileum. At three weeks, a significant increase in gastrin levels occurred in bothe the fasting state and after stimulation in dogs with either jejunum or ileum resection. At three months, the elevated gastrin response persisted only in those with jejunum resection. By one year, the gastrin levels had fallen in almost all dogs to approximately the preoperative levels. PMID:603274

  10. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies

    PubMed Central

    Smith, Jill P.; Fonkoua, Lionel K.; Moody, Terry W.

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin - responsive tumors. PMID:26929735

  11. The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies.

    PubMed

    Smith, Jill P; Fonkoua, Lionel K; Moody, Terry W

    2016-01-01

    The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin--responsive tumors.

  12. A feline case of hepatic neuroendocrine carcinoma with gastrin immunoreactivity.

    PubMed

    Kita, Chiaki; Yamagami, Tetsushi; Kinouchi, Shigemi; Nakano, Masayuki; Nagata, Nao; Suzuki, Hitomi; Ohtake, Yuzo; Miyoshi, Takuma; Irie, Mitsuhiro; Uchida, Kazuyuki

    2014-06-01

    A 5-year-old castrated Japanese domestic cat was presented with persistent vomiting. Ultrasound examinations revealed many masses only in the liver, and the fine needle aspiration was performed. Cytologically, polygonal or oval shaped tumor cells forming rosette and cord-like patterns were demonstrated, and then, the hepatic lesions were diagnosed as neuroendocrine carcinoma tentatively. The cat died one month after admission and was necropsied. Histopathologically, the tumor cells of the hepatic mass were arranged in typical rosette and cord-like structures. They were considerably uniform in size with hyperchromatic round nuclei and eosinophilic cytoplasm. Most of tumor cells were immunopositive for chromogranin A, and some were positive for gastrin. The findings indicate the possibility that the present case was a gastrin-producing neuroendocrine carcinoma.

  13. A Feline Case of Hepatic Neuroendocrine Carcinoma with Gastrin Immunoreactivity

    PubMed Central

    KITA, Chiaki; YAMAGAMI, Tetsushi; KINOUCHI, Shigemi; NAKANO, Masayuki; NAGATA, Nao; SUZUKI, Hitomi; OHTAKE, Yuzo; MIYOSHI, Takuma; IRIE, Mitsuhiro; UCHIDA, Kazuyuki

    2014-01-01

    ABSTRACT A 5-year-old castrated Japanese domestic cat was presented with persistent vomiting. Ultrasound examinations revealed many masses only in the liver, and the fine needle aspiration was performed. Cytologically, polygonal or oval shaped tumor cells forming rosette and cord-like patterns were demonstrated, and then, the hepatic lesions were diagnosed as neuroendocrine carcinoma tentatively. The cat died one month after admission and was necropsied. Histopathologically, the tumor cells of the hepatic mass were arranged in typical rosette and cord-like structures. They were considerably uniform in size with hyperchromatic round nuclei and eosinophilic cytoplasm. Most of tumor cells were immunopositive for chromogranin A, and some were positive for gastrin. The findings indicate the possibility that the present case was a gastrin-producing neuroendocrine carcinoma. PMID:24492315

  14. Interaction of a Swi3 homolog with Sth1 provides evidence for a Swi/Snf-related complex with an essential function in Saccharomyces cerevisiae.

    PubMed Central

    Treich, I; Carlson, M

    1997-01-01

    The Saccharomyces cerevisiae Swi/Snf complex has a role in remodeling chromatin structure to facilitate transcriptional activation. The complex has 11 components, including Swi1/Adr6, Swi2/Snf2, Swi3, Snf5, Snf6, Snf11, Swp73/Snf12, and Tfg3. Mammalian homologs of these proteins have been shown to form multiple Swi/Snf-related complexes. Here we characterize an S. cerevisiae Swi3 homolog (Swh3) and present evidence that it associates in a complex with a Snf2 homolog, Sthl. We identified Swh3 as a protein that interacts with the N terminus of Snf2 in the two-hybrid system. Swh3 and Swi3 are functionally distinct, and overexpression of one does not compensate for loss of the other. Swh3 is essential for viability and does not activate transcription of reporters. The Snf2 sequence that interacts with Swh3 was mapped to a region conserved in Sth1. We show that Swh3 and Sth1 fusion proteins interact in the two-hybrid system and coimmunoprecipitate from yeast cell extracts. We also map interactions between Swh3 and Sth1 and examine the role of a leucine zipper motif in self-association of Swh3. These findings, together with previous analysis of Sth1, indicate that Swh3 and Sth1 are associated in a complex that is functionally distinct from the Swi/Snf complex and essential for viability. PMID:9121424

  15. Nano-Localized Thermal Analysis and Mapping of Surface and Sub-Surface Thermal Properties Using Scanning Thermal Microscopy (SThM).

    PubMed

    Pereira, Maria J; Amaral, Joao S; Silva, Nuno J O; Amaral, Vitor S

    2016-12-01

    Determining and acting on thermo-physical properties at the nanoscale is essential for understanding/managing heat distribution in micro/nanostructured materials and miniaturized devices. Adequate thermal nano-characterization techniques are required to address thermal issues compromising device performance. Scanning thermal microscopy (SThM) is a probing and acting technique based on atomic force microscopy using a nano-probe designed to act as a thermometer and resistive heater, achieving high spatial resolution. Enabling direct observation and mapping of thermal properties such as thermal conductivity, SThM is becoming a powerful tool with a critical role in several fields, from material science to device thermal management. We present an overview of the different thermal probes, followed by the contribution of SThM in three currently significant research topics. First, in thermal conductivity contrast studies of graphene monolayers deposited on different substrates, SThM proves itself a reliable technique to clarify the intriguing thermal properties of graphene, which is considered an important contributor to improve the performance of downscaled devices and materials. Second, SThM's ability to perform sub-surface imaging is highlighted by thermal conductivity contrast analysis of polymeric composites. Finally, an approach to induce and study local structural transitions in ferromagnetic shape memory alloy Ni-Mn-Ga thin films using localized nano-thermal analysis is presented.

  16. Gastrin: from pathophysiology to cancer prevention and treatment.

    PubMed

    Maddalo, Gemma; Spolverato, Ylenia; Rugge, Massimo; Farinati, Fabio

    2014-07-01

    Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active 'adjuvant' treatment.

  17. Analysis of gastrin-releasing peptide gene and gastrin-releasing peptide receptor gene in patients with agoraphobia.

    PubMed

    Zimmermann, Katrin; Görgens, Heike; Bräuer, David; Einsle, Franziska; Noack, Barbara; von Kannen, Stephanie; Grossmann, Maria; Hoyer, Jürgen; Strobel, Alexander; Köllner, Volker; Weidner, Kerstin; Ziegler, Andreas; Hemmelmann, Claudia; Schackert, Hans K

    2014-10-01

    A gastrin-releasing peptide receptor (GRPR) knock-out mouse model provided evidence that the gastrin-releasing peptide (GRP) and its neural circuitry operate as a negative feedback-loop regulating fear, suggesting a novel candidate mechanism contributing to individual differences in fear-conditioning and associated psychiatric disorders such as agoraphobia with/without panic disorder. Studies in humans, however, provided inconclusive evidence on the association of GRP and GRPR variations in agoraphobia with/without panic disorder. Based on these findings, we investigated whether GRP and GRPR variants are associated with agoraphobia. Mental disorders were assessed via the Munich-Composite International Diagnostic Interview (M-CIDI) in 95 patients with agoraphobia with/without panic disorder and 119 controls without any mental disorders. A complete sequence analysis of GRP and GRPR was performed in all participants. We found no association of 16 GRP and 7 GRPR variants with agoraphobia with/without panic disorder.

  18. Sth1p, a Saccharomyces cerevisiae Snf2p/Swi2p homolog, is an essential ATPase in RSC and differs from Snf/Swi in its interactions with histones and chromatin-associated proteins.

    PubMed Central

    Du, J; Nasir, I; Benton, B K; Kladde, M P; Laurent, B C

    1998-01-01

    The essential Sth1p is the protein most closely related to the conserved Snf2p/Swi2p in Saccharomyces cerevisiae. Sth1p purified from yeast has a DNA-stimulated ATPase activity required for its function in vivo. The finding that Sth1p is a component of a multiprotein complex capable of ATP-dependent remodeling of the structure of chromatin (RSC) in vitro, suggests that it provides RSC with ATP hydrolysis activity. Three sth1 temperature-sensitive mutations map to the highly conserved ATPase/helicase domain and have cell cycle and non-cell cycle phenotypes, suggesting multiple essential roles for Sth1p. The Sth1p bromodomain is required for wild-type function; deletion mutants lacking portions of this region are thermosensitive and arrest with highly elongated buds and 2C DNA content, indicating perturbation of a unique function. The pleiotropic growth defects of sth1-ts mutants imply a requirement for Sth1p in a general cellular process that affects several metabolic pathways. Significantly, an sth1-ts allele is synthetically sick or lethal with previously identified mutations in histones and chromatin assembly genes that suppress snf/swi, suggesting that RSC interacts differently with chromatin than Snf/Swi. These results provide a framework for understanding the ATP-dependent RSC function in modeling chromatin and its connection to the cell cycle. PMID:9799253

  19. A Speculative Role for Stromal Gastrin Signaling in Development and Dissemination of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Matters, Gail L; Clawson, Gary A

    2013-01-01

    The peptide growth factor gastrin and its receptor, the G-protein coupled cholecystokinin receptor type B (CCKBR), play an integral role in the growth and progression of pancreatic ductal adenocarcinoma (PDAC). Gastrin immunoreactivity is found in the fetal pancreas but its expression is not detected in normal pancreas after birth, except when it is re-expressed in malignant lesions. PMID:25346875

  20. Contribution of gastrin to cysteamine-induced gastric acid secretion in rats.

    PubMed

    van de Brug, F J; Jansen, J B; Kuijpers, I J; Lamers, C B

    1993-01-01

    The role of circulating gastrin in cysteamine induced gastric acid secretion was examined in conscious male Wistar rats, provided with a portal vein catheter, a jugular vein catheter and a pyloric drainage tube. Intravenous infusion of 0.3 nmol/kg.30 min of gastrin 17-l resulted in serum gastrin concentrations of 1138 +/- 151 pg/ml and gastric acid secretion of 104 +/- 36 mumol H+/kg.30 min. This acid response was abolished by intravenous injection of 60 microliters of a gastrin-antiserum, indicating the efficacy of immunoneutralization with this antiserum in vivo. Intravenous bolus administration of 125 mg/kg of cysteamine induced increases in serum gastrin concentration (864 +/- 96 pg/ml) and gastric acid outputs (107 +/- 27 mumol H+/kg.30 min) not significantly different from the gastrin 17-l infusion experiments. Gastrin antiserum abolished cysteamine-induced gastric acid secretion, indicating that gastric acid secretion induced by 125 mg/kg of cysteamine is largely mediated by circulating gastrin in rats.

  1. Effect of cysteamine on secretion of gastrin and somatostatin from the rat stomach

    SciTech Connect

    McIntosh, C.; Bakich, V.; Trotter, T.; Kwok, Y.N.; Nishimura, E.; Pederson, R.; Brown, J.

    1984-05-01

    Cysteamine (beta-mercaptoethylamine HCl) administration to rats induces a hypergastrinemia and a reduction in gastric tissue somatostatin content. The possibility that this reduction may contribute to the elevated gastrin levels has been investigated in the isolated perfused rat stomach. Cysteamine (1 mM) rapidly increased immunoreactive gastrin release to levels ranging between 41% and 125% above basal. Increasing the dose to 10 mM caused a 1148% increase in immunoreactive gastrin. Secretion of somatosc immunoreactivity did not change. Perfusion of gastric inhibitory polypeptide (1 nM) induced a sustained increase in somatostatin like immunoreactivity secretion and a transient rise in gastrin. Addition of 10 mM cysteamine during gastric inhibitory polypeptide perfusion caused a 300% increase in immunoreactive gastrin. These levels were lower than in response to cysteamine alone. The results demonstrate that cysteamine can stimulate immunoreactive gastrin secretion without any change in somatostatinlike immunoreactivity release. When somatostatinlike immunoreactivity secretion is stimulated by an agent such as gastric inhibitory polypeptide, the cysteamine-induced release of immunoreactive gastrin is attenuated, suggesting the presence of a functional linkage between somatostatin and gastrin under these conditions.

  2. Induction of gastrin expression in gastrointestinal cells by hypoxia or cobalt is independent of hypoxia-inducible factor (HIF).

    PubMed

    Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2012-07-01

    Gastrin and its precursors have been shown to promote mitogenesis and angiogenesis in gastrointestinal tumors. Hypoxia stimulates tumor growth, but its effect on gastrin gene regulation has not been examined in detail. Here we have investigated the effect of hypoxia on the transcription of the gastrin gene in human gastric cancer (AGS) cells. Gastrin mRNA was measured by real-time PCR, gastrin peptides were measured by RIA, and gastrin promoter activity was measured by dual-luciferase reporter assay. Exposure to a low oxygen concentration (1%) increased gastrin mRNA concentrations in wild-type AGS cells (AGS) and in AGS cells overexpressing the gastrin receptor (AGS-cholecystokinin receptor 2) by 2.1 ± 0.4- and 4.1 ± 0.3-fold (P < 0.05), respectively. The hypoxia mimetic, cobalt chloride (300 μM), increased gastrin promoter activity in AGS cells by 2.4 ± 0.3-fold (P < 0.05), and in AGS-cholecystokinin receptor 2 cells by 4.0 ± 0.3-fold (P < 0.05), respectively. The observations that either deletion from the gastrin promoter of the putative binding sites for the transcription factor hypoxia-inducible factor 1 (HIF-1) or knockdown of either the HIF-1α or HIF-1β subunit did not affect gastrin promoter inducibility under hypoxia indicated that the hypoxic activation of the gastrin gene is likely HIF independent. Mutational analysis of previously identified Sp1 regulatory elements in the gastrin promoter also failed to abrogate the induction of promoter activity by hypoxia. The observations that hypoxia up-regulates the gastrin gene in AGS cells by HIF-independent mechanisms, and that this effect is enhanced by the presence of gastrin receptors, provide potential targets for gastrointestinal cancer therapy.

  3. Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis.

    PubMed

    Shao, Yun; Sun, Kun; Xu, Wei; Li, Xiao-Lin; Shen, Hong; Sun, Wei-Hao

    2014-09-28

    Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.

  4. Progress in developing cholecystokinin (CCK)/gastrin receptor ligands which have therapeutic potential

    PubMed Central

    Berna, Marc J.; Tapia, Jose A.; Sancho, Veronica; Jensen, Robert T.

    2007-01-01

    Summary Gastrin and CCK are two of the oldest hormones and within the last 15 years there has been an exponential increase in knowledge of their pharmacology, cell biology, receptors (CCK1R, CCK2R) and roles in physiology and pathological conditions. Despite these advances there is no approved disease indication for CCK receptor antagonists and only minor use of agonists. In this review the important factors determining this slow therapeutic development are reviewed. To assess this it is necessary to briefly review what is known about the roles of CCK receptors (CCK1R, CCK2R) in normal human physiology, their role in pathologic conditions, the selectivity of available potent CCKR agonists/antagonists as well as review their use in human conditions to date and the results. Despite extensive studies in animals and some in humans, recent studies suggest that monotherapy with CCK1R agonists will not be effective in obesity, nor CCK2R antagonists in panic disorders or CCK2R antagonists to inhibit growth of pancreatic cancer. Areas that require more study include the use of CCK2R agonists for imaging tumors and radiotherapy, CCK2R antagonists in hypergastrinemic states especially with long term PPI use and for potentiation of analgesia as well as use of CCK1R antagonists for a number of gastrointestinal disorders [motility disorders (irritable bowel syndrome, dyspepsia, constipation) and pancreatitis (acute, chronic)]. PMID:17997137

  5. In vivo analysis of mouse gastrin gene regulation in enhanced GFP-BAC transgenic mice

    PubMed Central

    Takaishi, Shigeo; Shibata, Wataru; Tomita, Hiroyuki; Jin, Guangchun; Yang, Xiangdong; Ericksen, Russell; Dubeykovskaya, Zinaida; Asfaha, Samuel; Quante, Michael; Betz, Kelly S.; Shulkes, Arthur

    2011-01-01

    Gastrin is secreted from a subset of neuroendocrine cells residing in the gastric antrum known as G cells, but low levels are also expressed in fetal pancreas and intestine and in many solid malignancies. Although past studies have suggested that antral gastrin is transcriptionally regulated by inflammation, gastric pH, somatostatin, and neoplastic transformation, the transcriptional regulation of gastrin has not previously been demonstrated in vivo. Here, we describe the creation of an enhanced green fluorescent protein reporter (mGAS-EGFP) mouse using a bacterial artificial chromosome that contains the entire mouse gastrin gene. Three founder lines expressed GFP signals in the gastric antrum and the transitional zone to the corpus. In addition, GFP(+) cells could be detected in the fetal pancreatic islets and small intestinal villi, but not in these organs of the adult mice. The administration of acid-suppressive reagents such as proton pump inhibitor omeprazole and gastrin/CCK-2 receptor antagonist YF476 significantly increased GFP signal intensity and GFP(+) cell numbers in the antrum, whereas these parameters were decreased by overnight fasting, octreotide (long-lasting somatostatin ortholog) infusion, and Helicobacter felis infection. GFP(+) cells were also detected in the anterior lobe of the pituitary gland and importantly in the colonic tumor cells induced by administration with azoxymethane and dextran sulfate sodium salt. This transgenic mouse provides a useful tool to study the regulation of mouse gastrin gene in vivo, thus contributing to our understanding of the mechanisms involved in transcriptional control of the gastrin gene. PMID:21051525

  6. Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria.

    PubMed Central

    Brand, S J; Stone, D

    1988-01-01

    Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells. Images PMID:2901431

  7. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors.

    PubMed

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe; Zhang, Chang Xian

    2015-10-01

    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors.

  8. In vivo analysis of mouse gastrin gene regulation in enhanced GFP-BAC transgenic mice.

    PubMed

    Takaishi, Shigeo; Shibata, Wataru; Tomita, Hiroyuki; Jin, Guangchun; Yang, Xiangdong; Ericksen, Russell; Dubeykovskaya, Zinaida; Asfaha, Samuel; Quante, Michael; Betz, Kelly S; Shulkes, Arthur; Wang, Timothy C

    2011-02-01

    Gastrin is secreted from a subset of neuroendocrine cells residing in the gastric antrum known as G cells, but low levels are also expressed in fetal pancreas and intestine and in many solid malignancies. Although past studies have suggested that antral gastrin is transcriptionally regulated by inflammation, gastric pH, somatostatin, and neoplastic transformation, the transcriptional regulation of gastrin has not previously been demonstrated in vivo. Here, we describe the creation of an enhanced green fluorescent protein reporter (mGAS-EGFP) mouse using a bacterial artificial chromosome that contains the entire mouse gastrin gene. Three founder lines expressed GFP signals in the gastric antrum and the transitional zone to the corpus. In addition, GFP(+) cells could be detected in the fetal pancreatic islets and small intestinal villi, but not in these organs of the adult mice. The administration of acid-suppressive reagents such as proton pump inhibitor omeprazole and gastrin/CCK-2 receptor antagonist YF476 significantly increased GFP signal intensity and GFP(+) cell numbers in the antrum, whereas these parameters were decreased by overnight fasting, octreotide (long-lasting somatostatin ortholog) infusion, and Helicobacter felis infection. GFP(+) cells were also detected in the anterior lobe of the pituitary gland and importantly in the colonic tumor cells induced by administration with azoxymethane and dextran sulfate sodium salt. This transgenic mouse provides a useful tool to study the regulation of mouse gastrin gene in vivo, thus contributing to our understanding of the mechanisms involved in transcriptional control of the gastrin gene.

  9. Menin and JunD regulate gastrin gene expression through proximal DNA elements.

    PubMed

    Mensah-Osman, Edith J; Veniaminova, Natalia A; Merchant, Juanita L

    2011-11-01

    Mutations in the MEN1 gene correlate with multiple endocrine neoplasia I (MEN1). Gastrinomas are the most malignant of the neuroendocrine tumors associated with MEN1. Because menin and JunD proteins interact, we examined whether JunD binds to and regulates the gastrin gene promoter. Both menin and JunD are ubiquitous nuclear proteins that we showed colocalize in the gastrin-expressing G cells of the mouse antrum. Transfection with a JunD expression vector alone induced endogenous gastrin mRNA in AGS human gastric cells, and the induction was blocked by menin overexpression. We mapped repression by menin to both a nonconsensus AP-1 site and proximal GC-rich elements within the human gastrin promoter. Chromatin immunoprecipitation assays, EMSAs, and DNA affinity precipitation assays documented that JunD and Sp1 proteins bind these two elements and are both targets for menin regulation. Consistent with menin forming a complex with histone deacetylases, we found that repression of gastrin gene expression by menin was reversed by trichostatin A. In conclusion, proximal DNA elements within the human gastrin gene promoter mediate interactions between JunD, which induces gastrin gene expression and menin, which suppresses JunD-mediated activation.

  10. Evidence for a significant role of gastrin in cysteamine-induced hypersecretion of gastric acid.

    PubMed

    Shiratori, K; Shimizu, K; Ikeda, M; Watanabe, S; Hayashi, N

    1997-01-01

    Cysteamine has been known to stimulate gastric acid secretion and to induce duodenal ulcers in rats. We investigated the role of gastrin in cysteamine-induced acid hypersecretion in the perfused rat stomach. Intravenous infusion of cysteamine (75 mg/kg/h) resulted in a significant increase in acid secretion, which was accompanied by a marked increase in the plasma gastrin concentration. The cysteamine-induced increase in gastric acid secretion was completely blocked by i.v. injection of anti-gastrin rabbit serum (500 microliters). In addition, i.v. infusion of a CCK-B/gastrin receptor antagonist (L-365,260) (1 mg/kg/h) also suppressed the cysteamine-induced increase in acid secretion. Atropine significantly, but only partially, inhibited the increase. The elevated plasma gastrin levels induced by cysteamine were unaffected by atropine and L-365,260. In conclusion, cysteamine-induced acid hypersecretion is mediated mainly by cysteamine-induced gastrin release and partially by cholinergic factors. Furthermore, gastrin release caused by cysteamine appears to be independent of cholinergic tone.

  11. Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells.

    PubMed

    Norlén, P; Kitano, M; Lindström, E; Håkanson, R

    2000-06-01

    By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is associated with suppressed ECL-cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid-producing part of the stomach (32 rats). Three days later, ECL-cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), urethane (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg(-1)). In a parallel series of experiments, basal- and gastrin-induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55 - 80%. The reduction in gastrin-induced acid response (70 - 95%) was strongly correlated to the reduction in gastrin-induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin-evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exception of urethane, they inhibited gastrin

  12. Cyclic nucleotides of canine antral smooth muscle. Effects of acetylcholine, catecholamines and gastrin.

    PubMed

    Baur, S; Grant, B; Wooton, J

    1981-01-07

    1. The effects of acetylcholine, catecholamines and gastrin on the intracellular content of cyclic AMP and cyclic GMP in antral circular muscle have been determined. 2. Acetylcholine results in a significant but transient increase in intracellular cyclic GMP. 3. Isoproterenol and norepinephrine increase intracellular cyclic AMP. Based on half-maximal effective doses, isoproterenol is 2.7-times more effective than norepinephrine. The increase in intracellular cyclic AMP by both agents is inhibited by propranolol but not phentolamine, indicating that both agents act on the muscle cell by a beta-receptor-coupled mechanism. 4. Gastrin has no demonstrable effect on either cyclic AMP or cyclic GMP. This suggests that while gastrin and acetylcholine can produce a like myoelectric response in the muscle cell, the action of gastrin is mediated by a separate receptor, presumably on the muscle cell, and not by a release of acetylcholine.

  13. An expedient route to a potent gastrin/CCK-B receptor antagonist (+)-AG-041R.

    PubMed

    Sato, Shigeki; Shibuya, Masatoshi; Kanoh, Naoki; Iwabuchi, Yoshiharu

    2009-10-02

    An enantiocontrolled synthesis of (+)-AG-041R (1), a potent gastrin/CCK-B receptor antagonist, has been achieved employing a chiral rhodium(II)-catalyzed, oxidative intramolecular aza-spiroannulation as the key step.

  14. Structure-activity relationships of C-terminal tri- and tetrapeptide fragments that inhibit gastrin activity.

    PubMed

    Martinez, J; Bali, J P; Magous, R; Laur, J; Lignon, M F; Briet, C; Nisato, D; Castro, B

    1985-03-01

    A series of tri- and tetrapeptide derivatives, analogues of the gastrin C-terminal region with no phenylalanine residue, were synthesized. These peptides were tested for their ability to inhibit gastrin-stimulated acid secretion in vivo as well as binding of [125I]-(Nle11)-HG-13 to gastric mucosal cell receptors in vitro. Most of the peptides tested exhibited gastrin antagonist activity in vivo and in vitro. Most active derivatives were 20-30 times more potent than the well-known gastrin antagonist derivatives proglumide and benzotript and had 20-200 times more binding affinity. The smallest fragment exhibiting antagonist activity was the tripeptide Boc-L-tryptophyl-L-methionyl-L-aspartic acid amide.

  15. Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric epithelial cells.

    PubMed

    Nørsett, Kristin G; Steele, Islay; Duval, Cedric; Sammut, Stephen J; Murugesan, Senthil V M; Kenny, Susan; Rainbow, Lucille; Dimaline, Rod; Dockray, Graham J; Pritchard, D Mark; Varro, Andrea

    2011-09-01

    Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression, fibrosis and thrombosis. It is expressed in the stomach but the mechanisms controlling its expression there, and its biological role, are uncertain. We sought to define the role of gastrin in regulating PAI-1 expression and to determine the relevance for gastrin-stimulated cell migration and invasion. In gastric biopsies from subjects with elevated plasma gastrin, the abundances of PAI-1, urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNAs measured by quantitative PCR were increased compared with subjects with plasma concentrations in the reference range. In patients with hypergastrinemia due to autoimmune chronic atrophic gastritis, there was increased abundance of PAI-1, uPA, and uPAR mRNAs that was reduced by octreotide or antrectomy. Immunohistochemistry revealed localization of PAI-1 to parietal cells and enterochromaffin-like cells in micronodular neuroendocrine tumors in hypergastrinemic subjects. Transcriptional mechanisms were studied by using a PAI-1-luciferase promoter-reporter construct transfected into AGS-G(R) cells. There was time- and concentration-dependent increase of PAI-1-luciferase expression in response to gastrin that was reversed by inhibitors of the PKC and MAPK pathways. In Boyden chamber assays, recombinant PAI-1 inhibited gastrin-stimulated AGS-G(R) cell migration and invasion, and small interfering RNA treatment increased responses to gastrin. We conclude that elevated plasma gastrin concentrations are associated with increased expression of gastric PAI-1, which may act to restrain gastrin-stimulated cell migration and invasion.

  16. [Changes of plasma endocrine hormone in pilots under Coriolis acceleration].

    PubMed

    Dai, Y; Ji, G; Huang, Y; Sun, X; Dai, F

    1998-04-01

    Plasma endocrine hormones were studied in both 24 motion sickness (orthostatic intolerance) and healthy pilots. Coriolis acceleration of 3.75, 5.00 and 6.25 pi 2 cm/s2 were given with intervals of 3-4 min AT-II, insulin, cortisol, Aldosterone and gastrin were determined by radioimmunoassay. It was found that aldosterone, AT-II, gastrin increased with increase of coriolis acceleration in all pilots. (P < 0.05), but cortisol and insulin only increased in healthy pilots (P < 0.05). It suggests excitation of the autonomic nervous system might be insufficient in orthostatic intolerant pilots and that determination of endocrine hormones may be useful in the evaluation of autonomic nervous activities.

  17. Induction of follistatin precedes gastric transformation in gastrin deficient mice

    SciTech Connect

    Kang Weiqun; Saqui-Salces, Milena; Zavros, Yana; Merchant, Juanita L.

    2008-11-21

    We previously showed that antral gastric tumors develop in gastrin-deficient (Gas{sup -/-}) mice. Therefore Gas{sup -/-}mice were studied sequentially over 12 months to identify molecular mechanisms underlying gastric transformation. Fundic atrophy developed by 9 months in Gas{sup -/-} mice. Antral mucosal hyperplasia developed coincident with the focal loss of TFF1 and Muc5AC. Microarray analysis of 12 month Gas{sup -/-} tumors revealed an increase in follistatin, an activin/BMP antagonist. We found that elevated follistatin expression occurred in the proliferative neck zone of hyperplastic antrums, in antral tumors of Gas{sup -/-} mice, and also in human gastric cancers. Follistatin induced cyclin D1 and the trefoil factors TFF1 and TFF2 in a gastric cancer cell line. We concluded that antral hyperplasia in Gas{sup -/-} mice involves amplification of mucous cell lineages due to follistatin, suggesting its role in the development of antral gastric tumors.

  18. Gastrin promotes intestinal polyposis through cholecystokinin-B receptor-mediated proliferative signaling and fostering tumor microenvironment.

    PubMed

    Han, Y-M; Park, J-M; Park, S-H; Hahm, K B; Hong, S P; Kim, E-H

    2013-08-01

    Increased serum gastrin concentrations in patients with colorectal cancer suggested the tumorigenic trophic effect of gastrin. Detailed and global molecular mechanisms explaining trophic effect of gastrin had not been revealed. In the current study, intestinal polyposis of APC(Min/⁺) mice was compared between phosphate buffered saline (PBS) injected and gastrin (10 μg/kg, thrice per week) injected group. Total number of intestinal polyposis was counted and immunohistochemical staining with F4/80 and CD3 was done. MTT assay, cell cycle analysis, and Western blot for cyclin D1, CDK4, and β-catenin were performed in Raw 264.7 and HCT116 cells before and after gastrin administration. Experiments were repeated with YM022 or transfection with si-cholecystokinin-B receptor (CCK-B-R). Intraperitoneal gastrin significantly increased intestinal polyposis in APC(Min/⁺) mice (P<0.005), in which significant increases in macrophage were noted on F4/80 immunohistochemical staining (Plt;0.05) as well as Ki-67 staining (Plt;0.05) after gastrin. On comparative cytokine array, gastrin increased interleukin-1β (IL-1β), interleukin 3Rβ (IL-3Rβ), stromal cell-derived factor-1α (SDF-1α), thymus and activation-regulated chemokine (TARC), and thymus-derived chemotactic agent 3 (TCA-3) in macrophage cells, which was further confirmed with real time polymerase chain reaction (RT-PCR) analysis (P<0.05). In addition to increased inflammatory cytokines, gastrin increased macrophage proliferation accompanied with increased cyclin D1 and CDK4. Targeted for HCT116 cells, gastrin significantly increased proliferation as well as increases in synthetic phase of cell cycle. YM022 as gastrin antagonist significantly abolished the trophic actions of gastrin (P<0.05). HCT116 cells transfected with siCCK-B-R, gastrin did not increase either cell cycle or β-catenin in spite of gastrin administration. Conclusively, gastrin promoted intestinal polyposis through either direct gastrin receptor

  19. Long-term outcome of stapled transanal rectal resection (STARR) versus stapled hemorrhoidopexys (STH) for grade III-IV hemorrhoids: preliminary results.

    PubMed

    Zanella, Simone; Spirch, Saverio; Scarpa, Marco; Ricci, Francesco; Lumachi, Franco

    2014-01-01

    Circular stapled transanal hemorrhoidopexy (STH) was first introduced by A. Longo for the correction of internal mucosal prolapse and obstructed defecation and in 1998, was proposed as alternative to conventional excisional hemorrhoidectomy. More recently, stapled transanal rectal resection (STARR) has gradually gained popularity, as the Longo procedure, in the treatment of hemorrhoids. The aim of our study was to evaluate the usefulness of STARR as alternative to STH in patients with grade III (n=218, 68.1%) and IV (n=102, 31.9%) hemorrhoids. A group of 320 consecutive patients (median age=51 years; range=16-85) underwent STH (n=281) or STARR (n=39) procedure. The rate of postoperative bleeding (53.8% vs. 74.4%, p<0.01) was significantly reduced in patients who underwent STARR procedure, which required a longer (45 ± 22 vs. 26 ± 11 min, p<0.01) operative time. There were no differences between groups with regard to use of painkillers, postoperative pain intensity, short- (three months) and long-term (one and three years) residual pain, soiling, incontinence and urgency. Patients treated with the STARR procedure had lower recurrence rate of hemorrhoids and a lower incidence of prolapse, both at one year (none vs. 1.4%, p=0.593 and 2.6% vs. 5.3%, p=0.396, respectively) and at two years (none vs. 6.8%, p=0.078 and none vs. 13.2%, p=0.012, respectively). The one-year (9.0 ± 1.8 vs. 9.4 ± 0.7, p=0.171) and two-year (9.6 ± 0.8 vs. 9.1 ± 1.7, p=0.072) general satisfaction was similar but higher in STARR patients than in the STH group. In conclusion, according to our preliminary results, the STARR procedure leads to a lower incidence of complications and recurrences and should be considered for patients with grade III or IV hemorrhoids previously selected for stapled hemorrhoidectomy, as a promising alternative to STH.

  20. Pure Human Big Gastrin IMMUNOCHEMICAL PROPERTIES, DISAPPEARANCE HALF TIME, AND ACID-STIMULATING ACTION IN DOGS

    PubMed Central

    Walsh, John H.; Debas, Haile T.; Grossman, Morton I.

    1974-01-01

    Biological properties of pure natural human “big gastrin” (designated G-34 because it contains 34 amino acid residues) were compared with those of pure natural heptadecapeptide gastrins (G-17) from human and porcine sources. Radioimmunoassay inhibition curves indicated that G-17 was nearly 1.5 times more potent than G-34 with the antibody used in this study. This difference was confirmed by demonstration of increased immunoreactivity generated when G-34 was converted to G-17 by trypsinization. When infused intravenously into dogs with gastric fistulas and Heidenhain pouches in equimolar doses, G-34 produced slightly higher acid secretory responses than G-17. Responses to sulfated and nonsulfated forms were not significantly different, nor were responses to human and porcine G-17. During infusion of equimolar doses, steady-state serum gastrin concentrations were more than fivefold higher with G-34 than with G-17. The difference in steady-state blood concentrations could be accounted for by a corresponding difference in removal rates. The half times of the G-34 preparations averaged 15.8 min and the half times of the G-17 preparations averaged 3.2 min. The calculated spaces of distribution for G-17 and G-34 were similar, about 25% of body weight. When the increment in serum gastrin was plotted against acid secretory response it was found that nearly five times greater increments in molar concentrations of G-34 than of G-17 were required to produce the same rate of acid secretion. The potency of these two molecular forms of gastrin can be expressed in two different ways. Based on exogenous molar doses, the potencies of G-34 and G-17 were similar. However, based on molar increments in serum gastrin concentration, G-17 was approximately five times more potent than G-34. Hence, fractionation of these gastrin components may be important in estimation of the acid-stimulating action represented by total serum gastrin as measured by radio-immunoassay. PMID:4847254

  1. Unsulfated cholecystokinin: An overlooked hormone?

    PubMed

    Rehfeld, Jens F; Agersnap, Mikkel

    2012-01-10

    Tyrosyl O-sulfation is a common posttranslational derivatization of proteins that may also modify regulatory peptides. Among these are members of the cholecystokinin (CCK)/gastrin family. While sulfation of gastrin peptides is without effect on the bioactivity, O-sulfation is crucial for the cholecystokinetic activity (i.e. gallbladder emptying) of CCK peptides. Accordingly, the purification of CCK as a sulfated peptide was originally monitored by its gallbladder emptying effect. Since then, the dogma has prevailed that CCK peptides are always sulfated. The dogma is correct in a semantic context since the gallbladder expresses only the CCK-A receptor that requires sulfation of the ligand. CCK peptides, however, are also ligands for the CCK-B receptors that do not require ligand sulfation. Consequently, unsulfated CCK peptides may act via CCK-B receptors. Since in vivo occurrence of unsulfated products of proCCK with an intact α-amidated C-terminal tetrapeptide sequence (-Trp-Met-Asp-PheNH(2)) has been reported, it is likely that unsulfated CCK peptides constitute a separate hormone system that acts via CCK-B receptors. This review discusses the occurrence, molecular forms, and possible physiological as well as pathophysiological significance of unsulfated CCK peptides.

  2. Retro-inverso forms of gastrin5-12 are as biologically active as glycine-extended gastrin in vitro but not in vivo.

    PubMed

    Marshall, Kathryn M; Laval, Marie; Sims, Ioulia; Shulkes, Arthur; Baldwin, Graham S

    2015-12-01

    Non-amidated gastrin peptides such as glycine-extended gastrin (Ggly) are biologically active in vitro and in vivo and have been implicated in the development of gastric and colonic cancers. Previous studies have shown that the truncated form of Ggly, the octapeptide LE5AY, was still biologically active in vitro, and that activity was dependent on ferric ion binding but independent of binding to the cholecystokinin 2 (CCK2) receptor. The present work was aimed at creating more stable gastrin-derived 'super agonists' using retro-inverso technology. The truncated LE5AY peptide was synthesized using end protecting groups in three forms with l-amino acids (GL), d-amino acids (GD) or retro-inverso (reverse order with d-amino acids; GRI). All of these peptides bound ferric ions with a 2:1 (Fe: peptide) ratio. As predicted, Ggly, GL and GRI were biologically active in vitro and increased cell proliferation in mouse gastric epithelial (IMGE-5) and human colorectal cancer (DLD-1) cell lines, and increased cell migration in DLD-1 cells. These activities were likely via the same mechanism as Ggly since no CCK1 or CCK2 binding was identified, and GD remained inactive in all assays. Surprisingly, unlike Ggly, GL and GRI were not active in vivo. While Ggly stimulated colonic crypt height and proliferation rates in gastrin knockout mice, GL and GRI did not. The apparent lack of activity may be due to rapid clearance of these smaller peptides. Nevertheless further work designing and testing retro-inverso gastrins is warranted, as it may lead to the generation of super agonists that could potentially be used to treat patients with gastrointestinal disorders with reduced mucosal function.

  3. Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells.

    PubMed

    Singh, P; Wu, H; Clark, C; Owlia, A

    2007-01-18

    We and others have reported the presence of novel progastrin (PG)/gastrin receptors on normal and cancerous intestinal cells. We had earlier reported the presence of 33-36 kDa gastrin-binding proteins on cellular membranes of colon cancer cells. The goal of the current study was to identify the protein(s) in the 33-36 kDa band, and analyse its functional significance. A carbodiimide crosslinker was used for crosslinking radio-labeled gastrins to membrane proteins from gastrin/PG responsive cell lines. Native membrane proteins, crosslinked to the ligand, were solubulized and enriched by >1000-fold, and analysed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. The peptide masses were researched against the NCBInr database using the ProFound search engine. Annexin II (ANX II) was identified, and confirmed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. As HCT-116 cells express autocrine PG, the in situ association of PG with ANX II was demonstrated in pulldown assays. Direct binding of PG with ANX II was confirmed in an in vitro binding assay. In order to confirm a functional importance of these observations, sense and anti-sense (AS) ANX II RNA-expressing clones of intestinal epithelial (IEC-18) and human colon cancer (HCT-116) cell lines were generated. AS clones demonstrated a significant loss in the growth response to exogenous (IEC-18) and autocrine (HCT-116) PG. We have thus discovered that membrane-associated ANX II binds PG/gastrins, and partially mediates growth factor effects of the peptides.

  4. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    PubMed

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

  5. Hormonal status and fluid electrolyte metabolism in motion sickness

    SciTech Connect

    Grigoriev, A.I.; Nichiporuk, I.A.; Yasnetsov, V.V.; Shashkov, V.S.

    1988-04-01

    In the first experimental series, 10 healthy male test subjects with a high susceptibility to motion sickness showed a significant increase of ACTH, cortisol, STH, prolactin, ADH, aldosterone concentrations, and plasma renin activity after vestibular tests. The 10 subjects with a moderate susceptibility exhibited a still higher increase of the hormones, except plasma renin. The 8 test subjects with a low susceptibility displayed a considerable increase in ACTH, cortisol, and STH after vestibular stimulation. In the second experimental series, the increase of STH, cortisol, ADH, aldosterone and renin occurred immediately after rotation in the moderate susceptibility subjects and an hour after exposure in the high susceptibility subjects. This may be indicative of specific immediate adaptation mechanisms or excitation transfer in the CNS in high susceptibility persons. In the third experimental animal series, the permeability of the blood-brain barrier for /sup 125/I and IgG increased after rotation. Greater concentrations of potassium, chloride, and urea in CSF are suggestive of an inhibition process activation in the CNS and, probably, of an active urea transport by the vascular plexus epithelium which maintains constant osmotic pressure of cerebral extracellular fluid and prevents hyper-hydration of CNS neurons.

  6. The role of endogenous gastrin in the development of enterochromaffin-like cell carcinoid tumors in Mastomys natalensis: a study with the specific gastrin receptor antagonist AG-041R.

    PubMed

    Chiba, T; Kinoshita, Y; Sawada, M; Kishi, K; Baba, A; Hoshino, E

    1998-01-01

    We examined the effects of a newly synthesized gastrin receptor antagonist, AG-041R, on the growth of enterochromaffin-like (ECL) carcinoid tumors in Mastomys natalensis both in vitro and in vivo. AG-041R was as potent as the well known gastrin antagonist L365,260 in inhibiting not only the gastrin-induced release of histamine from but also histidine decarboxylase (HDC) gene expression in the ECL carcinoid tumor cells. AG-041R also inhibited gastrin-induced DNA synthesis and c-fos gene expression in the tumor cells. Furthermore, AG-041R significantly inhibited the growth of the transplanted Mastomys ECL carcinoid tumors in vivo. From these data, it is concluded that endogenous gastrin is involved in the growth of ECL carcinoid tumors in Mastomys natalensis. Moreover, AG-041R is shown to have a potential as an anti-neoplastic agent for ECL carcinoid tumor of the stomach.

  7. The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis

    PubMed Central

    Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

    2016-01-01

    Abstract A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG). An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs). Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45–0.51) and 0.79 (95% CI: 0.77–0.81), respectively. The DOR was 5.93 (95% CI: 2.93–11.99), and the AUC was 0.82. G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future. PMID:27149493

  8. Gastrin-releasing peptide stimulates glycoconjugate release from feline trachea

    SciTech Connect

    Lundgren, J.D.; Baraniuk, J.N.; Ostrowski, N.L.; Kaliner, M.A.; Shelhamer, J.H. )

    1990-02-01

    The effect of gastrin-releasing peptide (GRP) on respiratory glycoconjugate (RGC) secretion was investigated in a feline tracheal organ culture model. RGC secretion was stimulated by GRP in a dose-dependent fashion at concentrations from 10(-8) to 10(-5) M (range 15-38% increase above control) with a peak effect within 0.5-1 h of incubation. GRP-(14-27), the receptor binding portion of GRP, and the related molecule, bombesin, also stimulated RGC secretion by approximately 20% above control. Acetyl-GRP-(20-27) stimulated RGC release by 10%, whereas GRP-(1-16) was inactive. Autoradiographic studies with 125I-GRP revealed that specific binding was restricted to the submucosal glands and the surface epithelium. A specific radioimmunoassay showed the content of GRP in feline trachea after extraction with ethanol-acetic acid to be 156 +/- 91 fmol/g wet wt. Indirect immunohistochemistry indicated that ganglion cells located just outside the cartilage contained GRP-immunoreactive materials. GRP is a novel mucus secretagogue that may participate in regulating airway mucosal gland secretion.

  9. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  10. Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitro.

    PubMed

    Kovac, Suzana; Ferrand, Audrey; Estève, Jean-Pierre; Mason, Anne B; Baldwin, Graham S

    2009-09-01

    Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin-gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin-ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8-10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo.

  11. Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo.

    PubMed

    Marshall, Kathryn M; Laval, Marie; Estacio, Ortis; Hudson, Damien F; Kalitsis, Paul; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2015-10-01

    Over-expression of growth factors can contribute to the development and progression of cancer, and gastrins in particular have been implicated in accelerating the development of gastrointestinal cancers. Previously our group showed that hypoxia, cobalt chloride (a hypoxia mimetic) and zinc chloride could activate the expression of the gastrin gene in vitro. To characterise activation of the gastrin promoter by zinc ions further in vivo, TALEN technology was used to engineer a luciferase reporter construct into the endogenous human gastrin gene promoter in SW480 colon cancer cells. Gastrin promoter activity in the resultant Gast(luc) SW480 colon cancer cells was then measured by bioluminescence in cell culture and in tumour xenografts in SCID mice. Activation of intracellular signalling pathways was assessed by Western blotting. Activation of the gastrin promoter by zinc ions was concentration dependent in vitro and in vivo. Zinc ions significantly stimulated phosphorylation of ERK1/2 (MAPK pathway) but not of Akt (PI3K pathway). We conclude that the endogenous gastrin promoter is responsive to zinc ions, likely via activation of the MAPK pathway.

  12. Synthesis of gastrin antagonists, analogues of the C-terminal tetrapeptide of gastrin, by introduction of a beta-homo residue.

    PubMed

    Rodriguez, M; Fulcrand, P; Laur, J; Aumelas, A; Bali, J P; Martinez, J

    1989-03-01

    A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.

  13. Effect of green tea catechins on gastric mucosal dysplasia in insulin-gastrin mice.

    PubMed

    Ohno, Takashi; Ohtani, Masahiro; Suto, Hiroyuki; Ohta, Makoto; Imamura, Yoshiaki; Matsuda, Hidetaka; Hiramatsu, Katsushi; Nemoto, Tomoyuki; Nakamoto, Yasunari

    2016-06-01

    Green tea catechins (GTCs) have been implicated in various physiological effects, including anti-carcinogenic activities. In the present study, we evaluated the effects of GTCs specifically on the development of gastritis and pre-malignant lesions in insulin-gastrin mice. Nine-week-old male INS-GAS mice (n=38) were supplemented with GTCs for 4 and 28 weeks, and their body weights, serum gastrin levels, histopathology and pro-inflammatory cytokine levels in gastric tissue and mucosal cell proliferation were monitored. Body weights of the GTC-treated mice were significantly lower than those of the untreated controls (P≤0.05). Serum gastrin levels were suppressed at the age of 37-weeks (P≤0.05). The histopathological scores indicated that the extent of dysplasia was significantly diminished (P≤0.05), although GTC supplementation did not affect the inflammation scores. The messenger RNA levels of interferon (IFN)-γ were significantly reduced at the age of 13 weeks (P≤0.05), although the changes did not reach statistical significance at the age of 37 weeks (P=0.056). The labeling index of Ki-67 immunohistochemistry was significantly decreased (P≤0.05). These results demonstrated that GTCs may play a protective role in the development of gastritis and pre-malignant lesions via an IFN-γ, gastrin, and mucosal cell proliferation-dependent mechanism in this rodent model and potentially in humans.

  14. Activation of the calcium sensing receptor with cinacalcet increases serum gastrin levels in healthy older subjects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastric acidity is postulated to enhance calcium absorption since calcium is better dissolved at low pH. Extracellular calcium stimulates gastrin and gastric acid secretion in humans. Ex vivo studies indicate that the calcium sensing receptor (CaR), which is expressed on the surface of human G cells...

  15. Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

    PubMed Central

    Fraser, A G; Lam, W M; Luk, Y W; Sercombe, J; Sawyerr, A M; Hudson, M; Samloff, I M; Pounder, R E

    1993-01-01

    Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate. PMID:8472980

  16. Increased gastrin gene expression provides a physiological advantage to mice under hypoxic conditions.

    PubMed

    Laval, Marie; Baldwin, Graham S; Shulkes, Arthur; Marshall, Kathryn M

    2015-01-15

    Hypoxia, or a low concentration of O2, is encountered in humans undertaking activities such as mountain climbing and scuba diving and is important pathophysiologically as a limiting factor in tumor growth. Although data on the interplay between hypoxia and gastrins are limited, gastrin expression is upregulated by hypoxia in gastrointestinal cancer cell lines, and gastrins counterbalance hypoxia by stimulating angiogenesis in vitro and in vivo. The aim of this study was to determine if higher concentrations of the gastrin precursor progastrin are protective against hypoxia in vivo. hGAS mice, which overexpress progastrin in the liver, and mice of the corresponding wild-type FVB/N strain were exposed to normoxia or hypoxia. Iron status was assessed by measurement of serum iron parameters, real-time PCR for mRNAs encoding critical iron regulatory proteins, and Perls' stain and atomic absorption spectrometry for tissue iron concentrations. FVB/N mice lost weight at a faster rate and had higher sickness scores than hGAS mice exposed to hypoxia. Serum iron levels were lower in hGAS than FVB/N mice and decreased further when the animals were exposed to hypoxia. The concentration of iron in the liver was strikingly lower in hGAS than FVB/N mice. We conclude that increased circulating concentrations of progastrin provide a physiological advantage against systemic hypoxia in mice, possibly by increasing the availability of iron stores. This is the first report of an association between progastrin overexpression, hypoxia, and iron homeostasis.

  17. Gastrin, gastric acid secretion, and gastric microflora in patients with rheumatoid arthritis.

    PubMed Central

    Henriksson, K; Uvnäs-Moberg, K; Nord, C E; Johansson, C; Gullberg, R

    1986-01-01

    The relation between the basal and stimulated gastric acid secretion, plasma gastrin, and the gastric microflora was examined in 45 patients with rheumatoid arthritis. Sixteen patients (36%) had basal achlorhydria, and of these, 10 (22%) had achlorhydria or hypochlorhydria after stimulation with pentagastrin. The peak acid output and acidity showed inverse correlation with the disease duration but were not associated with age or with the degree of physical disability. Hypergastrinaemia was found in nine patients (20%), of whom 6 (13%) had significant titres of parietal cell antibody. The acidity of the peak acid output showed negative correlation with plasma gastrin. It was confirmed that the gastric secretory state is a determinant of plasma gastrin levels and in addition influences the growth of micro-organisms in the gastric lumen. The type of microflora in the non-acid stomach was similar to that found in the saliva. A subgroup of eight females was identified who showed low gastric acid secretion rates, positive bacterial cultures, and atlantoaxial subluxation. Gastrin- and insulin-like immunoreactivities were found in joint fluid. The concentrations reflected their plasma levels, suggesting that the peptides are not released at the inflammatory site, but rather that they reach synovial fluid from circulating blood. PMID:3524480

  18. Role of Vitamin D on the Inhibition of Gastrin Production After Cisplatin Treatment

    PubMed Central

    Wang, Ying; Kopachik, Will

    2000-01-01

    In rats cisplatin induces hypocalcemia, bloating of the stomach, and ulceration ameliorated through calcium supplements. This study was undertaken to test the role of calcium on the gastrin mRNA production in vitro and in vivo. RIN B6 cells were cultured in medium with calcium (1.8, 3.6 and 7.2 mM) and the active form of vitamin D (calcijex). Cisplatin was added (10 μg/ml) for 12 hrs and cells were harvested for RNA from various treatment groups. Male Wistar rats were treated with cisplatin (9 mg/kg), before and after vitamin D (0.3 mg/100g/week). The rats were killed and stomach tissues excised on 1, 6, 10 and 15 days after cisplatin treatment. RNA from the stomach was analyzed using the northern blot technique. Gastrin mRNA was suppressed after cisplatin treatment both in vitro and in vivo. In vitro calcium but not vitamin D additions partially prevented the gastrin mRNA. In vivo, however, vitamin D and calcium were equally effective in preventing gastrin mRNA loss. PMID:18475933

  19. CCK2 receptor antagonists: pharmacological tools to study the gastrin-ECL cell-parietal cell axis.

    PubMed

    Håkanson, R; Ding, X Q; Norlén, P; Lindström, E

    1999-03-17

    Gastrin-recognizing CCK2 receptors are expressed in parietal cells and in so-called ECL cells in the acid-producing part of the stomach. ECL cells are endocrine/paracrine cells that produce and store histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. The ECL cells are the principal cellular transducer of the gastrin-acid signal. Activation of the CCK2 receptor results in mobilization of histamine (and pancreastatin) from the ECL cells with consequent activation of the parietal cell histamine H2 receptor. Thus, release of ECL-cell histamine is a key event in the process of gastrin-stimulated acid secretion. The oxyntic mucosal histidine decarboxylase (HDC) activity and the serum pancreastatin concentration are useful markers for the activity of the gastrin-ECL cell axis. Powerful and selective CCK2 receptor antagonits have been developed from a series of benzodiazepine compounds. These agents are useful tools to study how gastrin controls the ECL cells. Conversely, the close control of ECL cells by gastrin makes the gastrin-ECL cell axis well suited for evaluating the antagonistic potential of CCK2 receptor antagonists with the ECL-cell HDC activity as a notably sensitive and reliable parameter. The CCK2 receptor antagonists YF476, YM022, RP73870, JB93182 and AG041R were found to cause prompt inhibition of ECL-cell histamine and pancreastatin secretion and synthesis. The circulating pancreastatin concentration is raised, was lowered when the action of gastrin on the ECL cells was blocked by the CCK2 receptor antagonists. These effects were associated with inhibition of gastrin-stimulated acid secretion. In addition, sustained receptor blockade was manifested in permanently decreased oxyntic mucosal HDC activity, histamine concentration and HDC mRNA and CGA mRNA concentrations. CCK2 receptor blockade also induced hypergastrinemia, which probably reflects the impaired gastric acid secretion (no acid feedback inhibition of gastrin release

  20. Gastrin treatment stimulates β-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats.

    PubMed

    Téllez, Noèlia; Joanny, Géraldine; Escoriza, Jéssica; Vilaseca, Marina; Montanya, Eduard

    2011-07-01

    β-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost β-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on β-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 ± 52 mg vs. 436 ± 51 mg/dl, P < 0.05), and increased β-cell mass (1.15 ± 0.15 mg)) compared with vehicle-treated rats (0.67 ± 0.15 mg, P < 0.05). Gastrin treatment induced β-cell regeneration by enhancing β-cell neogenesis (increased number of extraislet β-cells in Px+G: 0.42 ± 0.05 cells/mm(2) vs. Px+V: 0.27 ± 0.07 cells/mm(2), P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 ± 0.38% vs. Px+V: 0.23 ± 0.10%, P < 0.05) and replication (Px+G: 1.65 ± 0.26% vs. S+V: 0.64 ± 0.14%; P < 0.05). In addition, reduced β-cell apoptosis contributed to the increased β-cell mass in gastrin-treated rats (Px+G: 0.07 ± 0.02%, Px+V: 0.23 ± 0.05%; P < 0.05). Gastrin action on β-cell regeneration and survival increased β-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.

  1. Gastrin induces ductal cell dedifferentiation and β-cell neogenesis after 90% pancreatectomy.

    PubMed

    Téllez, Noèlia; Montanya, Eduard

    2014-10-01

    Induction of β-cell mass regeneration is a potentially curative treatment for diabetes. We have recently found that long-term gastrin treatment results in improved metabolic control and β-cell mass expansion in 95% pancreatectomised (Px) rats. In this study, we investigated the underlying mechanisms of gastrin-induced β-cell mass expansion after Px. After 90%-Px, rats were treated with gastrin (Px+G) or vehicle (Px+V), pancreatic remnants were harvested on days 1, 3, 5, 7, and 14 and used for gene expression, protein immunolocalisation and morphometric analyses. Gastrin- and vehicle-treated Px rats showed similar blood glucose levels throughout the study. Initially, after Px, focal areas of regeneration, showing mesenchymal cells surrounding ductal structures that expressed the cholecystokinin B receptor, were identified. These focal areas of regeneration were similar in size and cell composition in the Px+G and Px+V groups. However, in the Px+G group, the ductal structures showed lower levels of keratin 20 and β-catenin (indicative of duct dedifferentiation) and higher levels of expression of neurogenin 3 and NKX6-1 (indicative of endocrine progenitor phenotype), as compared with Px+V rats. In Px+G rats, β-cell mass and the number of scattered β-cells were significantly increased compared with Px+V rats, whereas β-cell replication and apoptosis were similar in the two groups. These results indicate that gastrin treatment-enhanced dedifferentiation and reprogramming of regenerative ductal cells in Px rats, increased β-cell neogenesis and fostered β-cell mass expansion.

  2. Gut hormone release after intestinal resection.

    PubMed Central

    Besterman, H S; Adrian, T E; Mallinson, C N; Christofides, N D; Sarson, D L; Pera, A; Lombardo, L; Modigliani, R; Bloom, S R

    1982-01-01

    To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection. PMID:7117905

  3. The homeoproteins MAB-18 and CEH-14 insulate the dauer collagen gene col-43 from activation by the adjacent promoter of the Spermatheca gene sth-1 in Caenorhabditis elegans.

    PubMed

    Bando, Tetsuya; Ikeda, Tatsuji; Kagawa, Hiroaki

    2005-04-22

    Genome searches in this study indicate that the nematode Caenorhabditis elegans genome has 2582 bidirectionally oriented genes that account for more than 25% of the total genes. We analyze the transcriptional repression system for one of these predicted bidirectional promoters, which controls the expression of the spermathecal gene sth-1 and collagen gene col-43. These two genes are separated by 1.3 kb and are transcribed bidirectionally. sth-1 is expressed in spermatheca after the L4 stage and col-43 is expressed in the hypodermal cells of the L2d dauer stage. The upstream regions required for the expression of sth-1 and col-43 shared an overlapped control sequence. Two homeoproteins, MAB-18 and CEH-14, were isolated by yeast one-hybrid screening as binding proteins of the overlapped region. MAB-18 bound to two homeodomain-binding sites and interacted with CEH-14 to repress col-43 expression in spermatheca. These results indicate that the two homeoproteins interact with each other to repress col-43 expression in sth-1-expressing tissues. This is the first report of bidirectional gene regulation analysis in the C.elegans genome.

  4. Molecular biology of the peptide hormone families.

    PubMed

    Pearson, R K; Anderson, B; Dixon, J E

    1993-12-01

    The application of recombinant molecular biology has lead to remarkable advances in our understanding of the basic mechanisms of cell function in general and of the polarized GI endocrine cell in particular. This article focuses on some of the advances made towards determining the contribution of peptide hormone gene regulation to the regulation of physiological events in the GI tract. Application of these techniques to other subcellular processes involved in peptide hormone physiology such as subcellular trafficing in the regulated secretory pathway and post-translational processing have been equally impressive. For example, many of the key enzymes in the peptide hormone processing cascade have been cloned and are being studied at a molecular level. We have focused this article on the SS and gastrin peptides because of their known physiologic importance and interactions, and the depth of analysis accomplished to date. Studies using SS and gastrin as models have established principals that cover the spectrum of luminal regulation of gene activity to the identification of a single amino acid residue responsible for cAMP induction of SS gene expression. Many genes in the GI endocrine system have been cloned and the article by Dr. Habener (elsewhere in this issue) discusses progress made in understanding the complex regulation of the glucagon gene. We anticipate similar advances in studies of cholecystokinin, secretin, motilin, VIP, pancreatic polypeptide, and neuropeptide Y, whose genes have been cloned and initially characterized. Finally, as outlined in this article, the mechanisms of regulation of a specific gene often differ between sites of expression, even within the GI tract. Direct studies of the subcellular mechanisms regulating gene expression and other processes in GI endocrine cells await novel methods to maintain and propagate these cells. These studies will almost certainly involve new and creative uses of recombinant molecular biology.

  5. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    PubMed

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels.

  6. Expression, purification and characterization of recombinant toxins consisting of truncated gastrin 17 and pseudomonas exotoxin.

    PubMed

    Feng, Xiao-Li; Liu, Xi-Lin; Lu, Shi-Ying; Ren, Hong-Lin; Li, Yan-Song; Hu, Pan; Wang, Quan; Tong, Weihua; Yan, Dong-Ming; Zhou, Yu; Zhang, Song; Jin, Wen; Liu, Zeng-Shan

    2015-01-01

    Gastric cancer is a major cause of mortality and morbidity around world. However the effectiveness of the current approaches to the diagnosis and treatment of gastric cancer is limited. Recombinant targeted toxins may represent a novel direction of cancer therapy. In this study, we aimed to explore whether recombinant toxins fused with the truncated forms of G17 could target to kill cancer cells by recognizing CCK2R. Four recombinant Pseudomonas toxins PE38 fused with the forward or reverse truncated forms of G17 (G14 and G13) were successfully constructed, expressed, and purified. Their characteristics were further analyzed by SDS-PAGE, western blot and indirect immunofluorescence assay. The cytotoxicity assay demonstrated that only reversely fused recombinant toxins rG14PE38 and rG13PE38 exhibited certain toxicity on several cancer cell lines, and a competition assay indicated that the binding of the reverse gastrin-endotoxin to CCK2R (+) cells may be mediated by interaction between gastrin/gastrin-like and CCK2R.

  7. Carbamoylcholine and gastrin induce inositol lipid turnover in canine gastric parietal cells

    SciTech Connect

    Chiba, T.; Fisher, S.K.; Park, J.; Seguin, E.B.; Agranoff, B.W.; Yamada, Tadataka )

    1988-07-01

    The potential role of inositol phospholipid turnover in mediating acid secretion was examined in a preparation enriched for isolated canine gastric parietal cells. The stimulatory effects of carbamoylcholine (carbachol) and gastrin on parietal cell uptake of ({sup 14}C)aminopyrine were linked to dose- and time-dependent selective reduction in cellular phosphatidylinositol content, although the specific fatty acid composition of the phosphoinositides was not altered. Analysis of ({sup 3}H)inositol phosphates accumulated in cells prelabeled with ({sup 3}H)inositol revealed an increase in labeled inositol trisphosphate by 5 min of incubation with either carbachol or gastrin. Furthermore, after preincubation of parietal cells in medium containing ({sup 32}P)orthophosphate, the two secretagogues elicited a time-dependent decrease in {sup 32}P labeling of phosphatidylinositol 4,5-bisphosphate and concomitant increase in labeling of phosphatidic acid. These data demonstrate that the acid secretagogue actions of carbachol and gastrin are correlated with turnover of cellular inositol phospholipids in a preparation consisting predominantly of parietal cells.

  8. Isolation from beer and structural determination of a potent stimulant of gastrin release.

    PubMed

    Yokoo, Y; Kohda, H; Kusumoto, A; Naoki, H; Matsumoto, N; Amachi, T; Suwa, Y; Fukazawa, H; Ishida, H; Tsuji, K; Nukaya, H

    1999-01-01

    Beer was subjected to five successive chromatographic procedures to isolate the gastrin release-inducing activity, guided by bioassay of the fractions in anaesthetized Donryu rats. The procedures were: (1) hydrophobic interaction chromatography (aqueous effluent with an HP20 column); (2) weak cation-exchange chromatography (1 M acetic acid eluate with a CM Sephadex C-25 column); (3) gel filtration (methanol eluate with a Sephadex LH-20 column); (4) same as (2); (5) high-performance liquid chromatography (YMC-Pack ODS-AM with 7% acetonitrile-0.01 M HCl). The active component finally isolated had a specific activity approximately 10000 times higher than that of beer. It was identified by means of mass, 1H- and 13C-nuclear magnetic resonance spectral analyses as N-methyltyramine (NMT). The dose of NMT giving maximal gastrin-releasing activity was 25 microg/kg, and the 50% effective dose was approximately 10 microg/kg on oral administration to rats. NMT was isolated and identified as a gastrin release inducer in beer. Its concentration in beer is sufficient to account for most of the activity of beer.

  9. p-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways.

    PubMed

    Huynh, Nhi; Yim, Mildred; Chernoff, Jonathan; Shulkes, Arthur; Baldwin, Graham S; He, Hong

    2013-03-15

    Gastrins, including amidated (Gamide) and glycine-extended (Ggly) forms, function as growth factors for the gastrointestinal mucosa. The p-21-activated kinase 1 (PAK1) plays important roles in growth factor signaling networks that control cell motility, proliferation, differentiation, and transformation. PAK1, activated by both Gamide and Ggly, mediates gastrin-stimulated proliferation and migration, and activation of β-catenin, in gastric epithelial cells. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of proliferation in the normal colorectal mucosa in vivo. Mucosal proliferation was measured in PAK1 knockout (PAK1 KO) mice by immunohistochemistry. The expression of phosphorylated and unphosphorylated forms of the signaling molecules PAK1, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT), and the expression of β-catenin and its downstream targets c-Myc and cyclin D1, were measured in gastrin knockout (Gas KO) and PAK1 KO mice by Western blotting. The expression and activation of PAK1 are decreased in Gas KO mice, and these decreases are associated with reduced activation of ERK, AKT, and β-catenin. Proliferation in the colorectal mucosa of PAK1 KO mice is reduced, and the reduction is associated with reduced activation of ERK, AKT, and β-catenin. In compensation, antral gastrin mRNA and serum gastrin concentrations are increased in PAK1 KO mice. These results indicate that PAK1 mediates the stimulation of colorectal proliferation by gastrins via multiple signaling pathways involving activation of ERK, AKT, and β-catenin.

  10. The role of endogenous gastrin in the development of enterochromaffin-like cell carcinoid tumors in Mastomys natalensis: a study with the specific gastrin receptor antagonist AG-041R.

    PubMed Central

    Chiba, T.; Kinoshita, Y.; Sawada, M.; Kishi, K.; Baba, A.; Hoshino, E.

    1998-01-01

    We examined the effects of a newly synthesized gastrin receptor antagonist, AG-041R, on the growth of enterochromaffin-like (ECL) carcinoid tumors in Mastomys natalensis both in vitro and in vivo. AG-041R was as potent as the well known gastrin antagonist L365,260 in inhibiting not only the gastrin-induced release of histamine from but also histidine decarboxylase (HDC) gene expression in the ECL carcinoid tumor cells. AG-041R also inhibited gastrin-induced DNA synthesis and c-fos gene expression in the tumor cells. Furthermore, AG-041R significantly inhibited the growth of the transplanted Mastomys ECL carcinoid tumors in vivo. From these data, it is concluded that endogenous gastrin is involved in the growth of ECL carcinoid tumors in Mastomys natalensis. Moreover, AG-041R is shown to have a potential as an anti-neoplastic agent for ECL carcinoid tumor of the stomach. Images Figure 1 Figure 5 Figure 6 PMID:10461356

  11. CCK receptors-related signaling involved in nitric oxide production caused by gastrin 17 in porcine coronary endothelial cells.

    PubMed

    Grossini, Elena; Caimmi, Philippe; Molinari, Claudio; Uberti, Francesca; Mary, David; Vacca, Giovanni

    2012-03-05

    In anesthetized pigs gastrin-17 increased coronary blood flow through CCK1/CCK2 receptors and β(2)-adrenoceptors-related nitric oxide (NO) release. Since the intracellular pathway has not been investigated the purpose of this study was to examine in coronary endothelial cells the CCK1/CCK2 receptors-related signaling involved in the effects of gastrin-17 on NO release. Gastrin-17 caused a concentration-dependent increase of NO production (17.3-62.6%; p<0.05), which was augmented by CCK1/CCK2 receptors agonists (p<0.05). The effect of gastrin-17 was amplified by the adenylyl-cyclase activator and β(2)-adrenoceptors agonist (p<0.05), abolished by cAMP/PKA and β(2)-adrenoceptors and CCK1/CCK2 receptors blockers, and reduced by PLC/PKC inhibitor. Finally, Western-blot revealed the preferential involvement of PKA vs. PKC as downstream effectors of CCK1/CCK2 receptors activation leading to Akt, ERK, p38 and endothelial NOS (eNOS) phosphorylation. In conclusion, in coronary endothelial cells, gastrin-17 induced eNOS-dependent NO production through CCK1/CCK2 receptors- and β(2)-adrenoceptors-related pathway. The intracellular signaling involved a preferential PKA pathway over PKC.

  12. Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells.

    PubMed

    Liu, Tianbing; Konkalmatt, Prasad R; Yang, Yu; Jose, Pedro A

    2016-04-01

    The natriuretic effect of gastrin suggests a role in the coordinated regulation of sodium balance by the gastrointestinal tract and the kidney. The renal molecular targets and signal transduction pathways for such an effect of gastrin are largely unknown. Recently, we reported that gastrin induces NHE3 phosphorylation and internalization via phosphatidylinositol (PI) 3-kinase and PKCα. In this study, we show that gastrin induced the phosphorylation of human Na(+),K(+)-ATPase at serine 16, resulting in its endocytosis via Rab5 and Rab7 endosomes. The gastrin-stimulated phosphorylation of Na(+),K(+)-ATPase was dependent on PI 3-kinase because the phosphorylation was blocked by the PI 3-kinase inhibitor wortmannin. The phosphorylation of Na(+),K(+)-ATPase was also blocked by chelerythrine, a pan-PKC inhibitor, Gö-6976, a conventional PKC (cPKC) inhibitor, and BAPTA-AM, an intracellular calcium chelator, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The gastrin-mediated phosphorylation of Na(+),K(+)-ATPase was also inhibited by U-73122, a phospholipase C (PLC) inhibitor. These results suggest that gastrin regulates sodium hydrogen exchanger and pump in renal proximal tubule cells at the apical and basolateral membranes.

  13. Preclinical evaluation of 68Ga-DOTA-minigastrin for the detection of cholecystokinin-2/gastrin receptor-positive tumors.

    PubMed

    Brom, Maarten; Joosten, Lieke; Laverman, Peter; Oyen, Wim J G; Béhé, Martin; Gotthardt, Martin; Boerman, Otto C

    2011-04-01

    In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor-mediated uptake (p  =  .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.

  14. Hormone Therapy

    MedlinePlus

    ... estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  15. Spontaneous ECL cell carcinomas in cotton rats: natural course and prevention by a gastrin receptor antagonist.

    PubMed

    Martinsen, Tom C; Kawase, Shiro; Håkanson, Rolf; Torp, Sverre H; Fossmark, Reidar; Qvigstad, Gunnar; Sandvik, Arne K; Waldum, Helge L

    2003-12-01

    In our inbred strain of cotton rats (Sigmodon hispidus) 50% of the females develop spontaneous ECL cell-derived tumors in the acid-producing part of the stomach due to hypergastrinemia secondary to gastric hypoacidity. Although the mechanism behind the hypoacidity is unknown, the female cotton rat is an excellent model for studying ECL cell-related tumorigenesis. In this study we wanted to explore the malignancy potential of these tumors and the ability of a gastrin receptor antagonist (YF476) to prevent their development. First, nine hypergastrinemic female cotton rats (10 months of age) were diagnosed by laparotomy as having gastric tumors. They were killed 6 months later. Second, 18 female cotton rats (2 months of age) were dosed monthly for 6 months with YF476 (500 micro mol/kg body wt) by s.c. injection, while 21 age-matched animals received vehicle. Samples from each stomach were collected for histology, immunohistochemistry and northern blot analysis. The gastric tumors harbored cells with immunohistochemical features of ECL cells. The tumors were found at times to invade and penetrate the stomach wall and to metastasize to perigastric sites. ECL-derived tumor cells were discovered in peritoneal fluid. At death only 1 out of 18 animals given YF476 displayed carcinomas (invasive growth), compared with 7 out of 21 in the vehicle dosed control group (P = 0.048). The spontaneous gastric tumors in cotton rats derived from ECL cells. The tumors were able to penetrate the stomach wall and to metastasize by intracavital seeding. Gastrin receptor blockade lowered the incidence of such tumors. We propose that the tumors are ECL cell carcinomas and that gastrin is the driving force behind the transformation from normal to malignant ECL cells.

  16. Monitoring the impact of a mebendazole mass drug administration initiative for soil-transmitted helminthiasis (STH) control in the Western Visayas Region of the Philippines from 2007 through 2011.

    PubMed

    Sanza, Megan; Totanes, Francis Isidore; Chua, Paul Lester; Belizario, Vicente Y

    2013-08-01

    School-aged children in tropical developing countries carry the highest burden of soil-transmitted helminth (STH) infections in the world. The Western Visayas region of the Philippines continues to struggle with this as a major public health issue in both private and public schools. The War on Worms-Western Visayas approach was launched in 2007 with school-based mass drug administration (MDA) as one of the strategies to control morbidity from STH in support of the Department of Health - Integrated Helminth Control Program. This study aimed to determine trends in prevalence and intensity of STH infections as well as to assess related morbidity and program sustainability through 2011. A cross-sectional parasitologic survey was conducted on three independent samples of Grade 3 students in 2007, 2009, and 2011. Supporting aggregate data were obtained for MDA coverage, National Achievement Test mean percentage scores, and nutritional status. Tests for trend were utilized to detect changes in prevalence over time, with a particular emphasis on trends seen between 2009 and 2011. The initial impact of the program was robust as cumulative prevalence, infection intensities, and parasite densities were all reduced four years following the launch. However, subsequent and significant increases in each were found from 2009 until 2011. These results implicate issues with program sustainability, despite consistent MDA, and existing frameworks for environmental sanitation, hygiene, and education.

  17. Peptidyl hormones of endocrine cells origin in the gut--their discovery and physiological relevance.

    PubMed

    Ceranowicz, P; Warzecha, Z; Dembinski, A

    2015-02-01

    In 1902 William Bayliss and Ernest Starling discovered secretin and it was the beginning of general endocrinology as well as, endocrinology of gastrointestinal tract. Ernest Starling was also a first person who introduced a term hormone for the substances which serves to transfer the information between cells of organism. Subsequent years delivered discovery of successive hormones of the digestive tract. Gastrin was discovered in 1905; whereas cholecystokinin in 1928. Ghrelin and obestatin are last hormones determined in the gastrointestinal tract and they were found in 1999 and 2006, respectively. Both above hormones are originating from the common prohormone. In 60s of past century, the biochemical structure of the gastrointestinal tract hormones was determined for the first time. Substantial progress in endocrinology of the digestive tract took place when radioimmunoassay was employed to measure of hormones concentration. Subsequently, radiolabeled hormones were used to localize hormonal receptors. Next breakthrough in the gastrointestinal tract endocrinology happened after introduction to experimental methods the cloning of complementary DNA. This method has allowed, among the others, to establish the full structure of receptors as well as, a genes coding hormones and their receptors. Discovery of genes structure allowed subsequently introducing these genes into foreign cells, what gives a chance to obtain significant amount of recombined hormones possessing species specificity. This review is presenting a history of the gastrointestinal tract endocrinology, as well as a relevance of gastrointestinal tract hormones in the regulation of body physiological activity.

  18. Gastric acid secretion and gastrin production in the short bowel syndrome.

    PubMed Central

    Williams, N S; Evans, P; King, R F

    1985-01-01

    Excess gastric acid secretion and gastrin production may occur in patients with the short bowel syndrome but the two measurements have never been made simultaneously in man in response to a food stimulus. Using the technique of intragastric titration, this was carried out in eight patients after extensive small bowel resection resulting mainly from vascular occlusion and in eight matched normal control subjects. Basal acid output and peak acid output in response to pentagastrin was also measured separately. Although peak and integrated serum gastrin concentrations were significantly greater in patients (450 +/- SE 109 pg/ml; 113 +/- 2.9X10(-3) pg/ml/min) compared with control subjects (174 +/- 98 pg/ml; 6.1 +/- 2.0X10(-3) pg/ml/min p less than 0.05), no concomitant increase in acid secretion was shown either during intragastric titration or in response to pentagastrin. These findings indicate that there is no rationale for treating these patients with long term anti-ulcer therapy. PMID:4029719

  19. Fasting lowers gastrin-releasing peptide and FSH mRNA in the ovine anterior pituitary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

  20. Fasting lowers gastrin-releasing peptide and Fsh mRNA in the ovine anterior pituitary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

  1. Effect of somatostatin on the growth of gastrointestinal mucosa and pancreas in rats. Role of endogenous gastrin.

    PubMed Central

    Dembiński, A; Warzecha, Z; Konturek, S J; Schally, A V

    1987-01-01

    This study was undertaken to determine the influence of somatostatin on the growth of gastric, duodenal, and pancreatic tissue in rats placed on liquid diet. In the first part of the study animals were fed an elemental liquid diet for 10 days and then killed, and the growth of the oxyntic gland area of the stomach, 2 cm segments of duodenum and pancreatic tissue was determined. Feeding an elemental diet caused a decrease in organ weight, nucleic acid contents and serum gastrin level. Subsequent addition of pentagastrin prevented this reduction in organ weight and RNA and DNA contents while somatostatin failed to affect the decrease in growth parameters or serum gastrin level in tests with or without addition of pentagastrin. In a second part of the study, sham operated and antrectomised rats were used. Antrectomy caused a significant decrease in serum gastrin concentration and resulted in a significant reduction in the weight and RNA and DNA contents of the tissue tested. As in liquid diet, subsequent administration of pentagastrin prevented the reduction in the growth parameters both in tests with and without somatostatin. These results suggest that somatostatin inhibits the growth of the gastroduodenal mucosa by a mechanism involving, at least in part, the suppression of gastrin release. PMID:2446962

  2. Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion.

    PubMed

    Feng, Jianying; Petersen, Clark D; Coy, David H; Jiang, Jian-Kang; Thomas, Craig J; Pollak, Martin R; Wank, Stephen A

    2010-10-12

    The calcium-sensing receptor (CaR) is the major sensor and regulator of extracellular Ca(2+), whose activity is allosterically regulated by amino acids and pH. Recently, CaR has been identified in the stomach and intestinal tract, where it has been proposed to function in a non-Ca(2+) homeostatic capacity. Luminal nutrients, such as Ca(2+) and amino acids, have been recognized for decades as potent stimulants for gastrin and acid secretion, although the molecular basis for their recognition remains unknown. The expression of CaR on gastrin-secreting G cells in the stomach and their shared activation by Ca(2+), amino acids, and elevated pH suggest that CaR may function as the elusive physiologic sensor regulating gastrin and acid secretion. The genetic and pharmacologic studies presented here comparing CaR-null mice and wild-type littermates support this hypothesis. Gavage of Ca(2+), peptone, phenylalanine, Hepes buffer (pH 7.4), and CaR-specific calcimimetic, cinacalcet, stimulated gastrin and acid secretion, whereas the calcilytic, NPS 2143, inhibited secretion only in the wild-type mouse. Consistent with known growth and developmental functions of CaR, G-cell number was progressively reduced between 30 and 90 d of age by more than 65% in CaR-null mice. These studies of nutrient-regulated G-cell gastrin secretion and growth provide definitive evidence that CaR functions as a physiologically relevant multimodal sensor. Medicinals targeting diseases of Ca(2+) homeostasis should be reviewed for effects outside traditional Ca(2+)-regulating tissues in view of the broader distribution and function of CaR.

  3. Lansoprazole induces mucosal protection through gastrin receptor-dependent up-regulation of cyclooxygenase-2 in rats.

    PubMed

    Tsuji, Shingo; Sun, Wei-Hao; Tsujii, Masahiko; Kawai, Naoki; Kimura, Arata; Kakiuchi, Yoshimi; Yasumaru, Shoichi; Komori, Masato; Murata, Hiroaki; Sasaki, Yutaka; Kawano, Sunao; Hori, Masatsugu

    2002-12-01

    Proton pump inhibitors (PPIs) are antiulcer agents that have both gastric antisecretory and mucosal protective actions. The mechanisms of PPI-induced gastric mucosal protection are not known. The present study was designed to examine the mechanism for lansoprazole-induced gastric mucosal protection in rats. Rats were given 0.5, 5, and 50 mg/kg/day lansoprazole alone or both lansoprazole (50 mg/kg/day) and a specific gastrin receptor antagonist 3R-1-(2,2-diethoxyethyl)-((4-methylphenyl)amino-carbonyl methyl)-3-((4-methylphenyl)ureidoindoline-2- one) (AG-041R) (3, 10, and 30 mg/kg/day) for 14 days. Serum gastrin concentrations were measured. The expression of cyclooxygenases (COX-1 and COX-2) in the gastric mucosa was analyzed using Western blotting and immunohistochemical staining. Another series of rats was used to examine the 1) levels of prostaglandin (PG) E2 in gastric mucosa, 2) influences of the drugs on gastric damage caused by absolute ethanol, and 3) effects of a COX-2-specific inhibitor on PGE2 in the gastric mucosa and the mucosal protection afforded by lansoprazole. Lansoprazole dose dependently increased the serum gastrin concentration and enhanced the mucosal expression of COX-2 but not that of COX-1. Lansoprazole increased gastric mucosal PGE2 and reduced gastric damage caused by ethanol. Concomitant administration of AG-041R abolished the lansoprazole-induced COX-2 expression, and increased mucosal PGE2 and mucosal protection. A specific COX-2 inhibitor blocked the lansoprazole-induced increase in mucosal PGE2 and mucosal protection. Activation of gastrin receptors by endogenous gastrin has a pivotal role in the effects of lansoprazole on COX-2 up-regulation and mucosal protection in the rat stomach.

  4. PAK1 interacts with beta-catenin and is required for the regulation of the beta-catenin signalling pathway by gastrins.

    PubMed

    He, Hong; Shulkes, Arthur; Baldwin, Graham S

    2008-10-01

    Beta-catenin regulates cell-cell adhesion by binding to E-cadherin at the cell membrane and, when translocated into the nucleus, mediates signalling by activation of transcription factors such as TCF4. Mutations of the components of the Wnt/beta-catenin pathway are found in many gastrointestinal cancers. Gastrins, including amidated (Gamide) and glycine-extended (Ggly) gastrin(17), stimulate the proliferation of gastrointestinal cancer cells. Gastrins also regulate beta-catenin signalling through multiple pathways which seem to converge on p21-activated kinase 1 (PAK1). In this study, we have investigated the role of PAK1 in the regulation of beta-catenin signalling by gastrins. Here we report for the first time that PAK1 associated with beta-catenin. Both Gamide and Ggly stimulated the phosphorylation and activation of beta-catenin in a PAK1-dependent manner. A kinase-inactive mutant PAK1(K299A) blocked the gastrin-stimulated dissociation of beta-catenin from E-cadherin, translocation of beta-catenin from the cell membrane to the nucleus, and association of beta-catenin with the transcription factor TCF4. The PAK1(K299A) mutant also inhibited the stimulation of the expression of c-myc and cyclin D1, and of cell proliferation and migration, by gastrins. The results indicate that gastrins regulate beta-catenin signalling through a PAK1-dependent pathway. PAK1 seems to be the point of convergence of multiple signalling pathways activated by gastrins.

  5. Evaluation of three novel cholecystokinin-B/gastrin receptor antagonists: a study of their effects on rat stomach enterochromaffin-like cell activity.

    PubMed

    Ding, X Q; Lindström, E; Håkanson, R

    1997-11-01

    Gastrin stimulates rat stomach enterochromaffin-like (ECL) cells via activation of cholecystokinin-B/gastrin receptors. The stimulation is manifested in the activation of the histamine-forming enzyme histidine decarboxylase and in the secretion of histamine and pancreastatin, a chromogranin A-derived peptide. We have examined the short-term effects of three novel cholecystokinin-B/gastrin receptor antagonists (YF476, JB93182 and AG041R) on the ECL cells in intact fasted rats. The drugs and/or gastrin were infused intravenously for 3 hr and the oxyntic mucosal histidine decarboxylase activity and the serum pancreastatin concentration were measured. We also studied the effects of the three drugs on gastric emptying in mice, a cholecystokinin-A receptor-mediated response. YF476, JB93182 and AG041R antagonized the gastrin-evoked histidine decarboxylase activation in a dose-dependent manner. YF476, JB93182 and AG041R induced maximal inhibition at 0.03, 0.1 and 0.1 mumol kg-1 hr-1, respectively; the corresponding ID50 values were 0.002, 0.008, and 0.01 mumol kg-1 hr-1. YF476 was selected for further analysis. It produced a rightward shift of the gastrin dose-response curve, consistent with competitive inhibition. Moreover, it antagonized the omeprazole-evoked histidine decarboxylase activation and the gastrin- and omeprazole-induced rise in the circulating pancreastatin concentration. None of the three drugs tested inhibited gastric emptying or prevented the cholecystokinin-8s-induced inhibition of gastric emptying at the doses tested. The results show that YF476, JB93182 and AG041R are potent and selective cholecystokinin-B/ gastrin receptor antagonists, and that YF476 is 4-5 times more potent than JB93182 and AG041R.

  6. Hormonal responses to complete or hydrolyzed protein diets in patients after upper gastrointestinal surgery.

    PubMed

    Simko, V; Chen, M H

    1986-01-01

    Six gastrointestinal hormones were measured in the plasma of six healthy controls and long-term changes were evaluated in six patients 2-20 years after upper gastrointestinal surgery. In a metabolic unit study we determined fasting hormonal levels, the time to peak hormonal response, and a 135-minute hormonal response to the meal. Test meals were isocaloric, 500 kcal, and isonitrogenous, consisting either of natural breakfast components or of complete liquid diets with intact protein (Ensure) or hydrolyzed protein (Vital). Postsurgical subjects were in good health and had no postcibal complaints. Nevertheless, their hemoglobin and serum albumin were significantly lower than in controls. Postsurgical subjects had higher fasting gastrin (121.3 +/- 11.6 vs 65.4 +/- 6.6 pg/ml, P less than .01) and motilin (148.7 +/- 32.9 vs 70.4 +/- 13.1 pg/ml, P less than .05) than controls. In postsurgical patients the peak gastrin and pancreatic glucagon responses to meals were obtained in significantly shorter time. Their total response to motilin and secretin to meals was significantly lower than in controls. Fasting glucose and the meal-induced responses of insulin and vasoactive intestinal polypeptide were not different from controls. The nature of dietary protein did not significantly affect hormonal responses to feeding. We conclude that gastrointestinal hormonal changes persist many years after surgery. These changes are probably related to faster transit of meals with a generally weaker total hormonal response to feeding. Although these differences from normal may be nutritionally well compensated, they may become important in periods of metabolic stress.

  7. Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide.

    PubMed

    Zhang, Wei; Garg, Sanjay; Eldi, Preethi; Zhou, Fiona Huan-Huan; Johnson, Ian R D; Brooks, Doug A; Lam, Frankie; Rychkov, Grigori; Hayball, John; Albrecht, Hugo

    2016-11-20

    In recent years G protein-coupled receptors (GPCRs) have emerged as crucial tumorigenic factors that drive aberrant cancer growth, metastasis and angiogenesis. Consequently, a number of GPCRs are strongly expressed in cancer derived cell lines and tissue samples. Therefore a rational anti-cancer strategy is the design of nano-medicines that specifically target GPCRs to bind and internalise cytotoxic drugs into cancer cells. Herein, we report the genetic engineering of a self-assembling nanoparticle based on elastin-like polypeptide (ELP), which has been fused with gastrin releasing peptide (GRP). These nanoparticles increased intracellular calcium concentrations when added to GRP receptor positive PC-3 prostate cancer cells, demonstrating specific receptor activation. Moreover, GRP-displaying fluorescent labelled nanoparticles showed specific cell-surface interaction with PC-3 prostate cancer cells and increased endocytic uptake. These nanoparticles therefore provide a targeted molecular carrier system for evaluating the delivery of cytotoxic drugs into cancer cells.

  8. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    NASA Astrophysics Data System (ADS)

    Brillouet, S.; Caselles, O.; Dierickx, L. O.; Mestre, B.; Nalis, J.; Picard, C.; Favre, G.; Poirot, M.; Silvente-Poirot, S.; Courbon, F.

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and " in silico" drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ( 111In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with 111In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  9. Spinal cord interneurons expressing the gastrin releasing peptide receptor convey itch through VGLUT2-mediated signaling.

    PubMed

    Aresh, Bejan; Freitag, Fabio B; Perry, Sharn; Blümel, Edda; Lau, Joey; Franck, Marina C M; Lagerström, Malin C

    2017-02-01

    Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. In the spinal cord, neurons expressing the gastrin releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR-population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominantly excitatory interneurons that are found in the dorsal lamina, especially in lamina II-IV. Application of the specific agonist gastrin releasing peptide (GRP) induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox;Grpr-Cre mice) displayed less spontaneous itch, and attenuated responses to both histaminergic and non-histaminergic agents. We could also show that application of the itch-inducing peptide natriuretic polypeptide b (NPPB) induces calcium influx in a sub-population of Grpr-Cre neurons. To summarize, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  10. Mercuric chloride-induced gastrin/cholecystokinin 8 immunoreactivity in the central nervous system of the terrestrial slug Semperula maculata: an immunohistochemical study.

    PubMed

    Londhe, Sunil; Kamble, Nitin

    2013-12-01

    We measured the immunoreactivity of the neuropeptide gastrin cholecystokinin 8 (gastrin/CCK 8) in neurons of the terrestrial slug Semperula maculata following acute treatment with mercuric chloride (HgCl2). The distribution of gastrin/CCK 8 was analyzed in neurons of different regions, specifically from cerebral ganglia (procerebrum (pro-c), mesocerebrum (meso-c) and metacerebrum (meta-c). In the control group, neurons of pedal, pleural, parietal and visceral ganglia showed positive immunoreactivity using vertebrate antiserum against gastrin/CCK 8. Gastrin/CCK 8 immunoreactivity was also seen in the fibers and neuropil region of all ganglia. In the cerebral ganglion, 10, 12 and 8 % of the neurons from pro-c, meso-c and meta-c, respectively, were stained with the antibody. The immunostaining was increased in neurons (giant, large, medium and small) after HgCl2 treatment. The treatment greatly increased the mucin content within the neurons. Exposure to HgCl2 enhanced gastrin immunoreactivity in the neurons and this increased with time. Results are discussed in the context of neuropathology in cerebral ganglia associated with the feeding behavior of Semperula maculata.

  11. [Serological tests of functional activity of the digestive system (gastrin, pepsinogen-I, trypsin), general IgE and serum cortisol levels in children with hepatitis A and B].

    PubMed

    Kalagina, L S; Pavlov, Ch S; Fomin, Iu A

    2013-01-01

    The mild form of hepatitis A and B with children is attended by a functional activity of pancreatic gland (tripsin), mucous coats of stomach and duodenum (gastrin) which permits to consider them as a factor of the risk of digestive organs combined pathology starting with the disease acuity. Differences in gastrin levels with children depending on hepatitis etiology were specified. Highest levels of gastrin were observed with persons suffering from hepatitis B.

  12. The Role of H. pylori CagA in Regulating Hormones of Functional Dyspepsia Patients

    PubMed Central

    Meng, Wang-Ping; Wang, Zhong-Qiong; Deng, Jia-Qi; Liu, Yi

    2016-01-01

    Helicobacter pylori (H. pylori, Hp) colonizes the stomachs of approximately 20%–80% of humans throughout the world. The Word Healthy Organization (WHO) classified H. pylori as a group 1 carcinogenic factor in 1994. Recently, an increasing number of studies has shown an association between H. pylori infection and various extragastric diseases. Functional dyspepsia (FD) is considered a biopsychosocial disorder with multifactorial pathogenesis, and studies have shown that infection with CagA-positive H. pylori strains could explain some of the symptoms of functional dyspepsia. Moreover, CagA-positive H. pylori strains have been shown to affect the secretion of several hormones, including 5-HT, ghrelin, dopamine, and gastrin, and altered levels of these hormones might be the cause of the psychological disorders of functional dyspepsia patients. This review describes the mutual effects of H. pylori and hormones in functional dyspepsia and provides new insight into the pathogenesis of functional dyspepsia. PMID:27840636

  13. Synthesis of analogues of the Des-Phe-NH2 C-terminal hexapeptide of cholecystokinin showing gastrin antagonist activity.

    PubMed

    Laur, J; Rodriguez, M; Aumelas, A; Bali, J P; Martinez, J

    1986-04-01

    Four analogues of Z-CCK-27-32-NH2, Z-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2, a cholecystokinin receptor antagonist have been synthesized by solution methodology. In these analogues, Z-Tyr(SO3-)-Nle-Gly-Trp-Met-Asp-NH2 16, Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-NH2 17, BOC-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2 24 and Boc-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp-NH2 25 methionyl residues were replaced by norleucyl residues. Preliminary biological activity on gastrin-induced acid secretion, in rat, are reported. These derivatives proved to antagonize the action of gastrin, with ED 50 of between 0.5 and 3 mg/kg.

  14. Effect of netazepide, a gastrin/CCK2 receptor antagonist, on gastric acid secretion and rabeprazoleinduced hypergastrinaemia in healthy subjects

    PubMed Central

    Boyce, Malcolm; Dowen, Sally; Turnbull, Gillian; van den Berg, Frans; Zhao, Chun-Mei; Chen, Duan; Black, James

    2015-01-01

    Aims To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. Methods Thirty healthy subjects completed a double-blind, randomized, parallel group trial of oral netazepide and rabeprazole, alone and combined, once daily for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and end of treatment, gastric biopsies at baseline and end of treatment and basal and pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment withdrawal. Results All treatments similarly inhibited pentagastrin-stimulated gastric acid secretion. All treatments increased serum gastrin, but the combination and rabeprazole did so more than netazepide alone. The combination also reduced basal acid secretion. Rabeprazole increased plasma CgA, whereas netazepide and the combination reduced it. None of the biopsies showed enterochromaffin-like (ECL) cell hyperplasia. Withdrawal of treatments led neither to rebound hyperacidity nor dyspepsia. Conclusions Netazepide suppressed pentagastrin-stimulated gastric acid secretion as effectively as did rabeprazole. The reduction in basal acid secretion and greater increase in serum gastrin by the combination is consistent with more effective acid suppression. Despite our failure to show rabeprazole-induced ECL cell hyperplasia and rebound hyperacidity, the increase in plasma CgA after rabeprazole is consistent with a trophic effect on ECL cells, which netazepide prevented. Thus, netazepide is a potential treatment for the trophic effects of hypergastrinaemia and, with or without a PPI, is a potential treatment for acid-related conditions. PMID:25335860

  15. Efficient asymmetric synthesis of novel gastrin receptor antagonist AG-041R via highly stereoselective alkylation of oxindole enolates.

    PubMed

    Emura, Takashi; Esaki, Toru; Tachibana, Kazutaka; Shimizu, Makoto

    2006-10-27

    An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.

  16. Gastrin stimulates a cholecystokinin-2-receptor-expressing cardia progenitor cell and promotes progression of Barrett's-like esophagus

    PubMed Central

    Hayakawa, Yoku; Wang, Hongshan; Au, Andrew S.; Luna, Aesis M.; Chang, Wenju; Jin, Guangchun; Bhagat, Govind; Abrams, Julian A.; Friedman, Richard A.; Varro, Andrea; Wang, Kenneth K.; Boyce, Malcolm; Rustgi, Anil K.; Sepulveda, Antonia R.; Quante, Michael; Wang, Timothy C.

    2017-01-01

    Objective The incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression of its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use of proton pump inhibitors (PPIs), has been suggested as one possible risk factor. The gastrin receptor, CCK2R, is expressed in the cardia and upregulated in BE, suggesting the involvement of the gastrin-CCK2R pathway in progression. In the L2-IL-1β mouse model, Barrett's-like esophagus arises from the gastric cardia. Therefore, we aimed to analyze the effect of hypergastrinemia on CCK2R+ progenitor cells in L2-IL-1β mice. Design L2-IL-1β mice were mated with hypergastrinemic (INS-GAS) mice or treated with PPIs to examine the effect of hypergastrinemia in BE progression. CCK2R-CreERT crossed with L2-IL-1β mice were used to analyze the lineage progenitor potential of CCK2R+ cells. Cardia glands were cultured in vitro, and the effect of gastrin treatment analyzed. L2-IL-1β mice were treated with a CCK2R antagonist YF476 as a potential chemopreventive drug. Results Hypergastrinemia resulted in increased proliferation and expansion of Barrett's-like esophagus. Lineage tracing experiments revealed that CCK2R+ cells are long-lived progenitors that can give rise to such lesions under chronic inflammation. Gastrin stimulated organoid growth in cardia culture, while CCK2R inhibition prevented Barrett's-like esophagus and dysplasia. Conclusions Our data suggest a progression model for BE to EAC in which CCK2R+ progenitor cells, stimulated by hypergastrinemia, proliferate to give rise to metaplasia and dysplasia. Hypergastrinemia can result from PPI use, and the effects of hypergastrinemia in human BE should be studied further. PMID:27448962

  17. Synthesis and biological activity of partially modified retro-inverso pseudopeptide derivatives of the C-terminal tetrapeptide of gastrin.

    PubMed

    Rodriguez, M; Dubreuil, P; Bali, J P; Martinez, J

    1987-05-01

    The effects of partial retro-inverso modifications of selected peptide bonds of the N-terminal tetrapeptide of gastrin have been studied. In some of the synthesized compounds, the phenylalanyl residue has been replaced by the (R,S)-2-benzylmalonyl, 3-phenylpropionyl, benzylcarbamoyl, or benzyloxycarbonyl moieties. All pseudopeptides showed affinity for the gastrin receptor, in vitro, with potencies varying from IC50 = 10(-7) to IC50 = 10(-4) M. These compounds exhibited little or no activity on acid secretion in the anesthetized rat but were able to antagonize the action of gastrin. Among the most potent were Boc-Trp-Leu-gAsp-CO-CH2CH2C6H5 (20) (ED50 = 0.15 microM/kg), Boc-Trp-Leu-gAsp-m(R,S)Phe-NH2 (3) (ED50 = 0.15 microM/kg), and Boc-Trp-gLeu-D-Asp-m(R,S)Phe-NH2 (7) (ED50 = 0.3 microM/kg).

  18. CEA Level, Radical Surgery, CD56 and CgA Expression Are Prognostic Factors for Patients With Locoregional Gastrin-Independent GNET.

    PubMed

    Li, Yuan; Bi, Xinyu; Zhao, Jianjun; Huang, Zhen; Zhou, Jianguo; Li, Zhiyu; Zhang, Yefan; Li, Muxing; Chen, Xiao; Hu, Xuhui; Chi, Yihebali; Zhao, Dongbing; Zhao, Hong; Cai, Jianqiang

    2016-05-01

    Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs.All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed.Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0-38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors.Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs.

  19. Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients.

    PubMed

    Sonne, David P; Hare, Kristine J; Martens, Pernille; Rehfeld, Jens F; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K

    2013-02-15

    Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.

  20. Gastrointestinal hormone mRNA expression in human colonic adenocarcinomas, hepatic metastases and cell lines

    PubMed Central

    Monges, G; Biagini, P; Cantaloube, J F; De Micco, P; Parriaux, D; Seitz, J F; Delpero, J R; Hassoun, J

    1996-01-01

    Aims—(1) To investigate the expression of the four main hormones of the digestive tract by performing reverse transcription polymerase chain reaction (RT-PCR) on a series of samples, comprising tumoral and healthy colonic tissues, hepatic metastases and colonic cell line samples; and (2) to study the patterns of labelling obtained with serological and morphological markers. Methods—After extraction and reverse transcription, gastrin, somatostatin, cholecystokinin (CCK) and transforming growth factor α (TGFα) mRNAs were detected by PCR and nested PCR using specific primers. The corresponding proteins were detected by immunohistochemistry. Results—The cell lines expressed all four mRNAs. Gastrin mRNA was present in most tumoral and metastatic samples, while the somatostatin transcript was detected in all samples and was frequently overexpressed in the normal colon. TGFα mRNA was expressed systematically in tumours of the right and transverse colon, but not in those located in the left colon; the expression of CCK mRNA was systematically absent in the left colon. Conclusions—The data presented here shed some light on the transcriptional events involved in the production of the various hormones present in the gastrointestinal tract, in both healthy and tumoral tissues. The various mRNAs expressed in cell lines are therefore not systematically expressed in the human pathology. Images PMID:16696065

  1. Gastrin-releasing peptide blockade as a broad-spectrum anti-inflammatory therapy for asthma

    PubMed Central

    Zhou, Shutang; Potts, Erin N.; Cuttitta, Frank; Foster, W. Michael; Sunday, Mary E.

    2011-01-01

    Gastrin-releasing peptide (GRP) is synthesized by pulmonary neuroendocrine cells in inflammatory lung diseases, such as bronchopulmonary dysplasia (BPD). Many BPD infants develop asthma, a serious disorder of intermittent airway obstruction. Despite extensive research, early mechanisms of asthma remain controversial. The incidence of asthma is growing, now affecting >300 million people worldwide. To test the hypothesis that GRP mediates asthma, we used two murine models: ozone exposure for air pollution-induced airway hyperreactivity (AHR), and ovalbumin (OVA)-induced allergic airway disease. BALB/c mice were given small molecule GRP blocking agent 77427, or GRP blocking antibody 2A11, before exposure to ozone or OVA challenge. In both models, GRP blockade abrogated AHR and bronchoalveolar lavage (BAL) macrophages and granulocytes, and decreased BAL cytokines implicated in asthma, including those typically derived from Th1 (e.g., IL-2, TNFα), Th2 (e.g., IL-5, IL-13), Th17 (IL-17), macrophages (e.g., MCP-1, IL-1), and neutrophils (KC = IL-8). Dexamethasone generally had smaller effects on all parameters. Macrophages, T cells, and neutrophils express GRP receptor (GRPR). GRP blockade diminished serine phosphorylation of GRPR with ozone or OVA. Thus, GRP mediates AHR and airway inflammation in mice, suggesting that GRP blockade is promising as a broad-spectrum therapeutic approach to treat and/or prevent asthma in humans. PMID:21252304

  2. Obese and lean Zucker rats respond similarly to intraperitoneal administration of gastrin-releasing peptides.

    PubMed

    Washington, Martha C; Park, Karen H; Sayegh, Ayman I

    2014-08-01

    The Zucker rat is an animal model used to study obesity and the control of food intake by various satiety peptides. The amphibian peptide bombesin (Bn) reduces cumulative food intake similarly in both obese and lean weanling Zucker rats. Here, we hypothesized that intraperitoneal (i.p) administration of gastrin-releasing peptides-10, -27 and -29 (GRP-10, GRP-27, GRP-29), which are the mammalian forms of Bn, would reduce first meal size (MS, 10% sucrose) and prolong the intermeal interval (IMI, time between first and second meals) similarly in obese and lean adult Zucker rats. To test this hypothesis, we administered GRP-10, GRP-27 and GRP-29 (0, 2.1, 4.1 and 10.3 nmol/kg) i.p. to obese and lean male Zucker rats (who were deprived of overnight food but not water) and then measured the first and second MS, IMI and satiety ratio (SR, IMI/MS). We found that in both obese and lean rats, all forms of GRP reduced the first MS, and in lean rats, they also decreased the second MS. Additionally, GRP-10 and GRP-29 prolonged the IMI in both obese and lean rats, but GRP-27 only prolonged it in lean rats. Finally, we found that all forms of GRP increased the SR in both obese and lean rats. In agreement with our hypothesis, we conclude that all forms of GRP reduce food intake in obese and lean adult Zucker rats similar to Bn in weanling rats.

  3. Oxygen, gastrin-releasing Peptide, and pediatric lung disease: life in the balance.

    PubMed

    Sunday, Mary E

    2014-01-01

    Excessive oxygen (O2) can cause tissue injury, scarring, aging, and even death. Our laboratory is studying O2-sensing pulmonary neuroendocrine cells (PNECs) and the PNEC-derived product gastrin-releasing peptide (GRP). Reactive oxygen species (ROS) generated from exposure to hyperoxia, ozone, or ionizing radiation (RT) can induce PNEC degranulation and GRP secretion. PNEC degranulation is also induced by hypoxia, and effects of hypoxia are mediated by free radicals. We have determined that excessive GRP leads to lung injury with acute and chronic inflammation, leading to pulmonary fibrosis (PF), triggered via ROS exposure or by directly treating mice with exogenous GRP. In animal models, GRP-blockade abrogates lung injury, inflammation, and fibrosis. The optimal time frame for GRP-blockade and the key target cell types remain to be determined. The concept of GRP as a mediator of ROS-induced tissue damage represents a paradigm shift about how O2 can cause injury, inflammation, and fibrosis. The host PNEC response in vivo may depend on individual ROS sensing mechanisms and subsequent GRP secretion. Ongoing scientific and clinical investigations promise to further clarify the molecular pathways and clinical relevance of GRP in the pathogenesis of diverse pediatric lung diseases.

  4. The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis: A Meta-Analysis.

    PubMed

    Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

    2016-05-01

    A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG).An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs).Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45-0.51) and 0.79 (95% CI: 0.77-0.81), respectively. The DOR was 5.93 (95% CI: 2.93-11.99), and the AUC was 0.82.G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future.

  5. AG-041R, a gastrin/CCK-B antagonist, stimulates chondrocyte proliferation and metabolism in vitro.

    PubMed

    Ochi, M; Kawasaki, K; Kataoka, H; Uchio, Y; Nishi, H

    2001-05-25

    A newly synthesized compound, AG-041R, 3R-1-(2,2Diethoxyethyl)-3-((4methylphenyl) amino-carbonylmethyl)-3-((4methylphenyl)ureido-indoline-2-one), is a cholecyctokinin-B/gastrin receptor antagonist, but unexpectedly magnified cartilage formation in vivo. Indeed, AG-041R is a potentially effective reagent for the repair of articular cartilage defects. To clarify its effects on chondrocytes, we studied the proliferation, matrix formation, and gene expression of rabbit primary chondrocytes cultured in type I collagen gel composites with AG-041R. Both proliferation and glycosaminoglycan synthesis were stimulated with 1 microM AG-041R, but suppressed with 10 microM. The ratio of the amounts of two chondroitin sulfate isomers, chondroitin-6-sulfate to chondroitin-4-sulfate (an indicator of cartilage maturation), increased with 1 microM but decreased with 10 microM AG-041R. Gene expression analysis showed there was no change in the relative expression levels of chondrocyte markers, Type II collagen and Aggrecan, and osteoblast and adipocyte markers, Type I collagen and PPARgamma, respectively. These findings suggest that adequate concentrations of AG-041R stimulate proliferation of chondrocytes in the matrix, without changing their differentiated characteristics.

  6. Gastrin Releasing Peptide Modulates Fast Delayed Rectifier Potassium Current in Per1-Expressing SCN Neurons

    PubMed Central

    Gamble, Karen L.; Kudo, Takashi; Colwell, Christopher S.; McMahon, Douglas G.

    2011-01-01

    The mammalian circadian clock in the suprachiasmatic nucleus (SCN) drives and maintains 24-h physiological rhythms, the phases of which are set by the local environmental light-dark cycle. Gastrin releasing peptide (GRP) communicates photic phase setting signals in the SCN by increasing neurophysiological activity of SCN neurons. Here, the ionic basis for persistent GRP-induced changes in neuronal activity was investigated in SCN slice cultures from Per1::GFP reporter mice during the early night. Recordings from Per1-fluorescent neurons in SCN slices several hours after GRP treatment revealed a significantly greater action potential frequency, a significant increase in voltage-activated outward current at depolarized potentials, and a significant increase in 4-aminopyridine (4-AP) sensitive fast delayed rectifier (fDR) potassium currents when compared to vehicle-treated slices. In addition, the persistent increase in spike rate following early night GRP application was blocked in SCN neurons from mice deficient in Kv3 channel proteins. Because fDR currents are regulated by the clock and are elevated in amplitude during the day, the present results support the model that GRP delays the phase of the clock during the early night by prolonging day-like membrane properties of SCN cells. Furthermore, these findings implicate fDR currents in the ionic basis for GRP-mediated entrainment of the primary mammalian circadian pacemaker. PMID:21454290

  7. [Serum gastrin: interests and limitations of radio-immunoassay (author's transl)].

    PubMed

    Rougier, P; Linhart, N; Bok, B

    1980-01-01

    Radio-immunoassay of serum gastrin may now be carried out in all laboratories of radio-immunology. Comparison of two commercial kits A: Schwartz-Mann and B: CEA-SORIN according to criteria of specificity, sensitivity and reproducibility within and between systems, shows that they both permit the detection of pathological hypergastrinemias (Zollinger Ellison and atropic gastritis). Both kits have an identical intra-system coefficient of variation (10 p. cent and 7 p. cent for A, 5 p. cent and 8 p. cent for B) on the other hand, the inter-system coefficient of variation is better for kit B (22,4 p. cent and 37 p. cent for kit A, and 11,5 p. cent and 14,2 p. cent for kit B). The normal values for each kit are quite different: 97 + 64 pg.ml-1 for A and 51 . 23 pg.ml-1 for B preventing one from comparing estimations carried out with two different kits.

  8. Hormone impostors

    SciTech Connect

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  9. Hormonal abnormalities of the pancreas and gut in cystic fibrosis.

    PubMed

    Adrian, T E; McKiernan, J; Johnstone, D I; Hiller, E J; Vyas, H; Sarson, D L; Bloom, S R

    1980-09-01

    We have investigated the effect of cystic fibrosis on alimentary hormones in 10 children by measuring the pancreatic and gut hormone rsponse to a milk drink. Plasma insulin and gastric inhibitory peptide were both significantly reduced (P < 0.05 and P < 0.005, respectively, at 15 min) in the patients with cystic fibrosis, compared with controls, even though the early glucose rise was greater in the former group (P < 0.05 at 15 min). Fasting levels of pancreatic polypeptide were significantly lower in the fibrocystic children (P < 0.01), and the normal response to milk was completely abolished in these patients (P < 0.001). Fasting plasma enteroglucagon concentrations were grossly abolished in the cystic fibrosis patients (P < 0.001) and these remained elevated throughout the test. No significant differences were seen in basal or postmilk responses of plasma glucagon, gastrin, secretin, vasoactive intestinal peptide, or motilin in cystic fibrosis. It would thus appear that the pancreatic polypeptide cell is more susceptible to the effects of the disease process than the beta or alpha cell in cystic fibrosis. Some aspects of the abnormalities in the gastrointestinal endocrine system were similar to those seen in celiac disease and tropical sprue and may, therefore, effect a similar hormonal response in these patients with cystic fibrosis to those with mucosal damage.

  10. Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy.

    PubMed

    Kopin, A S; McBride, E W; Gordon, M C; Quinn, S M; Beinborn, M

    1997-09-30

    The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer). We now report that the maximal level of receptor-mediated second messenger signaling that can be achieved by these compounds (drug efficacy) markedly differs among species homologs of the CCK-BR. Further analysis reveals that the observed differences in drug efficacy are in large part explained by single or double aliphatic amino acid substitutions between respective species homologs. This interspecies variability in ligand efficacy introduces the possibility of species differences in receptor-mediated function, an important consideration when selecting animal models for preclinical drug testing. The finding that even single amino acid substitutions can significantly affect drug efficacy prompted us to examine ligand-induced signaling by a known naturally occurring human CCK-BR variant (glutamic acid replaced by lysine in position 288; 288E --> K). When examined using the 288E --> K receptor, the efficacies of both PD135,158 and L-740, 093 (S) were markedly increased compared with values obtained with the wild-type human protein. These observations suggest that functional variability resulting from human receptor polymorphisms may contribute to interindividual differences in drug effects.

  11. Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel approach to radionuclide therapy.

    PubMed

    Panigone, S; Nunn, A D

    2006-12-01

    Optimization of therapy for individual patients remains a goal of clinical practice. Radionuclide imaging can identify those patients who may benefit from subsequent targeted therapy by providing regional information on the distribution of the target. An ideal situation may be when the imaging and the therapeutic compounds are the same agent. Two antibodies ([ [90Y]ibritumomab, [131I]tositumomab) are now approved for the systemic radiotherapy of non-Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the more refractory solid tumors paying particular regard to the bone marrow toxicity. The low dose is thought to be a result of the large size of antibodies slowing delivery to the target. Peptides having high affinity to receptors expressed on cancer cells are a promising alternative. They are usually rapidly excreted from the body through renal and/or hepatobiliary excretion thus creating a prolonged accumulation of the radioactivity in the kidneys, which represents a recognized issue for systemic radiotherapy. The first radiopeptide developed was a somatostatin analogue, which led to a major breakthrough in the field. Beside the kidney issue, somatostatin use remains limited to few cancers that express receptors in sufficiently large quantities, mainly neuroendocrine tumors. The gastrin releasing peptide (GRP) receptor is an attractive target for development of new radiopeptides with diagnostic and therapeutic potential. This is based upon the functional expression of GRP receptors in several of the more prevalent cancers including prostate, breast, and small cell lung cancer. This review covers the efforts currently underway to develop new and clinically promising GRP-receptor specific molecules labeled with imageable and therapeutic radionuclides.

  12. Specializations of Gastrin Releasing Peptide Cells of the Mouse Suprachiasmatic Nucleus

    PubMed Central

    Drouyer, Elise; LeSauter, Joseph; Hernandez, Amanda L.; Silver, Rae

    2010-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus regulates daily rhythms in physiology and behavior. It is constituted of a heterogeneous population of cells which together form the circuits underlying its master clock function. Numerous studies suggest the existence of two regions that have been termed core and shell. At a gross level, differences between these regions map to distinct functional differences, though the specific role(s) of various peptidergic cellular phenotypes remains unknown. In mouse, gastrin releasing peptide (GRP) cells lie in the core, are directly retinorecipient and lack detectable rhythmicity in clock gene expression, raising interest in their role in the SCN. Here, we provide evidence that calbindin expressing cells of perinatal mouse SCN express GRP, identified by a green fluorescent protein (GFP+), but lack detectable calbindin later in development. To explore the intra-SCN network in which GRP neurons participate, individual GFP+ cells were filled with tracer and their morphological characteristics, processes, and connections, as well as those of their non-GFP containing immediate neighbors, were compared. The results show that GFP+ neurons form a dense network of local circuits within the core, revealed by appositions on other GFP+ cells and by the presence of dye-coupled cells. Dendrites and axons of GFP+ cells make appositions on arginine vasopressin neurons, while non-GFP cells have a less extensive fiber network, largely confined to the region of GFP+ cells. The results point to specialized circuitry within the SCN, presumably supporting synchronization of neural activity and reciprocal communication between core and shell regions. PMID:20151358

  13. Immunochemical studies on big gastrin using NH2-terminal specific antisera.

    PubMed

    Dockray, G J

    1980-12-01

    Methods are described for obtaining antisera specific for the NH2-terminal regions of human and porcine big gastrin (G34) that can be used in radioimmunoassays. Three antisera have been characterized in detail: one (L66) raised to human 1--15 (Tyr7-Pro8-Ser9) G34 has an antigenic determinant in the 1--6 region of human G34; a second (L107) raised to 1--19 hG34 has an antigenic determinant in the 1--12 region. Both these antisera react weakly with porcine G34. A third antiserum (L33) raised to porcine G34 has an antigenic determinant in the 1--12 region of this peptide, and reacts weakly with human G34. In human antral extracts fractionated on Sephadex G50, L66 and L107 revealed a minor peak of immunoreactivity corresponding to G34, and a major peak corresponding to the NH2-terminal tryptic peptide of G34. Concentrations of the latter peptide were closely similar to those of G17 (i. e.) the COOH-terminal tryptic peptide of G34), consistent with the idea that G34 is cleaved within G-cells by a trypsin-like enzyme to yield G17. Antiserum L33 revealed small amounts of immunoreactivity in antral extracts of dog and cat, but did not reveal significant immunoreactivity in rat antral extracts. In contrast, L66 reacted with rat antral extracts, but not dog or cat. The sequences of G34 in these species are not known, but the results suggest significant differences compared with human and porcine G34, and indicate a high degree of species-specificity with NH2-terminal G34 antisera.

  14. SILENCING GASTRIN-RELEASING PEPTIDE RECEPTOR SUPPRESSES KEY REGULATORS OF AEROBIC GLYCOLYSIS IN NEUROBLASTOMA CELLS

    PubMed Central

    Rellinger, Eric J.; Romain, Carmelle; Choi, SunPhil; Qiao, Jingbo; Chung, Dai H.

    2015-01-01

    Background Under normoxic conditions, cancer cells use aerobic glycolysis as opposed to glucose oxidation for energy production; this altered metabolism correlates with poor outcomes in neuroblastoma. Hypoxia-inducible factor-1α (HIF-1α) and pyruvate dehydrogenase kinase 4 (PDK4) regulate aerobic glycolysis, while pyruvate dehydrogenase phosphatase 2 (PDP2) promotes glucose oxidation. Here, we sought to determine whether gastrin-releasing peptide receptor (GRP-R) signaling regulates glucose metabolism. Procedure Neuroblastoma cell lines, BE(2)-C and SK-N-AS, were used. PCR microararay for glucose metabolism was performed on GRP-R silenced cells. Target protein expression was validated using Western blotting and VEGF ELISA. Cobalt chloride (CoCl2) was used to induce chemical hypoxia. Efficacy of targeting PDK regulation in neuroblastoma was assessed using dichloroacetate (DCA) by conducting cell viability assays and Western blotting for apoptotic markers. Results Silencing GRP-R decreased HIF-1α expression and blocked VEGF expression and secretion in both normoxic and CoCl2 induced hypoxia. PCR array analysis identified that GRP-R silencing reduced PDK4 and increased PDP2 mRNA expression. These findings were validated by Western blotting. CoCl2 induced hypoxia increased VEGF secretion, HIF-1α, and PDK4 expression. PDK4 silencing decreased HIF-1α expression and VEGF expression and secretion. DCA treatment decreased BE(2)-C and SK-N-AS proliferation while promoting cell death. GRP-R silencing and DCA treatment synergistically halted BE(2)-C proliferation. Conclusions We report that GRP-R regulates glucose metabolism in neuroblastoma by modulating HIF-1α, PDK4 and PDP2. PDK4 regulates glucose metabolism, in part, via regulation of HIF-1α. Synergistic consequences of GRP-R inhibition and DCA treatment may suggest a novel therapeutic strategy for the treatment of aggressive neuroblastoma. PMID:25630799

  15. Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin.

    PubMed

    Song, Imane; Patel, Oelfah; Himpe, Eddy; Muller, Christo J F; Bouwens, Luc

    2015-01-01

    One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The

  16. Gastrin releasing peptide-29 requires vagal and splanchnic neurons to evoke satiation and satiety.

    PubMed

    Wright, Susan A; Washington, Martha C; Garcia, Carlos; Sayegh, Ayman I

    2012-01-01

    We have shown that gastrin-releasing peptide-29 (GRP-29), the large molecular form of GRP in rats, reduces meal size (MS, intake of 10% sucrose solution) and prolongs the intermeal interval (IMI). In these studies, we first investigated possible pathways for these responses in rats undergoing total subdiaphragmatic vagotomy (VGX, removal of vagal afferent and efferent innervation of the gut), celiaco-mesenteric ganglionectomy (CMGX, removal of splanchnic afferent and efferent innervation of the gut) and combined VGX and CMGX. Second, we examined if the duodenum communicates the feeding signals (MS and IMI) of GRP-29 (0, 0.3, 1.0, 2.1, 4.1, 10.3 and 17.2 nmol/kg) with the feeding control areas of the hindbrain by performing duodenal myotomy (MYO), a procedure that severs some layers of the duodenal wall including the vagal, splanchnic and enteric neurons. We found that GRP-29 (2.1, 4.1, 10.3, 17.2 nmol/kg) reduced the size of the first meal (10% sucrose) and (1, 4.1, 10.3 nmol/kg) prolongs the first IMI but did not affect the subsequent meals or IMIs. In addition, CMGX and combined VGX/CMGX attenuated reduction of MS by GRP-29 and all surgeries attenuated the prolongation of the IMI. Therefore, reduction of MS and prolongation of IMI by GRP-29 require vagal and splanchnic nerves, and the duodenum is the major conduit that communicates prolongation of IMI by GRP-29 with the brain.

  17. Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide, gastrin and cholecystokinin octapeptide

    PubMed Central

    Zhang, Zhen-Hai; Qin, Cheng-Kun; Wu, Shuo-Dong; Xu, Jian; Cui, Xian-Ping; Wang, Zhi-Yi; Xian, Guo-Zhe

    2014-01-01

    AIM: To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs. METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups: the control group and pigment stone group. The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice, and were fed a pigment lithogenic diet and sacrificed after 3, 6, 9 and 12 wk. SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage. Serum vasoactive intestinal peptide (VIP), gastrin and cholecystokinin octapeptide (CCK-8) were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay. RESULTS: The incidence of pigment gallstone formation was 0%, 0%, 16.7% and 66.7% in the 3-, 6-, 9- and 12-wk group, respectively. The frequency of myoelectric activity decreased in the 3-wk group. The amplitude of myoelectric activity had a tendency to decrease but not significantly. The frequency of the SO decreased significantly in the 9-wk group. The SO basal pressure and common bile duct pressure increased in the 12-wk group (25.19 ± 7.77 mmHg vs 40.56 ± 11.81 mmHg, 22.35 ± 7.60 mmHg vs 38.51 ± 11.57 mmHg, P < 0.05). Serum VIP was significantly elevated in the 6- and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group. CONCLUSION: Pigment gallstone-causing diet may induce SO dysfunction. The tension of the SO increased. The disturbance in SO motility may play a role in pigment gallstone formation, and changes in serum VIP and CCK-8 may be important causes of SO dysfunction. PMID:24782626

  18. Gastrin-releasing peptide contributes to the regulation of adult hippocampal neurogenesis and neuronal development.

    PubMed

    Walton, Noah M; de Koning, Anoek; Xie, Xiuyuan; Shin, Rick; Chen, Qian; Miyake, Shinichi; Tajinda, Katsunori; Gross, Adam K; Kogan, Jeffrey H; Heusner, Carrie L; Tamura, Kouichi; Matsumoto, Mitsuyuki

    2014-09-01

    In the postnatal hippocampus, newly generated neurons contribute to learning and memory. Disruptions in neurogenesis and neuronal development have been linked to cognitive impairment and are implicated in a broad variety of neurological and psychiatric disorders. To identify putative factors involved in this process, we examined hippocampal gene expression alterations in mice possessing a heterozygous knockout of the calcium/calmodulin-dependent protein kinase II alpha heterozygous knockout gene (CaMK2α-hKO), an established model of cognitive impairment that also displays altered neurogenesis and neuronal development. Using this approach, we identified gastrin-releasing peptide (GRP) as the most dysregulated gene. In wild-type mice, GRP labels NeuN-positive neurons, the lone exception being GRP-positive, NeuN-negative cells in the subgranular zone, suggesting GRP expression may be relevant to neurogenesis and/or neuronal development. Using a model of in vitro hippocampal neurogenesis, we determined that GRP signaling is essential for the continued survival and development of newborn neurons, both of which are blocked by transient knockdown of GRP's cognate receptor (GRPR). Furthermore, GRP appears to negatively regulate neurogenesis-associated proliferation in neural stem cells both in vitro and in vivo. Intracerebroventricular infusion of GRP resulted in a decrease in immature neuronal markers, increased cAMP response element-binding protein (CREB) phosphorylation, and decreased neurogenesis. Despite increased levels of GRP mRNA, CaMK2α-hKO mutant mice expressed reduced levels of GRP peptide. This lack of GRP may contribute to the elevated neurogenesis and impaired neuronal development, which are reversed following exogenous GRP infusion. Based on these findings, we hypothesize that GRP modulates neurogenesis and neuronal development and may contribute to hippocampus-associated cognitive impairment.

  19. Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs.

    PubMed Central

    Konturek, S J; Dembinski, A; Krol, R; Wünsch, E

    1977-01-01

    1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs. 2. The motilin-induced stimulation of gastric secretion occurred independently of antral pH and was not accompanied by any alteration in the serum gastrin level suggesting that motilin did not affect the release of gastrin. 3. When infused intravenously in a constant dose against a constant background stimulation with pentagastrin or histamine 13-nle-motilin inhibited both acid and pepsin secretion from the main stomach and fundic pouch. 4. The inhibitory effect of 13-nle-motilin was always associated with a marked reduction in mucosal blood flow but without any change in the ratio of aminopyrine concentration in the gastric juice and blood plasma indicating that this peptide primarily affected gastric secretion but did not limit the gastric mucosal microcirculation. PMID:321755

  20. Modulation of phagocytic function in murine peritoneal macrophages by bombesin, gastrin-releasing peptide and neuromedin C.

    PubMed Central

    De la Fuente, M; Del Rio, M; Ferrandez, M D; Hernanz, A

    1991-01-01

    Bombesin, as well as the two mammalian bombesin-like peptides gastrin-releasing peptide and neuromedin C, have been shown in this study to stimulate in vitro all steps of the phagocytic process in murine peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of cells (Candida albicans) and inert particles (latex beads), and production of superoxide anion as measured by nitroblue tetrazolium reduction. A dose-response relationship was observed, with maximal stimulation of phagocytic process between 10(-12)M and 10(-9)M. Gastrin-releasing peptide (GRP) and neuromedin C caused a higher activation of adherence, chemotaxis and ingestion of C. albicans than bombesin. The three neuropeptides induced in murine macrophages a significant, but transient, increase of inositol 1,4,5-trisphosphate (IP3) levels at 60 seconds. On the contrary, these neuropeptides produced a rapid, transient and significant decrease of cAMP at 30 seconds. These results suggest that there are close relations between IP3 and cAMP messenger systems and the phagocytic process in murine peritoneal macrophages when these cells are incubated in the presence of bombesin, GRP or neuromedin C. PMID:1649124

  1. Paracrine effects of bombesin/gastrin-releasing peptide and other growth factors on pulmonary neuroendocrine cells in vitro.

    PubMed

    Speirs, V; Bienkowski, E; Wong, V; Cutz, E

    1993-05-01

    Pulmonary neuroendocrine cells (PNEC) are numerous in the fetus where they have been implicated to have a role in fetal lung development. We assessed the effects of putative growth factors, gastrin releasing peptide (GRP), cholecystokinin (CCK), gastrin (GN), serotonin (5-HT), and epidermal growth factor (EGF), some of which are produced by PNEC, either alone or in combination, on cultured fetal rabbit PNEC from 20, 24, and 28 day fetuses. GRP increased the total protein of the cultures over a 7 day period in an age-dependent manner, with greatest effect in cultures from the 24 day fetus, no effect with the 28 day fetus, and an inhibitory effect on 20 day cultures. This was accompanied by an increase in PNEC, which could be blocked by treatment of the cultures with a monoclonal antibody to GRP (2A11). There was no increase in 3H-thymidine labeling of PNEC in GRP treated cultures but an increase in numbers of cells partially stained for 5-HT, suggesting the induction of a precursor cell. Other growth factors had neither an inhibitory nor a stimulatory effect either alone or in combination with GRP. Preliminary studies with 125I-GRP receptor localization suggests that the GRP receptor is mostly expressed on pulmonary fibroblasts, and less on epithelial cells, so that the role for GRP in fetal lung development, at least in the rabbit, is probably indirect, acting via a paracrine mechanism.

  2. Critical evaluation of the expression of gastrin-releasing peptide in dorsal root ganglia and spinal cord

    PubMed Central

    Barry, Devin M; Li, Hui; Liu, Xian-Yu; Shen, Kai-Feng; Liu, Xue-Ting; Wu, Zhen-Yu; Munanairi, Admire; Chen, Xiao-Jun; Yin, Jun; Sun, Yan-Gang; Li, Yun-Qing

    2016-01-01

    There are substantial disagreements about the expression of gastrin-releasing peptide (GRP) in sensory neurons and whether GRP antibody cross-reacts with substance P (SP). These concerns necessitate a critical revaluation of GRP expression using additional approaches. Here, we show that a widely used GRP antibody specifically recognizes GRP but not SP. In the spinal cord of mice lacking SP (Tac1 KO), the expression of not only GRP but also other peptides, notably neuropeptide Y (NPY), is significantly diminished. We detected Grp mRNA in dorsal root ganglias using reverse transcription polymerase chain reaction, in situ hybridization and RNA-seq. We demonstrated that Grp mRNA and protein are upregulated in dorsal root ganglias, but not in the spinal cord, of mice with chronic itch. Few GRP+ immunostaining signals were detected in spinal sections following dorsal rhizotomy and GRP+ cell bodies were not detected in dissociated dorsal horn neurons. Ultrastructural analysis further shows that substantially more GRPergic fibers form synaptic contacts with gastrin releasing peptide receptor-positive (GRPR+) neurons than SPergic fibers. Our comprehensive study demonstrates that a majority of GRPergic fibers are of primary afferent origin. A number of factors such as low copy number of Grp transcripts, small percentage of cells expressing Grp, and the use of an eGFP GENSAT transgenic as a surrogate for GRP protein have contributed to the controversy. Optimization of experimental procedures facilitates the specific detection of GRP expression in dorsal root ganglia neurons. PMID:27068287

  3. Relative distribution of gastrin-, CCK-8-, NPY- and CGRP-immunoreactive cells in the digestive tract of dorado (Salminus brasiliensis).

    PubMed

    Pereira, R T; Costa, L S; Oliveira, I R C; Araújo, J C; Aerts, M; Vigliano, F A; Rosa, P V

    2015-04-01

    The endocrine cells (ECs) of the gastrointestinal mucosa form the largest endocrine system in the body, not only in terms of cell numbers but also in terms of the different produced substances. Data describing the association between the relative distributions of the peptide-specific ECs in relation to feeding habits can be useful tools that enable the creation of a general expected pattern of EC distribution. We aimed to investigate the distribution of ECs immunoreactive for the peptides gastrin (GAS), cholecystokinin (CCK-8), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in different segments of the digestive tract of carnivorous fish dorado (Salminus brasiliensis) by using immunohistochemistry procedures. The distribution of endocrine cells immunoreactive for gastrin (GAS), cholecystokinin (CCK-8), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in digestive tract of dorado S. brasiliensis was examined by immunohistochemistry. The results describe the association between the distribution of the peptide-specific endocrine cells and feeding habits in different carnivorous fish. The largest number of endocrine cells immunoreactive for GAS, CCK-8, and CGRP were found in the pyloric stomach region and the pyloric caeca. However, NPY-immunoreactive endocrine cells were markedly restricted to the midgut. The distribution pattern of endocrine cells identified in S. brasiliensis is similar to that found in other carnivorous fishes.

  4. Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells.

    PubMed

    Masià-Balagué, Miriam; Izquierdo, Ismael; Garrido, Georgina; Cordomí, Arnau; Pérez-Benito, Laura; Miller, Nichol L G; Schlaepfer, David D; Gigoux, Véronique; Aragay, Anna M

    2015-06-12

    The guanine nucleotide exchange factor Rgnef (also known as ArhGEF28 or p190RhoGEF) promotes colon carcinoma cell motility and tumor progression via interaction with focal adhesion kinase (FAK). Mechanisms of Rgnef activation downstream of integrin or G protein-coupled receptors remain undefined. In the absence of a recognized G protein signaling homology domain in Rgnef, no proximal linkage to G proteins was known. Utilizing multiple methods, we have identified Rgnef as a new effector for Gα13 downstream of gastrin and the type 2 cholecystokinin receptor. In DLD-1 colon carcinoma cells depleted of Gα13, gastrin-induced FAK Tyr(P)-397 and paxillin Tyr(P)-31 phosphorylation were reduced. RhoA GTP binding and promoter activity were increased by Rgnef in combination with active Gα13. Rgnef co-immunoprecipitated with activated Gα13Q226L but not Gα12Q229L. The Rgnef C-terminal (CT, 1279-1582) region was sufficient for co-immunoprecipitation, and Rgnef-CT exogenous expression prevented Gα13-stimulated SRE activity. A domain at the C terminus of the protein close to the FAK binding domain is necessary to bind to Gα13. Point mutations of Rgnef-CT residues disrupt association with active Gα13 but not Gαq. These results show that Rgnef functions as an effector of Gα13 signaling and that this linkage may mediate FAK activation in DLD-1 colon carcinoma cells.

  5. Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells*

    PubMed Central

    Masià-Balagué, Miriam; Izquierdo, Ismael; Garrido, Georgina; Cordomí, Arnau; Pérez-Benito, Laura; Miller, Nichol L. G.; Schlaepfer, David D.; Gigoux, Véronique; Aragay, Anna M.

    2015-01-01

    The guanine nucleotide exchange factor Rgnef (also known as ArhGEF28 or p190RhoGEF) promotes colon carcinoma cell motility and tumor progression via interaction with focal adhesion kinase (FAK). Mechanisms of Rgnef activation downstream of integrin or G protein-coupled receptors remain undefined. In the absence of a recognized G protein signaling homology domain in Rgnef, no proximal linkage to G proteins was known. Utilizing multiple methods, we have identified Rgnef as a new effector for Gα13 downstream of gastrin and the type 2 cholecystokinin receptor. In DLD-1 colon carcinoma cells depleted of Gα13, gastrin-induced FAK Tyr(P)-397 and paxillin Tyr(P)-31 phosphorylation were reduced. RhoA GTP binding and promoter activity were increased by Rgnef in combination with active Gα13. Rgnef co-immunoprecipitated with activated Gα13Q226L but not Gα12Q229L. The Rgnef C-terminal (CT, 1279–1582) region was sufficient for co-immunoprecipitation, and Rgnef-CT exogenous expression prevented Gα13-stimulated SRE activity. A domain at the C terminus of the protein close to the FAK binding domain is necessary to bind to Gα13. Point mutations of Rgnef-CT residues disrupt association with active Gα13 but not Gαq. These results show that Rgnef functions as an effector of Gα13 signaling and that this linkage may mediate FAK activation in DLD-1 colon carcinoma cells. PMID:25922072

  6. Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk.

    PubMed

    Pohjanen, Vesa-Matti; Koivurova, Olli-Pekka; Huhta, Heikki; Helminen, Olli; Mäkinen, Johanna M; Karhukorpi, Jari M; Joensuu, Tapio; Koistinen, Pentti O; Valtonen, Jarno M; Niemelä, Seppo E; Karttunen, Riitta A; Karttunen, Tuomo J

    2015-01-01

    Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.

  7. Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca2+ channels.

    PubMed

    Björkqvist, Maria; Bernsand, Maria; Eliasson, Lena; Håkanson, Rolf; Lindström, Erik

    2005-08-15

    The oxyntic mucosa is rich in ECL cells. They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP). Secretion is initiated by Ca2+ entry. While gastrin stimulates secretion by opening L-type and N-type Ca2+ channels, PACAP stimulates secretion by activating L-type and receptor-operated Ca2+ channels. Somatostatin, galanin and prostaglandin E2 (PGE2) inhibit gastrin- and PACAP-stimulated secretion from the ECL cells. In the present study, somatostatin and the PGE2 congener misoprostol inhibited gastrin- and PACAP-stimulated secretion 100%, while galanin inhibited at most 60-65%. Bay K 8644, a specific activator of L-type Ca2+ channels, stimulated ECL-cell secretion, an effect that was inhibited equally effectively by somatostatin, misoprostol and galanin (75-80% inhibition). Pretreatment with pertussis toxin, that inactivates inhibitory G-proteins, prevented all three agents from inhibiting stimulated secretion (regardless of the stimulus). Pretreatment with nifedipine (10 microM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50-60%, gastrin-evoked secretion by approximately 80% and abolished the response to Bay K 8644. The nifedipine-resistant response to PACAP was abolished by somatostatin and misoprostol but not by galanin. Gastrin and PACAP raised the intracellular Ca2+ concentration in a biphasic manner, believed to reflect mobilization of internal Ca2+ followed by Ca2+ entry. Somatostatin and misoprostol blocked Ca2+ entry (and histamine and pancreastatin secretion) but not mobilization of internal Ca2+. The present observations on isolated ECL cells suggest that Ca2+ entry rather than mobilization of internal Ca2+ triggers exocytosis, that gastrin and PACAP activate different (but over-lapping) Ca2+ channels, that somatostatin, misoprostol and galanin interact with inhibitory G-proteins to block Ca2+ entry via L-type Ca

  8. Role of gastrin in the development of gastric mucosa, ECL cells and A-like cells in newborn and young rats.

    PubMed

    Björkqvist, Maria; Dornonville de la Cour, Charlotta; Zhao, Chun-Mei; Gagnemo-Persson, Rebecca; Håkanson, Rolf; Norlén, Per

    2002-10-15

    Histamine-producing ECL cells and ghrelin-producing A-like cells are endocrine/paracrine cell populations in the acid-producing part of the rat stomach. While the A-like cells operate independently of gastrin, the ECL cells respond to gastrin with mobilization of histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. Gastrin is often assumed to be the driving force behind the postnatal development of the gastric mucosa in general and the ECL cells in particular. We tested this assumption by examining the oxyntic mucosa (with ECL cells and A-like cells) in developing rats under the influence of YF476, a cholecystokinin-2 (CCK(2)) receptor antagonist. The drug was administered by weekly subcutaneous injections starting at birth. The body weight gain was not affected. Weaning occurred at days 15-22 in both YF476-treated and age-matched control rats. Circulating gastrin was low at birth and reached adult levels 2 weeks after birth. During and after weaning (but not before), YF476 greatly raised the serum gastrin concentration (because of abolished acid feedback inhibition of gastrin release). The weight of the stomach was unaffected by YF476 during the first 2-3 weeks after birth. From 4 to 5 weeks of age, the weight and thickness of the gastric mucosa were lower in YF476-treated rats than in controls. Pancreastatin-immunoreactive cells (i.e. all endocrine cells in the stomach) and ghrelin-immunoreactive cells (A-like cells) were few at birth and increased gradually in number until 6-8 weeks of age (control rats). At first, YF476 did not affect the development of the pancreastatin-immunoreactive cells, but a few weeks after weaning, the cells were fewer in the YF476 rats. The ECL-cell parameters (oxyntic mucosal histamine and pancreastatin concentrations, the histidine decarboxylase (HDC) activity, the HDC mRNA levels and serum pancreastatin concentration) increased slowly until weaning in both YF476-treated and control rats. From then on, there

  9. Syndromic versus non-syndromic sporadic gastrin-producing neuroendocrine tumors of the duodenum: comparison of pathological features and biological behavior.

    PubMed

    Rosentraeger, M Johannes; Garbrecht, Nele; Anlauf, Martin; Raffel, Andreas; Knoefel, Wolfram T; Wiedenmann, Bertram; Klöppel, Günter

    2016-03-01

    Sporadic gastrin-producing neuroendocrine tumors of the duodenum present either with the Zollinger-Ellison syndrome (ZES) or with unspecific symptoms. While syndromic gastrin-producing neuroendocrine tumors often show metastases at the time of diagnosis, those without a syndrome do not. The aim of the study was to search for clinicopathological features that may distinguish the two categories of gastrin-producing duodenal tumors. In a retrospective study, we analyzed the clinical and pathological data in a series of 41 patients with syndromic (i.e., gastrinomas) or non-syndromic duodenal gastrin-producing neuroendocrine tumors (ns-gas-NETs). Twenty-four (59 %) of the 41 patients had tumors that were associated with a ZES and were classified as gastrinomas. These tumors showed a higher Ki-67 index than that of the ns-gas-NETs (1.74 vs. 0.85 %, p = 0.012). In addition, they had more lymph node metastases (75 vs. 6 %, p < 0.001) and showed liver metastases and thus presented much more frequently in TNM stage ≥III (75 vs. 6 %; p < 0.001) than their non-syndromic counterparts. Gastrinomas were removed surgically, ns-gas-NETs endoscopically. We did not observe any significant differences in overall survival or recurrence of disease. Duodenal gastrinomas show no clear morphological features that distinguish them from their non-syndromic counterparts. However, the patients with gastrinomas present in a more advanced stage of disease and need surgical treatment, while non-syndromic gastrin-producing duodenal NETs may be cured by complete endoscopical removal.

  10. Deciding about hormone therapy

    MedlinePlus

    HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - deciding

  11. Calcitonin, the forgotten hormone: does it deserve to be forgotten?

    PubMed Central

    Felsenfeld, Arnold J.; Levine, Barton S.

    2015-01-01

    Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. Calcitonin has been preserved during the transition from ocean-based life to land dwellers and is phylogenetically older than parathyroid hormone. Calcitonin secretion is stimulated by increases in the serum calcium concentration and calcitonin protects against the development of hypercalcemia. Calcitonin is also stimulated by gastrointestinal hormones such as gastrin. This has led to the unproven hypothesis that postprandial calcitonin stimulation could play a role in the deposition of calcium and phosphate in bone after feeding. However, no bone or other abnormalities have been described in states of calcitonin deficiency or excess except for diarrhea in a few patients with medullary thyroid carcinoma. Calcitonin is known to stimulate renal 1,25 (OH)2 vitamin D (1,25D) production at a site in the proximal tubule different from parathyroid hormone and hypophosphatemia. During pregnancy and lactation, both calcitonin and 1,25D are increased. The increases in calcitonin and 1,25D may be important in the transfer of maternal calcium to the fetus/infant and in the prevention and recovery of maternal bone loss. Calcitonin has an immediate effect on decreasing osteoclast activity and has been used for treatment of hypercalcemia. Recent studies in the calcitonin gene knockout mouse have shown increases in bone mass and bone formation. This last result together with the presence of calcitonin receptors on the osteocyte suggests that calcitonin could possibly affect osteocyte products which affect bone formation. In summary, a precise role for calcitonin remains elusive more than 50 years after its discovery. PMID:25815174

  12. [Hormonal dysnatremia].

    PubMed

    Karaca, P; Desailloud, R

    2013-10-01

    Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.

  13. Gastrin induces sodium-hydrogen exchanger 3 phosphorylation and mTOR activation via a phosphoinositide 3-kinase-/protein kinase C-dependent but AKT-independent pathway in renal proximal tubule cells derived from a normotensive male human.

    PubMed

    Liu, Tianbing; Jose, Pedro A

    2013-02-01

    Gastrin is natriuretic, but its renal molecular targets and signal transduction pathways are not fully known. In this study, we confirmed the existence of CCKBR (a gastrin receptor) in male human renal proximal tubule cells and discovered that gastrin induced S6 phosphorylation, a downstream component of the phosphatidylinositol 3 kinase (PI3 kinase)-mammalian target of rapamycin pathway. Gastrin also increased the phosphorylation of sodium-hydrogen exchanger 3 (NHE3) at serine 552, caused its internalization, and decreased its expression at the cell surface and NHE activity. The phosphorylation of NHE3 and S6 was dependent on PI3 kinases because it was blocked by 2 different PI3-kinase inhibitors, wortmannin and LY294,002. The phosphorylation of NHE3 and S6 was not affected by the protein kinase A inhibitor H-89 but was blocked by a pan-PKC (chelerythrine) and a conventional PKC (cPKC) inhibitor (Gö6976) (10 μM) and an intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The cPKC involved was probably PKCα because it was phosphorylated by gastrin. The gastrin-mediated phosphorylation of NHE3, S6, and PKCα was via phospholipase C because it was blocked by a phospholipase C inhibitor, U73122 (10 μM). The phosphorylation (activation) of AKT, which is usually upstream of mammalian target of rapamycin in the classic PI3 kinase-AKT-p70S6K signaling pathway, was not affected, suggesting that the gastrin-induced phosphorylation of NHE3 and S6 is dependent on both PI3 kinase and PKCα but not AKT.

  14. Postnatal development of the gastrin-releasing peptide system in the lumbosacral spinal cord controlling male reproductive function in rats.

    PubMed

    Katayama, Nao; Oti, Takumi; Takanami, Keiko; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2016-01-01

    A sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord, which projects to the lower spinal centers, controls erection and ejaculation in rats. However, little is known about the postnatal development of this system. In this study, we therefore examined the postnatal development of the male-dominant spinal GRP system and its sexual differentiation in rats using immunohistochemistry. Our results show that male-dominant expression of GRP is prominent from the onset of puberty and that sexually dimorphism persists into adulthood. These results suggest that androgen surge during male puberty plays an important role in the development and maintenance of the male-specific GRP function in the rat spinal cord.

  15. Postnatal development of the gastrin-releasing peptide system in the lumbosacral spinal cord controlling male reproductive function in rats

    PubMed Central

    KATAYAMA, Nao; OTI, Takumi; TAKANAMI, Keiko; SAKAMOTO, Tatsuya; SAKAMOTO, Hirotaka

    2016-01-01

    A sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord, which projects to the lower spinal centers, controls erection and ejaculation in rats. However, little is known about the postnatal development of this system. In this study, we therefore examined the postnatal development of the male-dominant spinal GRP system and its sexual differentiation in rats using immunohistochemistry. Our results show that male-dominant expression of GRP is prominent from the onset of puberty and that sexually dimorphism persists into adulthood. These results suggest that androgen surge during male puberty plays an important role in the development and maintenance of the male-specific GRP function in the rat spinal cord. PMID:26860455

  16. Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome.

    PubMed

    Zwirska-Korczala, K; Konturek, S J; Sodowski, M; Wylezol, M; Kuka, D; Sowa, P; Adamczyk-Sowa, M; Kukla, M; Berdowska, A; Rehfeld, J F; Bielanski, W; Brzozowski, T

    2007-03-01

    Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease

  17. Hormone therapy in acne.

    PubMed

    Lakshmi, Chembolli

    2013-01-01

    Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

  18. The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones.

    PubMed

    Meek, Claire L; Lewis, Hannah B; Reimann, Frank; Gribble, Fiona M; Park, Adrian J

    2016-03-01

    Bariatric surgery for obesity has proved to be an extremely effective method of promoting long-term weight reduction with additional beneficial metabolic effects, such as improved glucose tolerance and remission of type 2 diabetes. A range of bariatric procedures are in common use, including gastric banding, sleeve gastrectomy and the Roux-en-Y gastric bypass. Although the mechanisms underlying the efficacy of bariatric surgery are unclear, gastrointestinal and pancreatic peptides are thought to play an important role. The aim of this review is to summarise the effects of different bariatric surgery procedures upon gastrointestinal and pancreatic peptides, including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic hormone (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin, insulin, glucagon and somatostatin.

  19. Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide. Selective O-deprotection of tyrosine.

    PubMed

    Barlos, K; Gatos, D; Kapolos, S; Poulos, C; Schäfer, W; Yao, W Q

    1991-12-01

    The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH2, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (Leu15)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloromethane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCK-octapeptide.

  20. Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice

    PubMed Central

    Fukui, T; Nishio, A; Okazaki, K; Uza, N; Ueno, S; Kido, M; Inoue, S; Kitamura, H; Kiriya, K; Ohashi, S; Asada, M; Tamaki, H; Matsuura, M; Kawasaki, K; Suzuki, K; Uchida, K; Fukui, H; Nakase, H; Watanabe, N; Chiba, T

    2006-01-01

    Background and aim Major histocompatibility complex class II deficient (Aα0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aα0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aα0/0 mice. Methods Stomachs from 1–6 month old Aα0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll‐like receptors (TLRs), cyclooxygenase (COX)‐2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. Results Aα0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti‐Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1β, interferon γ, TLR‐2, TLR‐4, and COX‐2 were upregulated, and MPO activity was increased. Only a small amount of non‐pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg‐Iα positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. Conclusion Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aα0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS. PMID:16322110

  1. Standardization of hormone determinations.

    PubMed

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization.

  2. Alkaloids from Mahonia bealei posses anti-H⁺/K⁺-ATPase and anti-gastrin effects on pyloric ligation-induced gastric ulcer in rats.

    PubMed

    Zhang, Su-Li; Li, Hui; He, Xin; Zhang, Run-Qi; Sun, Yu-He; Zhang, Chun-Feng; Wang, Chong-Zhi; Yuan, Chun-Su

    2014-09-25

    The purpose of this study was to investigate the underlying mechanism(s) of the total alkaloids (TA) from Mahonia bealei in treating pyloric ligation-induced gastric ulcers in rats. Animals were sacrificed after 19 h of the ligation. Gastric acid, peptic activities, mucin levels, H(+)/K(+)-ATPase activities and the gastrin level were analyzed. To improve the accuracy of the observations, IPP 6.0 software was introduced to measure the area of ulcer. TA (18.56 mg/kg/day, i.g.) showed an antiulcer effect by significantly decreasing the gastric ulcer areas (11.28 mm(2)) compared with model group (26.36 mm(2)). The TA ulcer inhibition ratio was 57.2%, compared with the effect of the positive control, omeprazole (62.96%). The results also showed that TA had a significant effect in inhibiting the release of H(+)/K(+)-ATPase, reducing the content of gastrin and decreasing gastric acidity on experimental animals. However, the TA had no significant effects on gastric mucus secretion and pepsin activity. Data indicated that TA had gastric ulcer protective effects by modulating the H(+)/K(+)-ATPase activity and gastrin level. TA has a potential to be developed as a pharmacological agent for the treatment of gastric ulcers.

  3. Hormonal effects in newborns

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb babies ...

  4. Hormone Health Network

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... to hormones! Download our Free App! Understand the endocrine system and its related conditions with our 3D Patient ...

  5. Growth hormone deficiency

    MedlinePlus

    ... dosage of the medicine. Serious side effects of growth hormone treatment are rare. Common side effects include: Headache Fluid ... years. The rate of growth then slowly decreases. Growth hormone therapy does not work for all children. Left untreated, ...

  6. Hormones and Obesity

    MedlinePlus

    ... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...

  7. [Thyroid hormone resistance syndromes].

    PubMed

    Bernal, Juan

    2011-04-01

    Thyroid hormone resistance syndromes are a group of genetic conditions characterized by decreased tissue sensitivity to thyroid hormones. Three syndromes, in which resistance to hormone action is respectively due to mutations in the gene encoding for thyroid hormone receptor TRβ, impaired T4 and T3 transport, and impaired conversion of T4 to T3 mediated by deiodinases. An updated review of each of these forms of resistance is provided, and their pathogenetic mechanisms and clinical approaches are discussed.

  8. Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy.

    PubMed

    Konturek, Peter C; Rembiasz, Kazimierz; Konturek, Stanislaw J; Stachura, Jerzy; Bielanski, Wladyslaw; Galuschka, K; Karcz, Danuta; Hahn, Eckhart G

    2003-01-01

    H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 x 20 mg), amoxycillin (2 x 1 g) and clarithromycin (2 x 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic

  9. [Growth hormone treatment update].

    PubMed

    2014-02-01

    Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

  10. Characterization of gastrin-releasing peptide immunoreactivity in distinct storage particles in guinea pig myenteric and Torpedo electromotor neurones.

    PubMed

    Shaw, C; Whittaker, V P; Agoston, D V

    1990-01-01

    Using high resolution centrifugal density-gradient separation of cytoplasmic extracts of guinea pig myenteric plexus and Torpedo electric tissue, we have succeeded in isolating fractions of storage particles rich in gastrin-releasing peptide (GRP). In extracts of myenteric plexus and gradients derived therefrom, the 10-amino acid GRP peptide (GRP-10) was the sole form present; this was bimodally distributed in the gradients, one peak copurifying with Golgi membranes and apparently consisting of immature storage particles, the other with other synaptophysin-rich neuropeptide-containing particles. In extracts of electric organ, a tissue rich in cholinergic electromotor nerve terminals, and gradients derived therefrom, GRP-like immunoreactivity behaved in gel permeation and reversed phase high performance liquid chromatography like the 27-amino acid peptide (GRP-27). About half of the immunoreactivity sedimented in the centrifugal gradient to a region rich in particles containing vasoactive intestinal polypeptide-like immunoreactivity; the remainder was recovered in a very dense region of the gradient containing larger membrane fragments, including synaptosomes. The electromotor nerves and cell bodies also contained GRP-27-like immunoreactivity in relatively high concentration as did the Torpedo gut. It is concluded that this GRP-like peptide is packaged in dense storage particles in the electromotor neurones.

  11. AG-041R, a cholecystokinin-B/gastrin receptor antagonist, stimulates the repair of osteochondral defect in rabbit model.

    PubMed

    Nakanishi, Toru; Kawasaki, Kenzo; Uchio, Yuji; Kataoka, Hiroko; Terashima, Masaharu; Ochi, Mitsuo

    2002-03-29

    A newly synthesized compound (AG-041R), 3R-1-(2,2Diethoxyethyl)-((4methylphenyl) amino-carbonyl methyl)-3-((4methylphenyl) ureido-indoline-2-one), is a cholecystokinin-B/gastrin receptor antagonist which has stimulatory effects on the matrix synthesis of chondrocytes in vitro. In this study, we examined the effect of AG-041R on the repair of osteochondral defects (cylindrical, 4 mm diameter) in the patellar groove of the rabbit knee joint. At the time of operation, 100 microl of 1 microM of AG-041R was administered, followed by 200 microl with an osmotic pump for 14 days. Histological and biochemical evaluations were performed at 12 and 24 weeks after surgery. The histological score of the AG-041R-treated group, the quantity of glycosaminoglycan and the ratio of chondroitin sulfate in the AG-041R-treated tissue were significantly higher than in the untreated group. Moreover, the degeneration of cartilage around the defect was suppressed in the AG-041R-treated group. These findings suggest that AG-041R is effective for the repair of osteochondral defects.

  12. Long-Term Treatment Sequelae After External Beam Irradiation With or Without Hormonal Manipulation for Adenocarcinoma of the Prostate: Analysis of Radiation Therapy Oncology Group Studies 85-31, 86-10, and 92-02

    SciTech Connect

    Lawton, Colleen A. Bae, Kyoungwha; Pilepich, Miljenko; Hanks, Gerald; Shipley, William

    2008-02-01

    Purpose: Late gastrointestinal (GI) and genitourinary (GU) morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians and patients alike. In addition, for locally advanced/high-risk cancer, the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large Radiation Therapy Oncology Group (RTOG) studies (85-31, 86-10, and 92-02) to try to address these issues. Methods and Materials: A total of 2,922 patients were accrued with a median follow-up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was Grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short-course hormone therapy (STH) vs. RT + long-term hormone therapy (LTH). Results: Multivariate analysis reveals that age >70 was statistically significantly associated with a decrease in late any Grade 3+ toxicity (hazard ratio [HR] = 0.78, p = 0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of Grade 3+ GI, GU, and other toxicity compared with RT alone (p = .00006; p = 0.0037; p = 0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of Grade 3+ GU toxicity compared with RT alone (p = 0.023). Conclusions: These data show that external beam radiation therapy remains a safe option for locally advanced/high-risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment.

  13. The novel GLP-1-gastrin dual agonist ZP3022 improves glucose homeostasis and increases β-cell mass without affecting islet number in db/db mice.

    PubMed

    Dalbøge, Louise S; Almholt, Dorthe L C; Neerup, Trine S R; Vrang, Niels; Jelsing, Jacob; Fosgerau, Keld

    2014-08-01

    Antidiabetic treatments aiming to preserve or even to increase β-cell mass are currently gaining increased interest. Here we investigated the effect of chronic treatment with the novel glucagon-like peptide-1 (GLP-1)-gastrin dual agonist ZP3022 (HGEGTFTSDLSKQMEEEAVRLFIEWLKN-8Ado-8Ado-YGWLDF-NH2) on glycemic control, β-cell mass and proliferation, and islet number. Male db/db mice were treated with ZP3022, liraglutide, or vehicle for 2, 4, or 8 weeks, with terminal assessment of hemoglobin A1c, basal blood glucose, and plasma insulin concentrations. Pancreata were removed for immunohistochemical staining and stereological quantification of β-cell mass, islet numbers, proliferation, and apoptosis. Treatment with ZP3022 or liraglutide led to a significant improvement in glycemic control. ZP3022 treatment resulted in a sustained increase in β-cell mass after 4 and 8 weeks of treatment, whereas the effect of liraglutide was transient. The expansion in β-cell mass observed in the ZP3022-treated mice appeared to be driven by increased β-cell proliferation in existing islets rather than by formation of new islets, as mean islet mass increased but the number of islets remained constant. Our data demonstrate that the GLP-1-gastrin dual agonist ZP3022 causes a sustained improvement in glycemic control accompanied by an increase in β-cell mass, increased proliferation, and increased mean islet mass. The results highlight that the GLP-1-gastrin dual agonist increases β-cell mass more than liraglutide and that dual agonists could potentially be developed into a new class of antidiabetic treatments.

  14. Molecular and functional characterization of cionin receptors in the ascidian, Ciona intestinalis: the evolutionary origin of the vertebrate cholecystokinin/gastrin family.

    PubMed

    Sekiguchi, Toshio; Ogasawara, Michio; Satake, Honoo

    2012-04-01

    Cholecystokinin (CCK) and gastrin are vertebrate brain-gut peptides featured by a sulfated tyrosine residue and a C-terminally amidated tetrapeptide consensus sequence. Cionin, identified in the ascidian, Ciona intestinalis, the closest species to vertebrates, harbors two sulfated tyrosines and the CCK/gastrin consensus tetrapeptide sequence. While a putative cionin receptor, cior, was cloned, the ligand-receptor relationship between cionin and CioR remains unidentified. Here, we identify two cionin receptors, CioR1 and CioR2, which are the aforementioned putative cionin receptor and its novel paralog respectively. Phylogenetic analysis revealed that CioRs are homologous to vertebrate CCK receptors (CCKRs) and diverged from a common ancestor in the Ciona-specific lineage. Cionin activates intracellular calcium mobilization in cultured cells expressing CioR1 or CioR2. Monosulfated and nonsulfated cionin exhibited less potent or no activity, indicating that CioRs possess pharmacological features similar to the vertebrate CCK-specific receptor CCK1R, rather than its subtype CCK2R, given that a sulfated tyrosine in CCK is required for binding to CCK1R, but not to CCK2R. Collectively, the present data reveal that CioRs share a common ancestor with vertebrate CCKRs and indicate that CCK and CCK1R form the ancestral ligand-receptor pair in the vertebrate CCK/gastrin system. Cionin is expressed in the neural complex, digestive organs, oral siphon and atrial siphons, whereas the expression of ciors was detected mainly in these tissues and the ovary. Furthermore, cioninergic neurons innervate both of the siphons. These results suggest that cionin is involved in the regulation of siphonal functions.

  15. Hormones and Cancer

    PubMed Central

    Blackstein, Martin Elliot

    1984-01-01

    Hormonal therapy is the first systemic therapy to have been used successfully in the treatment of cancer. Developments in steroid hormone receptor assays in the last decade have resulted in the first predictable assays for cancer therapy. The role of hormones, in both the development and treatment of breast, prostate and uterine cancer, is reviewed. Because hormonal therapy is generally a less toxic palliative treatment than other treatments (e.g., chemotherapy and radiation), it has been used for malignancies such as malignant melanoma, hypernephroma, and carcinoid. PMID:21278945

  16. Aging changes in hormone production

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...

  17. Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 And PET

    PubMed Central

    Stoykow, Christian; Erbes, Thalia; Maecke, Helmut R; Bulla, Stefan; Bartholomä, Mark; Mayer, Sebastian; Drendel, Vanessa; Bronsert, Peter; Werner, Martin; Gitsch, Gerald; Weber, Wolfgang A; Stickeler, Elmar; Meyer, Philipp T

    2016-01-01

    Introduction: The gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer. The present study evaluates GRPR imaging as a novel imaging modality in breast cancer by employing positron emission tomography (PET) and the GRPR antagonist 68Ga-RM2. Methods: Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent 68Ga-RM2-PET/CT for pretreatment staging. In vivo tumor uptake of 68Ga-RM2 was correlated with estrogen (ER) and progesterone (PR) receptor expression, HER2/neu status and MIB-1 proliferation index in breast core biopsy specimens. Results: 13/18 tumors demonstrated strongly increased 68Ga-RM2 uptake compared to normal breast tissue (defined as PET-positive). All PET-positive primary tumors were ER- and PR-positive (13/13) in contrast to only 1/5 PET-negative tumors. Mean SUVMAX of ER-positive tumors was 10.6±6.0 compared to 2.3±1.0 in ER-negative tumors (p=0.016). In a multivariate analysis including ER, PR, HER2/neu and MIB-1, only ER expression predicted 68Ga-RM2 uptake (model: r2=0.55, p=0.025). Normal breast tissue showed inter- and intraindividually variable, moderate GRPR binding (SUVMAX 2.3±1.0), while physiological uptake of other organs was considerably less except pancreas. Of note, 68Ga-RM2-PET/CT detected internal mammary lymph nodes with high 68Ga-RM2 uptake (n=8), a contralateral axillary lymph node metastasis (verified by biopsy) and bone metastases (n=1; not detected by bone scan and CT). Conclusion: Our study demonstrates that 68Ga-RM2-PET/CT is a promising imaging method in ER-positive breast cancer. In vivo GRPR binding assessed by 68Ga-RM2-PET/CT correlated with ER expression in primary tumors of untreated patients. PMID:27446498

  18. Bioidentical Hormones and Menopause

    MedlinePlus

    ... made products. These are made in a compounding pharmacy(a pharmacy that mixes medications according to a doctor’s instructions). ... that bioidentical hormones, whether prepared by a compounding pharmacy or pharmaceutical company, are safer to use than ...

  19. Bioidentical Hormones and Menopause

    MedlinePlus

    ... made products. These are made in a compounding pharmacy (a pharmacy that mixes medications according to a doctor’s instructions). ... that bioidentical hormones, whether prepared by a compounding pharmacy or pharmaceutical company, are safer to use than ...

  20. Menopause and Hormones

    MedlinePlus

    ... the participating organizations that have assisted in its reproduction and distribution. Learn More about Menopause and Hormones ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  1. Vaginal bleeding - hormonal

    MedlinePlus

    ... abnormal uterine bleeding is caused by a hormone imbalance. DUB is more common in teenagers or in women who are approaching menopause. DUB is unpredictable. The bleeding may be very heavy or light and can occur often or randomly.

  2. Growth hormone test

    MedlinePlus

    ... under the skin) Infection (a slight risk any time the skin is broken) Alternative Names GH test Images Growth hormone stimulation test - series References Ali O. Hyperpituitarism, tall stature, and overgrowth ...

  3. Thyroid Stimulating Hormone Receptor.

    PubMed

    Tuncel, Murat

    2016-01-05

    Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  4. Thyroid Stimulating Hormone Receptor

    PubMed Central

    Tuncel, Murat

    2017-01-01

    Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases. PMID:28117293

  5. Protein Hormones and Immunity‡

    PubMed Central

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  6. Growth Hormone-Releasing Hormone in Diabetes

    PubMed Central

    Fridlyand, Leonid E.; Tamarina, Natalia A.; Schally, Andrew V.; Philipson, Louis H.

    2016-01-01

    Growth hormone-releasing hormone (GHRH) is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition, GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR) has been demonstrated in different peripheral tissues and cell types, including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggest that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications. PMID:27777568

  7. Fetal organ growth in response to oesophageal infusion of amniotic fluid, colostrum, milk or gastrin-releasing peptide: a study in fetal sheep.

    PubMed

    Trahair, J F; Sangild, P T

    2000-01-01

    The hypothesis of the present study was that the infusion of the biological fluids to which the developing gut is normally exposed (i.e. amniotic fluid, colostrum, milk) and a single growth factor (gastrin-releasing peptide), which is found in high concentrations in fetal fluids and milk, could ameliorate the altered growth induced by the elimination of swallowed input secondary to ligation of the oesophagus. At 108-110 days of gestation the fetal oesophagus was ligated and a catheter inserted towards the stomach (32 fetuses). At 117-119 days of gestation saline (n = 5), amniotic fluid (n = 5), colostral whey (n = 5), milk whey (n = 5) or gastrin-releasing peptide (3.6 nmol day(-1), n = 6), was infused for 7 days (4 x 20 mL day(-1)), or no infusion was given (ligated group, n = 6). A further 15 fetuses were not ligated (normal group, n = 15). All fetuses had carotid artery and/or jugular vein catheters implanted. At 124-126 days of gestation the fetus was delivered and fetal body and organ weights recorded. Analysing the results by ANOVA, there were no effects of either ligation alone or infusion after ligation on fetal weight, crown-rump length, or weight relative to bodyweight of heart, adrenal, pancreas, large intestine and cecum. There were significant differences between the infusion groups for lungs, kidney, pancreas, total gut, abomasum, small intestine, spleen, chest and neck thymus, and mesenteric lymph nodes. Ligation alone significantly reduced small intestinal growth and increased kidney and spleen growth. Colostrum infusion enhanced growth of most organs. Gastrin-releasing peptide significantly increased growth of all the immune organs studied. It was concluded that at an age when premature delivery could be encountered, the fetal gut is capable of significant adaptive growth, to varying degrees, depending on the enteral diet. Growth effects in organs distant to the gut suggest that either gastrointestinal uptake and transport of growth factors or

  8. Facile solid-phase synthesis of sulfated tyrosine-containing peptides: total synthesis of human big gastrin-II and cholecystokinin (CCK)-39.

    PubMed

    Kitagawa, K; Aida, C; Fujiwara, H; Yagami, T; Futaki, S; Kogire, M; Ida, J; Inoue, K

    2001-01-12

    Chemical synthesis of tyrosine O-sulfated peptides is still a laborious task for peptide chemists because of the intrinsic acid-lability of the sulfate moiety. An efficient cleavage/deprotection procedure without loss of the sulfate is the critical difficulty remaining to be solved for fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase synthesis of sulfated peptides. To overcome the difficulty, TFA-mediated solvolysis rates of a tyrosine O-sulfate [Tyr(SO3H)] residue and two protecting groups, tBu for the hydroxyl group of Ser and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) for the guanidino group of Arg, were examined in detail. The desulfation obeyed first-order kinetics with a large entropy (59.6 J.K-1.mol-1) and enthalpy (110.5 kJ.mol-1) of activation. These values substantiated that the desulfation rate of the rigidly solvated Tyr(SO3H) residue was strongly temperature-dependent. By contrast, the SN1-type deprotections were less temperature-dependent and proceeded smoothly in TFA of a high ionizing power. Based on the large rate difference between the desulfation and the SN1-type deprotections in cold TFA, an efficient deprotection protocol for the sulfated peptides was developed. Our synthetic strategy for Tyr(SO3H)-containing peptides with this effective deprotection protocol is as follows: (i) a sulfated peptide chain is directly constructed on 2-chlorotrityl resin with Fmoc-based solid-phase chemistry using Fmoc-Tyr(SO3Na)-OH as a building block; (ii) the protected peptide-resin is treated with 90% aqueous TFA at 0 degree C for an appropriate period of time for the cleavage and deprotection. Human cholecystokinin (CCK)-12, mini gastrin-II (14 residues), and little gastrin-II (17 residues) were synthesized with this method in 26-38% yields without any difficulties. This method was further applied to the stepwise synthesis of human big gastrin-II (34 residues), CCK-33 and -39. Despite the prolonged acid treatment (15-18 h at 0 degree C), the

  9. Plant peptide hormone signalling.

    PubMed

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.

  10. Hormonal control of euryhalinity

    USGS Publications Warehouse

    Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  11. Thyroid hormone transporter defects.

    PubMed

    Grüters, Annette

    2007-01-01

    In in vitro experiments, active transport of thyroid hormones had been repeatedly demonstrated. The membrane transporters for thyroid hormones which have been identified include the organic anion transporting polypeptide, heterodimeric amino acid transporters and the monocarboxylate transporters (MCT) which are the focus of this chapter. The gene encoding MCT8 which was identified as a specific thyroid hormone transporter is located on chromosome Xq13.2. The expression pattern of MCT8 indicates that MCT8 plays an important role in the development of the central nervous system by transporting thyroid hormone into neurons as its main target cells. Mutational analysis of the MCT8 gene revealed mutations or deletions in the MCT8 gene in unrelated male patients with severe psychomotor retardation and biochemical findings consistent with thyroid hormone resistance. Indeed, thyroid function tests in patients with MCT8 mutations demonstrated marked elevations of serum T3 (in the thyrotoxic range), a significant decrease in serum T4 or fT4 and normal to elevated TSH levels.

  12. Male hormonal contraceptives.

    PubMed

    Amory, J K

    2006-06-01

    Efforts are underway to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves the administration of exogenous testosterone (T). When administered to a man, T functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for spermatogenesis. After 2-3 months of treatment, low levels of these gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. Hormonal contraception with exogenous T has proven to be free from serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when the exogenous T is discontinued. Thus, male hormonal is safe, effective and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this recent studies have combined T with progestogens and/or gonadotropin-releasing antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of T and progestogens completely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable T, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.

  13. [Growth hormone signaling pathways].

    PubMed

    Zych, Sławomir; Szatkowska, Iwona; Czerniawska-Piatkowska, Ewa

    2006-01-01

    The substantial improvement in the studies on a very complicated mechanism-- growth hormone signaling in a cell, has been noted in last decade. GH-induced signaling is characterized by activation of several pathways, including extracellular signal-regulated kinase (ERK), the signal transducer and activator of transcription and phosphatidylinositol-3 kinase (PI3) pathways. This review shows a current model of the growth hormone receptor dimerization, rotation of subunits and JAK2 kinase activation as the initial steps in the cascade of events. In the next stages of the signaling process, the GH-(GHR)2-(JAK2)2 complex may activate signaling molecules such as Stat, IRS-1 and IRS-2, and particularly all cascade proteins that activate MAP kinase. These pathways regulate basal cellular functions including target gene transcription, enzymatic activity and metabolite transport. Therefore growth hormone is considered as a major regulator of postnatal growth and metabolism, probably for mammary gland growth and development too.

  14. [Hormonal perturbations in fibromyalgia].

    PubMed

    Schlienger, J L; Perrin, A E; Grunenberger, F; Goichot, B

    2001-12-01

    Fibromyalgia is a syndrome characterized by chronic musculoskeletal pain and fatigue without biological detectable disturbances. The mechanisms of this disease are unknown. It has been postulated that it can be the consequence of a chronic stress mediated mainly through the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system. These fields have been extensively studied. Results were scattered and non convincing. A reduction of growth hormone and IGF-1 levels described in a third of patients has led to a double blind random clinical trial with biogenetic growth hormone. Results were equivocal . Other hormonal systems are grossly normals and circadian rhythms are unaltered. Despite some arguments in favour of a CRH neurons hyperactivity, these results are not able to consolide a particular physiopathological mechanism and to argument for a new therapeutic approach. Many of the abnormalities may be the consequence of psychological disturbances.

  15. Genetics Home Reference: isolated growth hormone deficiency

    MedlinePlus

    ... Isolated growth hormone deficiency Educational Resources (10 links) Boston Children's Hospital CLIMB: Growth Hormone Deficiency Information Sheet (PDF) Disease InfoSearch: Isolated growth hormone deficiency ...

  16. Growth Hormone Deficiency in Adults

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Clinical Trials Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  17. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  18. SHBG (Sex Hormone Binding Globulin)

    MedlinePlus

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  19. Training-overtraining: performance, and hormone levels, after a defined increase in training volume versus intensity in experienced middle- and long-distance runners.

    PubMed

    Lehmann, M; Gastmann, U; Petersen, K G; Bachl, N; Seidel, A; Khalaf, A N; Fischer, S; Keul, J

    1992-12-01

    Performance and hormones were determined in eight middle- and nine long-distance runners after an increase in training volume (ITV, February 1989) or intensity (ITI, February 1990). Seven runners participated in both studies. The objective was to cause an overtraining syndrome. The mean training volume of 85.9 km week-1 increased within 3 weeks to 176.6 km week-1 during ITV and 96-98% of training volume was performed as long-distance runs at mean(s.d.) 67(8)% of maximum capacity. Speed endurance, high-speed and interval runs averaging 9 km week-1 increased within 3 weeks to 22.7 km during ITI, and the total volume increased from 61.6 to 84.7 km. A plateau in endurance performance and decrease in maximum performance occurred during ITV, probably due to overtraining, with performance incompetence over months. Nocturnal catecholamine excretion decreased markedly (47-53%), contrary to exercise-related plasma catecholamine responses, which increased. Resting and exercise-related cortisol and aldosterone levels decreased. Improvement in endurance and maximum performance occurred during ITI indicating a failure to cause an overtraining syndrome in ITI. Decrease in noctural catecholamine excretion was clearly lower (9-26%), exercise-related catecholamine responses showed a significant decrease, cortisol and aldosterone levels remained almost constant, exercise-related prolactin levels decreased slightly. There were no differences in insulin, C-peptide, free testosterone, somatotropic hormone (STH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), tri-iodothyronine (T3) and thyroxine (T4). The decrease in nocturnal catecholamine excretion during ITV might indicate a decrease in intrinsic sympathetic activity in exhausted sportsmen. But it remains open whether this reflected a central nervous system incompetence.

  20. Hormone Profiling in Plant Tissues.

    PubMed

    Müller, Maren; Munné-Bosch, Sergi

    2017-01-01

    Plant hormones are for a long time known to act as chemical messengers in the regulation of physiological processes during a plant's life cycle, from germination to senescence. Furthermore, plant hormones simultaneously coordinate physiological responses to biotic and abiotic stresses. To study the hormonal regulation of physiological processes, three main approaches have been used (1) exogenous application of hormones, (2) correlative studies through measurements of endogenous hormone levels, and (3) use of transgenic and/or mutant plants altered in hormone metabolism or signaling. A plant hormone profiling method is useful to unravel cross talk between hormones and help unravel the hormonal regulation of physiological processes in studies using any of the aforementioned approaches. However, hormone profiling is still particularly challenging due to their very low abundance in plant tissues. In this chapter, a sensitive, rapid, and accurate method to quantify all the five "classic" classes of plant hormones plus other plant growth regulators, such as jasmonates, salicylic acid, melatonin, and brassinosteroids is described. The method includes a fast and simple extraction procedure without time consuming steps as purification or derivatization, followed by optimized ultrahigh-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS) analysis. This protocol facilitates the high-throughput analysis of hormone profiling and is applicable to different plant tissues.

  1. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  2. Cleavage of arginyl-arginine and lysyl-arginine from the C-terminus of pro-hormone peptides by human germinal angiotensin I-converting enzyme (ACE) and the C-domain of human somatic ACE.

    PubMed Central

    Isaac, R E; Williams, T A; Sajid, M; Corvol, P; Coates, D

    1997-01-01

    Mammalian germinal angiotensin I-converting enzyme (gACE) is a single-domain dipeptidyl carboxypeptidase found exclusively in male germ cells, which has almost identical sequence and enzymic properties with the C-domain of the two-domain somatic ACE. Mutant mice that do not express gACE are infertile, suggesting a role for the enzyme in the processing of undefined peptides involved in fertilization. A number of spermatid peptides [e.g. cholecystokinin (CCK) and gastrin] are processed from pro-hormones by endo- and exo-proteolytic cleavages which might generate substrates for gACE. We have shown that peptide hormone intermediates with Lys/Arg-Arg at the C-terminus are high-affinity substrates for human gACE. gACE from human sperm cleaved Arg-Arg from the C-terminus of the CCK5-GRR (GWMDFGRR), a peptide corresponding to the C-terminus of a CCK-gastrin prohormone intermediate. Hydrolysis of CCK5-GRR by recombinant human C-domain ACE was Cl- dependent, with maximal activity achieved in 5-10 mM NaCl at pH 6.4. C-Domain ACE cleaved Lys/Arg-Arg from the C-terminus of dynorphin-(1-7), a pro-TRH peptide KRQHPGKR, and two insect peptides FSPRLGKR and FSPRLGRR. C-Domain ACE displayed high affinity towards all these substrates with Vmax/Km values between 14 and 113 times greater than the Vmax/Km for the conversion of the best known ACE substrate, angiotensin I, into angiotensin II. In conclusion, we have identified a new class of substrates for human gACE, and we suggest that gACE might be an alternative to carboxypeptidase E for the trimming of basic dipeptides from the C-terminus of intermediates generated from pro-hormones by subtilisin-like convertases in human male germ cells. PMID:9371719

  3. A Morphometric Study of Antral G-Cell Density in a Sample of Adult General Population: Comparison of Three Different Methods and Correlation with Patient Demography, Helicobacter pylori Infection, Histomorphology and Circulating Gastrin Levels

    PubMed Central

    Petersson, Fredrik; Borch, Kurt; Rehfeld, Jens F; Franzén, Lennart E

    2009-01-01

    Helicobacter pylori infection has been linked to hypergastrinemia and either decreased or normal G-cell content in the antral mucosa. To clarify this controversial issue, we quantitatively determined antral G-cell content on the same biopsy specimens with three different methods and examined whether these methods are intercorrelated and the relation of these methods to plasma gastrin concentrations, demography, the occurrence of H. pylori infection and chronic gastritis. Gastric antral mucosal biopsy sections from 273 adults (188 with and 85 without H pylori infection) from a general population sample were examined immunohistochemically for G-cells using cell counting, stereology (point counting) and computerized image analysis. Gastritis was scored according to the updated Sydney system. Basal plasma gastrin concentrations were measured by radioimmunoassay. The three methods for G-cell quantification were poorly correlated and the results showed no correlation with basal plasma gastrin concentrations. The antral G-cell density and scores for H. pylori colonization were positively related to age. Neither the scores for chronic inflammation, nor the scores for inflammatory activity, atrophy or intestinal metaplasia were consistently related to the antral G-cell content. In conclusion, the results of three techniques for G-cell quantification in the gastric antral mucosa were poorly intercorrelated and none of the methods correlated with plasma gastrin concentrations. Age and scores for H pylori colonization seem to be determinants of the G-cell density. That common morphometric techniques correlate poorly is of utmost importance to bear in mind when quantitative morphological studies are planned, compared or interpreted. PMID:19079618

  4. The wound hormone jasmonate

    PubMed Central

    Koo, Abraham J.K.; Howe, Gregg A.

    2009-01-01

    Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these threats relies on complex signal transduction networks that link damage-associated signals to appropriate changes in metabolism, growth, and development. Many of these wound-induced adaptive responses are triggered by de novo synthesis of the plant hormone jasmonate (JA). Recent studies provide evidence that JA mediates systemic wound responses through distinct cell autonomous and nonautonomous pathways. In both pathways, bioactive JAs are recognized by an F-box protein-based receptor system that couples hormone binding to ubiquitin-dependent degradation of transcriptional repressor proteins. These results provide a new framework for understanding how plants recognize and respond to tissue injury. PMID:19695649

  5. Sex hormones and acne.

    PubMed

    Ju, Qiang; Tao, Tao; Hu, Tingting; Karadağ, Ayşe Serap; Al-Khuzaei, Safaa; Chen, WenChieh

    The skin is an endocrine organ with the expression of metabolizing enzymes and hormone receptors for diverse hormones. The sebaceous gland is the main site of hormone biosynthesis, especially for androgens, and acne is the classical androgen-mediated dermatosis. In sebocytes, conversion of 17-hydroxyprogesterone directly to dihydrotestosterone bypassing testosterone has been demonstrated, while type II 17β-hydroxysteroid dehydrogenase can inactivate the action of testosterone and dihydrotestosterone. The androgen receptor-dependent genomic effect of dihydrotestosterone on sebocytes is confirmed. Further evidence supports the PI3 K/Akt/FoxO1/mTOR signaling in the involvement of the interplay between androgens, insulin, insulin-like growth factor, and hyperglycemic diet in acne. Androgens not only regulate embryology and lipogenesis/sebum synthesis in sebocytes but also influence inflammation in acne. Genetic studies indicate that regulation of the androgen receptor is an important factor in severe acne. Further studies are required to understand the effect of estrogen and progesterone on sebaceous gland and comedogenesis, considering the change of acne in pregnancy and postmenopausal acne. Special attention should be paid to nonobese patients with polycystic ovarian syndrome and hyperandrogenism-insulin resistance-acanthosis nigricans syndrome. In spite of extensive gynecologic experience in the use of combined oral contraceptives for acne, evidence based on dermatologic observation should be intensified.

  6. [Acne and hormones].

    PubMed

    Faure, Michel

    2002-04-15

    Androgens stimulate sebum production which is necessary for the development of acne. Acne in women may thus be considered as a manifestation of cutaneous androgenization. Most of acnes may be related to an idiopathic skin hyperandrogenism due to in situ enzyme activity and androgen receptor hypersensitivity, as also noted in idiopathic hirsutism. Some acne may correspond to elevated ovarian or adrenal androgen secretion. The presence of acne in women may lead to a diagnosis of functional hyperandrogenism, either polycysticovary syndrome or nonclassical 21-hydroxylase deficiency. Plasma level assays for testosterone, delta 4 androstenedione and 17-OH progesterone and ovarian echography are necessary to determine the possibility for an ovarian or adrenal hyperandrogenism, but not to better treat acne. The goal of hormonal therapy in acne is to oppose the effects of androgens on the sebaceous gland. Hormones may be used in female acne in the absence of endocrine abnormalities. Antiandrogens (cyproterone acetate or aldactone) may be useful in severe acne, hormonal contraceptives with cyproterone acetate or non androgenic progestins in mild or common acne often in association with other anti-acneic drugs. Glucocorticoids have to be administered in acne fulminans and other forms of acute, severe, inflammatory acne, for their anti-inflammatory properties.

  7. Intravenous infusion of gastrin-releasing peptide-27 and bombesin in rats reveals differential effects on meal size and intermeal interval length.

    PubMed

    Washington, Martha C; Salyer, Sarah; Aglan, Amnah H; Sayegh, Ayman I

    2014-01-01

    We have previously shown that the intraperitoneal (i.p.) administration of gastrin-releasing peptide-27 (GRP-27) or bombesin (BN) (at 0.21, 0.41 and 1.03nmol/kg) reduces meal size (MS) and prolongs the intermeal interval (IMI). Here, we hypothesized that the intravenous (i.v.) administration of the same doses of GRP-27 and BN will be as effective as the i.p. administration in evoking these feeding responses. To test this hypothesis, we administered GRP-27 and BN i.v. and measured first MS (10% sucrose), IMI, satiety ratio (SR, IMI/MS) and second MS in overnight food-deprived but not water-deprived male Sprague Dawley rats. We found that (1) only GRP-27 reduced the first MS, (2) BN prolonged the IMI, (3) GRP-27 and BN increased the SR and (4) only BN reduced the size of the second meal. Contrary to our hypothesis, the i.v. administration of GRP-27 and BN affected the MS and IMI differently than did the i.p. administration. In conclusion, this pharmacological study suggests that the MS and IMI are regulated at different sites.

  8. Gastrin-releasing peptide receptor antagonist or N-acetylcysteine combined with omeprazol protect against mitochondrial complex II inhibition in a rat model of gastritis.

    PubMed

    Rezin, Gislaine T; Petronilho, Fabricia C; Araújo, João H; Gonçalves, Cinara L; Daufenbach, Juliana F; Cardoso, Mariane R; Roesler, Rafael; Schwartsmann, Gilberto; Dal-Pizzol, Felipe; Streck, Emilio L

    2011-03-01

    The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis.

  9. Intravenous infusion of gastrin-releasing peptide-27 and bombesin in rats reveals differential effects on meal size and intermeal interval length

    PubMed Central

    Washington, Martha C.; Salyer, Sarah; Aglan, Amnah H.; Sayegh, Ayman I.

    2016-01-01

    We have previously shown that the intraperitoneal (i.p) administration of gastrin-releasing peptide-27 (GRP-27) or bombesin (BN) (at 0.21, 0.41 and 1.03 nmol/kg) reduces meal size (MS) and prolongs the intermeal interval (IMI). Here, we hypothesized that the intravenous (i.v) administration of the same doses of GRP-27 and BN will be as effective as the i.p administration in evoking these feeding responses. To test this hypothesis, we administered GRP-27 and BN i.v and measured first MS (10% sucrose), IMI, satiety ratio (SR, IMI/MS) and second MS in overnight food-deprived but not water-deprived male Sprague Dawley rats. We found that (1) only GRP-27 reduced the first MS, (2) BN prolonged the IMI, (3) GRP-27 and BN increased the SR and (4) only BN reduced the size of the second meal. Contrary to our hypothesis, the i.v administration of GRP-27 and BN affected the MS and IMI differently than did the i.p administration. In conclusion, this pharmacological study suggests that the MS and IMI are regulated at different sites. PMID:24291388

  10. Stereochemistry of amino acid spacers determines the pharmacokinetics of (111)In-DOTA-minigastrin analogues for targeting the CCK2/gastrin receptor.

    PubMed

    Kolenc Peitl, Petra; Tamma, MariaLuisa; Kroselj, Marko; Braun, Friederike; Waser, Beatrice; Reubi, Jean Claude; Sollner Dolenc, Marija; Maecke, Helmut R; Mansi, Rosalba

    2015-06-17

    The metabolic instability and high kidney retention of minigastrin (MG) analogues hamper their suitability for use in peptide-receptor radionuclide therapy of CCK2/gastrin receptor-expressing tumors. High kidney retention has been related to N-terminal glutamic acids and can be substantially reduced by coinjection of polyglutamic acids or gelofusine. The aim of the present study was to investigate the influence of the stereochemistry of the N-terminal amino acid spacer on the enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-L). Using circular dichroism measurements, we demonstrate the important role of secondary structure on the pharmacokinetics of the two MG analogues. The higher in vitro serum stability together with the improved tumor-to-kidney ratio of the (d-Glu)6 congener indicates that this MG analogue might be a good candidate for further clinical study.

  11. Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

    PubMed Central

    Gutierrez-Mecinas, Maria; Polgár, Erika; Todd, Andrew J

    2016-01-01

    Background Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway. PMID:27270268

  12. A role for glucocorticoid-signaling in depression-like behavior of gastrin-releasing peptide receptor knock-out mice.

    PubMed

    Monje, Francisco J; Kim, Eun-Jung; Cabatic, Maureen; Lubec, Gert; Herkner, Kurt R; Pollak, Daniela D

    2011-08-01

    Abstract Background. The gastrin-releasing peptide receptor (GRPR) is highly expressed in the limbic system, where it importantly regulates emotional functions and in the suprachiasmatic nucleus, where it is central for the photic resetting of the circadian clock. Mice lacking GRPR presented with deficient light-induced phase shift in activity as well altered emotional learning and amygdala function. The effect of GRPR deletion on depression-like behavior and its molecular signature in the amygdala, however, has not yet been evaluated. Methods. GRPR knock-out mice (GRPR-KO) were tested in the forced-swim test and the sucrose preference test for depression-like behavior. Gene expression in the basolateral nucleus of the amygdala was evaluated by micorarray analysis subsequent to laser-capture microdissection-assisted extraction of mRNA. The expression of selected genes was confirmed by RT-PCR. Results. GRPR-KO mice were found to present with increased depression-like behavior. Microarray analysis revealed down-regulation of several glucocorticoid-responsive genes in the basolateral amygdala. Acute administration of dexamethasone reversed the behavioral phenotype and alterations in gene expression. Discussion. We propose that deletion of GRPR leads to the induction of depression-like behavior which is paralleled by dysregulation of amygdala gene expression, potentially resulting from deficient light-induced corticosterone release in GRPR-KO.

  13. Comparative Anatomy of Gastrin-releasing Peptide Pathways in the Trigeminal Sensory System of Mouse and the Asian House Musk Shrew Suncus murinus

    PubMed Central

    Takanami, Keiko; Inoue, Kaihei; Mukai, Hiroki; Tamura, Kei; Jogahara, Takamichi; Oda, Sen-ichi; Kawata, Mitsuhiro; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2016-01-01

    Gastrin-releasing peptide (GRP) has recently been identified as an itch-signaling molecule in the primary afferents and spinal cord of rodents. However, little information exists on the expression and localization of GRP in the trigeminal somatosensory system other than in rats. We examined the generality of the trigeminal GRP system in mammals using two distinct species, suncus as a model of specialized placental mammals known to have a well-developed trigeminal sensory system and mice as a representative small laboratory animal. We first analyzed the gross morphology of the trigeminal somatosensory system in suncus to provide a brainstem atlas on which to map GRP distribution. Immunohistochemical analyses showed that 8% of trigeminal ganglion neurons in suncus and 6% in mice expressed GRP. Expression was restricted to cells with smaller somata. The GRP-containing fibers were densely distributed in the superficial layers of the caudal part of the trigeminal spinal nucleus (Vc) but rare in the rostral parts, both in suncus and mice. Expression of GRP receptor mRNA and protein was also detected in the Vc of suncus. Taken together, these results suggest that the trigeminal GRP system mediating itch sensation is conserved in mammals. PMID:28127106

  14. Thyroid Hormones and Methylmercury Toxicity

    PubMed Central

    O’Mara, Daniel M.; Aschner, Michael

    2013-01-01

    Thyroid hormones are essential for cellular metabolism, growth, and development. In particular, an adequate supply of thyroid hormones is critical for fetal neurodevelopment. Thyroid hormone tissue activation and inactivation in brain, liver, and other tissues is controlled by the deiodinases through the removal of iodine atoms. Selenium, an essential element critical for deiodinase activity, is sensitive to mercury and, therefore, when its availability is reduced, brain development might be altered. This review addresses the possibility that high exposures to the organometal, methylmercury (MeHg), may perturb neurodevelopmental processes by selectively affecting thyroid hormone homeostasis and function. PMID:18716716

  15. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    PubMed

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  16. Identification and characterization of gastrointestinal hormone immunoreactive cells in the skin and parotoids of Chinese toad Bufo gargarizans.

    PubMed

    Wang, Huan; Wu, Yuan-Yuan; Zhang, Rui; Zhu, Xue; Zhang, Sheng-Zhou

    2014-01-01

    The skin and skin secretion of Chinese toad Bufo gargarizans have long been used in traditional Chinese medicine. However, the exact types and location of bioactive substances in Bufo gargarizans skin still have not been fully elucidated. The aim of the study was to investigate the distribution and density of six types of gastrointestinal (GI) hormone immunoreactive (IR) cells in the skin and parotoids of Bufo gargarizans. Immunohistochemistry was used for qualitative and semiquantitative analysis of GI hormone presence in the dorsal and ventral skin, and parotoids of eight adult Chinese toads. Six types of IR cells were found: serotonin (5-HT), glucagon (GLU), gastrin (GAS), somatostatin (SS), pancreatic polypeptide (PP) and neuropeptide Y(NPY) IR cells. They were mainly present in the epidermis and skin glands. 5-HT-IR cells were distributed in all layers of epidermis and glands, with higher density in the glands. Glucagon was prominently expressed in the epidermis and the bottle-shaped glands of parotoids; however, it was not present in the granular glands of skin and parotoids. The distributions of GAS and SS-IR cells were similar since they were present mainly in mucous, granular and bottle-shaped glands, while these cell types were absent in the differentiated glands of parotoids. PP-IR cells were predominant in the granular glands and the bottle-shaped glands. The expression of NPY was high in epidermal stratum granulosum and mucous glands of the dorsal skin, the bottle-shaped glands and differentiated glands of parotoids, while NPY-IR was rarely seen in the granular glands of ventral skin, and not present in the granular glands of dorsal skin and parotoids. The expression of several types of GI hormones in the skin and parotoids of Bufo gargarizans varies depending on tissue and type of glands.

  17. Hormonal Programming Across the Lifespan

    PubMed Central

    Tobet, Stuart A; Lara, Hernan E; Lucion, Aldo B; Wilson, Melinda E; Recabarren, Sergio E; Paredes, Alfonso H

    2013-01-01

    Hormones influence countless biological processes across the lifespan, and during developmental sensitive periods hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous critical periods in development wherein different targets are affected. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be a mediator of sexual differentiation of the neonatal brain. During development of the ovary, exposure to excess gonadal hormones leads to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased sympathetic nerve activity and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function. PMID:22700441

  18. Types of Cancer Treatment: Hormone Therapy

    Cancer.gov

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  19. Growth hormone stimulation test - series (image)

    MedlinePlus

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. ... performed on infants and children to identify human growth hormone (hGH) deficiency as a cause of growth retardation. ...

  20. Quo vadis plant hormone analysis?

    PubMed

    Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, Petr; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

    2014-07-01

    Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.

  1. Hormone therapy for transgender patients

    PubMed Central

    2016-01-01

    Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients. Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. PMID:28078219

  2. Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IκB-α/NF-κB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats.

    PubMed

    Long, Lingli; Wang, Jingnan; Chen, Ningning; Zheng, Shuhui; Shi, Lanying; Xu, Yuxia; Luo, Canqiao; Deng, Yubin

    2016-06-01

    The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin's action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-α and interferon-γ by ELISA and radioimmunoassay. The protein levels of NF-κB, p-IκB-α, IκB-α, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpine-treated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpine-treated rats. NF-κB, p-IκB-α, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IκB-α/NF-κB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats.

  3. In Vivo Stabilization of a Gastrin-Releasing Peptide Receptor Antagonist Enhances PET Imaging and Radionuclide Therapy of Prostate Cancer in Preclinical Studies.

    PubMed

    Chatalic, Kristell L S; Konijnenberg, Mark; Nonnekens, Julie; de Blois, Erik; Hoeben, Sander; de Ridder, Corrina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; van Gent, Dik C; Nock, Berthold A; Maina, Theodosia; van Weerden, Wytske M; de Jong, Marion

    2016-01-01

    A single tool for early detection, accurate staging, and personalized treatment of prostate cancer (PCa) would be a major breakthrough in the field of PCa. Gastrin-releasing peptide receptor (GRPR) targeting peptides are promising probes for a theranostic approach for PCa overexpressing GRPR. However, the successful application of small peptides in a theranostic approach is often hampered by their fast in vivo degradation by proteolytic enzymes, such as neutral endopeptidase (NEP). Here we show for the first time that co-injection of a NEP inhibitor (phosphoramidon (PA)) can lead to an impressive enhancement of diagnostic sensitivity and therapeutic efficacy of the theranostic (68)Ga-/(177)Lu-JMV4168 GRPR-antagonist. Co-injection of PA (300 µg) led to stabilization of (177)Lu-JMV4168 in murine peripheral blood. In PC-3 tumor-bearing mice, PA co-injection led to a two-fold increase in tumor uptake of (68)Ga-/(177)Lu-JMV4168, 1 h after injection. In positron emission tomography (PET) imaging with (68)Ga-JMV4168, PA co-injection substantially enhanced PC-3 tumor signal intensity. Radionuclide therapy with (177)Lu-JMV4168 resulted in significant regression of PC-3 tumor size. Radionuclide therapy efficacy was confirmed by production of DNA double strand breaks, decreased cell proliferation and increased apoptosis. Increased survival rates were observed in mice treated with (177)Lu-JMV4168 plus PA as compared to those without PA. This data shows that co-injection of the enzyme inhibitor PA greatly enhances the theranostic potential of GRPR-radioantagonists for future application in PCa patients.

  4. Anti-ulcerogenic mechanisms of the sesquiterpene lactone onopordopicrin-enriched fraction from Arctium lappa L. (Asteraceae): role of somatostatin, gastrin, and endogenous sulfhydryls and nitric oxide.

    PubMed

    de Almeida, Ana Beatriz Albino; Luiz-Ferreira, Anderson; Cola, Maíra; Di Pietro Magri, Luciana; Batista, Leonia Maria; de Paiva, Joseilson Alves; Trigo, José Roberto; Souza-Brito, Alba R M

    2012-04-01

    Arctium lappa L. has been used in folk medicine as a diuretic, depurative, and digestive stimulant and in dermatological conditions. The mechanisms involved in the anti-ulcerogenic activity of the sesquiterpene onopordopicrin (ONP)-enriched fraction (termed the ONP fraction), obtained from A. lappa leaves, were studied. The gastroprotective mechanism of the ONP fraction was evaluated in experimental in vivo models in rodents, mimicking this disease in humans. ONP fraction (50 mg/kg, p.o.) significantly inhibited the mucosal injury induced by ethanol/HCl solution (75%), indomethacin/bethanecol (68.9%), and stress (58.3%). When the ONP fraction was investigated in pylorus ligature, it did not induce alteration in the gastric volume but did modify the pH and total acid concentration of gastric juice. ONP fraction significantly increased serum somatostatin levels (82.1±4.1 vs. control group 12.7±4 pmol/L) and decreased serum gastrin levels (62.6±6.04 vs. control group 361.5±8.2 μU/mL). Mucus production was not significantly altered by the ONP fraction. Gastroprotection by the ONP fraction was completely inhibited by N-ethylmaleimide treatment and did not modify the effect in the animals pretreated with l-N(G)-nitroarginine methyl ester. These results suggest an antisecretory mechanism involved with the antiulcerogenic effect of the ONP fraction. However, only endogenous sulfhydryls play an important role in gastroprotection of the ONP fraction.

  5. Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer

    PubMed Central

    Dalm, Simone U.; Schrijver, Willemijne A. M. E.; Sieuwerts, Anieta M.; Look, Maxime P.; Ziel - van der Made, Angelique C. J.; de Weerd, Vanja; Martens, John W.; van Diest, Paul J.; de Jong, Marion; van Deurzen, Carolien H. M.

    2017-01-01

    Background The gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor-mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC. Methods mRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction. Receptor mRNA expression levels were associated with clinico-pathological factors and expression levels of primary tumors and corresponding metastases were compared. Results Binding of GRPR and SSTR radioligands to tumor tissue correlated significantly with receptor mRNA expression. High GRPR and SSTR2 mRNA levels were associated with estrogen receptor (ESR1)-positive tumors (p<0.001 for both receptors). There was no significant difference in GRPR mRNA expression of primary tumors versus paired metastases. Regarding SSTR2 mRNA expression, there was also no significant difference in the majority of cases, apart from liver and ovarian metastases which showed a significantly lower expression compared to the corresponding primary tumors (p = 0.02 and p = 0.03, respectively). Conclusion Targeting the GRPR and SSTR2 for nuclear imaging and/or treatment has the potential to improve BC care in primary as well as metastatic disease. PMID:28107508

  6. In Vivo Stabilization of a Gastrin-Releasing Peptide Receptor Antagonist Enhances PET Imaging and Radionuclide Therapy of Prostate Cancer in Preclinical Studies

    PubMed Central

    Chatalic, Kristell L.S.; Konijnenberg, Mark; Nonnekens, Julie; de Blois, Erik; Hoeben, Sander; de Ridder, Corrina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; van Gent, Dik C.; Nock, Berthold A.; Maina, Theodosia; van Weerden, Wytske M.; de Jong, Marion

    2016-01-01

    A single tool for early detection, accurate staging, and personalized treatment of prostate cancer (PCa) would be a major breakthrough in the field of PCa. Gastrin-releasing peptide receptor (GRPR) targeting peptides are promising probes for a theranostic approach for PCa overexpressing GRPR. However, the successful application of small peptides in a theranostic approach is often hampered by their fast in vivo degradation by proteolytic enzymes, such as neutral endopeptidase (NEP). Here we show for the first time that co-injection of a NEP inhibitor (phosphoramidon (PA)) can lead to an impressive enhancement of diagnostic sensitivity and therapeutic efficacy of the theranostic 68Ga-/177Lu-JMV4168 GRPR-antagonist. Co-injection of PA (300 µg) led to stabilization of 177Lu-JMV4168 in murine peripheral blood. In PC-3 tumor-bearing mice, PA co-injection led to a two-fold increase in tumor uptake of 68Ga-/177Lu-JMV4168, 1 h after injection. In positron emission tomography (PET) imaging with 68Ga-JMV4168, PA co-injection substantially enhanced PC-3 tumor signal intensity. Radionuclide therapy with 177Lu-JMV4168 resulted in significant regression of PC-3 tumor size. Radionuclide therapy efficacy was confirmed by production of DNA double strand breaks, decreased cell proliferation and increased apoptosis. Increased survival rates were observed in mice treated with 177Lu-JMV4168 plus PA as compared to those without PA. This data shows that co-injection of the enzyme inhibitor PA greatly enhances the theranostic potential of GRPR-radioantagonists for future application in PCa patients. PMID:26722377

  7. Distinct functions of opioid-related peptides and gastrin-releasing peptide in regulating itch and pain in the spinal cord of primates

    PubMed Central

    Lee, Heeseung; Ko, Mei-Chuan

    2015-01-01

    How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, β-endorphin (10–100 nmol) and GRP (1–10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike β-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100–1000 nmol) and nociceptin-orphanin FQ (3–30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1–17) (10–100 nmol) dose-dependently attenuates both β-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by β-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans. PMID:26119696

  8. Early phosphorylation events following the treatment of Swiss 3T3 cells with bombesin and the mammalian bombesin-related peptide, gastrin-releasing peptide.

    PubMed Central

    Isacke, C M; Meisenhelder, J; Brown, K D; Gould, K L; Gould, S J; Hunter, T

    1986-01-01

    Bombesin and the related mammalian peptides, such as gastrin-releasing peptide (GRP), are potent mitogens for some fibroblast cell lines. Here we have examined the bombesin- and GRP-mediated changes in the phosphorylation of proteins in Swiss 3T3 cells and compared these to the events observed after platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and tumor promoter treatment. In agreement with previous reports, bombesin, GRP and PDGF, but not EGF, increased the activity of protein kinase C. This was assayed by an inhibition of [125I]EGF binding, stimulation in phosphorylation of pp60c-src on serine 12 and stimulation in phosphorylation of a group of 80 kd proteins. The different phosphorylated forms of the 80 kd proteins were examined by tryptic peptide mapping and shown to contain multiple phosphorylation sites. An investigation of the tyrosine phosphorylation events following mitogen treatment revealed a significant difference between PDGF and the bombesin peptides. PDGF treatment caused a marked increase in total cellular phosphotyrosine levels, and tyrosine phosphorylation both of known substrates and its own receptor. In contrast, bombesin and GRP treatments resulted in only a weak or undetectable increase in tyrosine phosphorylation of total cellular protein or known substrates. In this respect bombesin and GRP were more similar to EGF. The fact that the bombesin peptides do not induce a phosphorylation response identical with either PDGF or EGF suggests that there is not a single common signal pathway which is activated by all these mitogens. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:2431903

  9. Neuromedin B and gastrin releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong renilla GFP in NPY neurons

    PubMed Central

    van den Pol, Anthony N.; Yao, Yang; Fu, Li-Ying; Foo, Kylie; Huang, Hao; Coppari, Roberto; Lowell, Brad; Broberger, Christian

    2009-01-01

    Neuropeptide Y (NPY) is one of the most widespread neuropeptides in the brain. Transgenic mice were generated that expressed bright renilla GFP in most or all of the known NPY cells in the brain, which otherwise were not identifiable. GFP expression in NPY cells was confirmed with immunocytochemistry and single cell RT-PCR. NPY neurons in the hypothalamic arcuate nucleus play an important role in energy homeostasis and endocrine control. Whole cell patch clamp recording was used to study identified arcuate NPY cells. Primary agents that regulate energy balance include melanocortin receptor agonists, AgRP, and cannabinoids; none of these substances substantially influenced electrical properties of NPY neurons. In striking contrast, neuropeptides of the bombesin family, including gastrin releasing peptide and neuromedin B which are found in axons in the arcuate nucleus and may also be released from the gut to signal the brain, showed strong direct excitatory actions at nanomolar levels on the NPY neurons, stronger than the actions of ghrelin and hypocretin/orexin. Bombesin-related peptides reduced input resistance and depolarized the membrane potential. The depolarization was attenuated by several factors: substitution of choline for sodium, extracellular Ni2+, inclusion of BAPTA in the pipette, KB-R7943 and SKF96365. Reduced extracellular calcium enhanced the current, which reversed around − 20 mV. Together, these data suggest two mechanisms, activation of non-selective cation channels and the sodium/calcium exchanger. Since both NPY and POMC neurons, which we also studied, are similarly directly excited by bombesin-like peptides, the peptides may function to initiate broad activation, rather than the cell-type selective activation or inhibition reported for many other compounds that modulate energy homeostasis. PMID:19357287

  10. Plant hormone signaling lightens up: integrators of light and hormones.

    PubMed

    Lau, On Sun; Deng, Xing Wang

    2010-10-01

    Light is an important environmental signal that regulates diverse growth and developmental processes in plants. In these light-regulated processes, multiple hormonal pathways are often modulated by light to mediate the developmental changes. Conversely, hormone levels in plants also serve as endogenous cues in influencing light responsiveness. Although interactions between light and hormone signaling pathways have long been observed, recent studies have advanced our understanding by identifying signaling integrators that connect the pathways. These integrators, namely PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), PIF4, PIF3-LIKE 5 (PIL5)/PIF1 and LONG HYPOCOTYL 5 (HY5), are key light signaling components and they link light signals to the signaling of phytohormones, such as gibberellin (GA), abscisic acid (ABA), auxin and cytokinin, in regulating seedling photomorphogenesis and seed germination. This review focuses on these integrators in illustrating how light and hormone interact.

  11. Hormone signaling in plant development.

    PubMed

    Durbak, Amanda; Yao, Hong; McSteen, Paula

    2012-02-01

    Hormone signaling plays diverse and critical roles during plant development. In particular, hormone interactions regulate meristem function and therefore control formation of all organs in the plant. Recent advances have dissected commonalities and differences in the interaction of auxin and cytokinin in the regulation of shoot and root apical meristem function. In addition, brassinosteroid hormones have recently been discovered to regulate root apical meristem size. Further insights have also been made into our understanding of the mechanism of crosstalk among auxin, cytokinin, and strigolactone in axillary meristems.

  12. Hormone replacement therapy and longevity.

    PubMed

    Comhaire, F

    2016-02-01

    To assess whether hormone replacement therapy influences longevity, an analysis was made of published life tables allowing for the calculation of the relative benefit of hormone replacement therapy on longevity in men with late onset hypogonadism and in post-menopausal women. It was found that testosterone replacement therapy of men suffering from late onset hypogonadism increased survival rate by 9-10% in 5 years, similar to that of eugonadal, non-LOH men with normal endogenous testosterone secretion. Oestrogen replacement therapy resulted in increased survival by 2.6% in 5 years. It is concluded that hormone replacement therapy increases longevity.

  13. Specific involvement of gonadal hormones in the functional maturation of growth hormone releasing hormone (GHRH) neurons.

    PubMed

    Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G

    2010-12-01

    Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

  14. Steroid hormones and BDNF.

    PubMed

    Pluchino, N; Russo, M; Santoro, A N; Litta, P; Cela, V; Genazzani, A R

    2013-06-03

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.

  15. Calciotropic hormones during reproduction.

    PubMed

    Verhaeghe, J; Bouillon, R

    1992-03-01

    This review summarizes the reported effects of the menstrual cycle, pregnancy and lactation on serum concentration of the calciotropic hormones PTH and 1,25(OH)2D. A midcycle rise in PTH and 1,25(OH)2D has been observed, but in the majority of studies there was no change in PTH and 1,25(OH)2D concentrations throughout the menstrual cycle. Both total and free 1,25(OH)2D levels are increased during pregnancy. The renal 1,25(OH)2D production is stimulated, and there is some evidence of 1,25(OH)2D production by decidua/placenta and fetal kidney in vitro; the decidual/placental production should not be overestimated in vivo. The increased renal 1 alpha-hydroxylase activity is possibly mediated by estrogens and PTH, although the effect of pregnancy on PTH remains uncertain. Increased serum 1,25(OH)2D concentrations probably result in a rise of intestinal calcium absorption during pregnancy. There is a postdelivery drop in PTH and 1,25(OH)2D levels, but they are increased when lactation is prolonged, or in mothers nursing twins. The l alpha-hydroxylase activity during lactation may be stimulated by PTH, but also by prolactin.

  16. Network Identification of Hormonal Regulation

    PubMed Central

    Vis, Daniel J.; Westerhuis, Johan A.; Hoefsloot, Huub C. J.; Roelfsema, Ferdinand; van der Greef, Jan

    2014-01-01

    Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for detecting regulatory relations between hormones. This is demonstrated with a cohort of obese women, who underwent blood sampling at 10 minute intervals for 24-hours. The cohort was treated with bromocriptine in an attempt to clarify how hormone relations change by treatment. The detected regulatory relations are summarized in a network graph and treatment-induced changes in the relations are determined. The proposed method identifies many relations, including well-known ones. Ultimately, the method provides ways to improve the description and understanding of normal hormonal relations and deviations caused by disease or treatment. PMID:24852517

  17. Hormones, Women and Breast Cancer

    MedlinePlus

    ... used therapy is a female hormone blocker called tamoxifen. A newer therapy uses a pill (anastrozole, letrozole, ... are at high risk for developing breast cancer, tamoxifen or raloxifene can also be taken to prevent ...

  18. Hormone therapy for breast cancer

    MedlinePlus

    ... Mood swings Depression Loss of interest in sex Drug Side Effects The side effects of hormone therapy depend on the drug. Common side effects include hot flashes, night sweats, and vaginal dryness . ...

  19. Side Effects of Hormone Therapy

    MedlinePlus

    ... FAQs Why Give to PCF? Featured Blue Jacket Fashion Show Featured Donate Contact Us Menu Close Donate ... Featured Why Give to PCF? Featured Blue Jacket Fashion Show Contact Us Side Effects of Hormone Therapy ...

  20. Ghrelin: much more than a hunger hormone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  1. The evolution of peptide hormones.

    PubMed

    Niall, H D

    1982-01-01

    Despite limitations in our present knowledge it is already possible to discern the main features of peptide hormone evolution, since the same mechanisms (and indeed the same hormone molecules) function in many different ways. This underlying unity of organization has its basis in the tendency of biochemical networks, once established, to survive and diversify. The most surprising recent findings in endocrinology have been the discovery of vertebrate peptide hormones in multiple sites within the same organism, and the reports, persuasive but requiring confirmation, of vertebrate hormones in primitive unicellular organisms (20, 20a). Perhaps the major challenge for the future is to define the roles and interactions of the many peptide hormones identified in brain (18). The most primitive bacteria and the human brain, though an enormous evolutionary distance apart, may have more in common than we have recognized until now. As Axelrod & Hamilton have pointed out in a recent provocative article, "The Evolution of Cooperation" (1), bacteria, though lacking a brain, are capable of adaptive behavior that can be analysed in terms of game theory. It is clear that we can learn a great deal about the whole evolutionary process from a study of the versatile and durable peptide hormones molecules.

  2. Growth hormone signaling pathways.

    PubMed

    Carter-Su, Christin; Schwartz, Jessica; Argetsinger, Lawrence S

    2016-06-01

    Over 20years ago, our laboratory showed that growth hormone (GH) signals through the GH receptor-associated tyrosine kinase JAK2. We showed that GH binding to its membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses. These proteins and pathways include: 1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway; 3) insulin receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and Akt pathway; 4) signal regulatory protein α, a transmembrane scaffold protein that recruits proteins including the tyrosine phosphatase SHP2; and 5) SH2B1, a scaffold protein that can activate JAK2 and enhance GH regulation of the actin cytoskeleton. Our recent work has focused on the function of SH2B1. We have shown that SH2B1β is recruited to and phosphorylated by JAK2 in response to GH. SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found in humans exhibiting severe early-onset childhood obesity and insulin resistance. These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor tyrosine kinases, our results raise the possibility that effects of SH2B1 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight.

  3. Physical and hormonal evaluation of transsexual patients during hormonal therapy.

    PubMed

    Meyer, W J; Finkelstein, J W; Stuart, C A; Webb, A; Smith, E R; Payer, A F; Walker, P A

    1981-08-01

    The optimal hormonal therapy for transsexual patients is not known. The physical and hormonal characteristics of 38 noncastrate male-to-female transsexuals and 14 noncastrate female-to-male transsexuals have been measured before and/or during therapy with various forms and dosages of hormonal therapy. All patients were hormonally and physically normal prior to therapy. Ethinyl estradiol was superior to conjugated estrogen in suppression of testosterone and gonadotropins but equal in effecting breast growth. The changes in physical and hormonal characteristics were the same for 0.1 mg/d and 0.5 mg/d of ethinyl estradiol. The female-to-male transsexuals were well managed with a dose of intramuscular testosterone cypionate of 400 mg/month, usually given 200 mg every two weeks. The maximal clitoral length reached was usually 4 cm. Higher doses of testosterone did not further increase clitoral length or suppression of gonadotropins; lower doses did not suppress the gonadotropins. Based on the information found in this study, we recommend 0.1 mg/d of ethinyl estradiol for the noncastrate male-to-female transsexual and 200 mg of intramuscular testosterone cypionate every two weeks for the noncastrate female-to-male transsexual.

  4. Thyroid Hormone Deiodinases and Cancer

    PubMed Central

    Casula, Sabina; Bianco, Antonio C.

    2012-01-01

    Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches. PMID:22675319

  5. Disorders of antidiuretic hormone.

    PubMed

    Vokes, T J; Robertson, G L

    1988-06-01

    Disorders of thirst and vasopressin secretion present clinically in one of three ways: as hypotonic polyuria (DI), as hypodipsic hyponatremia, and as hyponatremia. In evaluating a patient with DI, the major challenge is to differentiate between primary polydipsia and neurogenic and nephrogenic DI. This is best accomplished through a series of steps that start with simple clinical observation, and progress, as necessary, to more complicated diagnostic procedures (Fig. 1). If the diagnosis is not clear from the clinical setting and the patient's history, the first step is to measure plasma osmolality and sodium under conditions of ad libitum fluid intake. If the results are clearly above the upper limit of normal range, primary polydipsia is excluded and the work-up can proceed directly to administration of vasopressin or DDAVP and/or a measurement of plasma vasopressin levels to differentiate between neurogenic and nephrogenic DI. If basal plasma osmolality and sodium fall within normal range, the standard dehydration test should be performed. If urine osmolality does not increase above that of plasma despite evident dehydration, primary polydipsia is excluded and the effect of vasopressin or DDAVP on urine osmolality should be examined to differentiate between neurogenic and nephrogenic DI. If administration of antidiuretic hormone increases urine osmolality by more than 50 per cent, the patient has severe neurogenic DI. If the increase in urine osmolality is less than 50 per cent, the patient has nephrogenic DI. In patients who do not concentrate urine above that of plasma in response to dehydration, the best approach is to measure plasma vasopressin, osmolality, and sodium after the latter have been increased above normal range by dehydration and/or infusion of hypertonic saline. When these results are plotted on a suitable nomogram (Fig. 2), neurogenic DI can be clearly diagnosed from the relative deficiency of vasopressin. In patients with normal vasopressin

  6. A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth.

    PubMed Central

    Li, K; Nagalla, S R; Spindel, E R

    1994-01-01

    Gastrin-releasing peptide (GRP) is developmentally expressed in human fetal lung and is a growth factor for normal and neoplastic lung but its role in normal lung development has yet to be clearly defined. In this study we have characterized the expression of GRP and its receptor in fetal rhesus monkey lung and determined the effects of bombesin on fetal lung development in vitro. By RNA blot analysis, GRP mRNA was first detectable in fetal monkey lung at 63 days gestation, reached highest levels at 80 days gestation, and then declined to near adult levels by 120 days gestation; a pattern closely paralleling GRP expression in human fetal lung. As in human lung, in situ hybridization localized GRP mRNA to neuroendocrine cells though during the canalicular phase of development (between 63-80 days gestation) GRP mRNA was present not only in classic pulmonary neuroendocrine cells, but also in cells of budding airways. Immunohistochemistry showed that bombesin-like immunoreactivity was present in neuroendocrine cells, but not in budding airways, suggesting that in budding airways either the GRP mRNA is not translated, is rapidly secreted, or a related, but different RNA is present. RNase protection analysis using a probe to the monkey GRP receptor demonstrated that the time course of receptor RNA expression closely paralleled the time course of GRP RNA expression. In situ hybridization showed that GRP receptors were primarily expressed in epithelial cells of the developing airways. Thus GRP would appear to be secreted from neuroendocrine cells to act on target cells in developing airways. This hypothesis was confirmed by organ culture of fetal monkey lung in the presence of bombesin and bombesin antagonists. Bombesin treatment at 1 and 10 nM significantly increased DNA synthesis in airway epithelial cells and significantly increased the number and size of airways in cultured fetal lung. In fact, culturing 60 d fetal lung for 5 d with 10 nM bombesin increased airway size

  7. Luteinizing hormone-releasing hormone agonists in premenopausal hormone receptor-positive breast cancer.

    PubMed

    Tan, Sing-Huang; Wolff, Antonio C

    2007-02-01

    Ovarian function suppression for the treatment of premenopausal breast cancer was first used in the late 19th century. Traditionally, ovarian function suppression had been accomplished irreversibly via irradiation or surgery, but analogues of the luteinizing hormone-releasing hormone (LH-RH) have emerged as reliable and reversible agents for this purpose, especially the LH-RH agonists. Luteinizing hormone-releasing hormone antagonists are in earlier stages of development in breast cancer and are not currently in clinical use. Luteinizing hormonereleasing hormone agonists act by pituitary desensitization and receptor downregulation, thereby suppressing gonadotrophin release. Limited information is available comparing the efficacies of the depot preparations of various agonists, but pharmacodynamic studies have shown comparable suppressive capabilities on estradiol and luteinizing hormone. At present, only monthly goserelin is Food and Drug Administration-approved for the treatment of estrogen receptor-positive, premenopausal metastatic breast cancer in the United States. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in premenopausal advanced breast cancer. They offer similar outcomes compared with tamoxifen, but the endocrine combination appears to be more effective than LH-RH agonists alone. In the adjuvant setting, LH-RH agonists versus no therapy reduce the annual odds of recurrence and death in women aged>50 years with estrogen receptor-positive tumors. Luteinizing hormone-releasing hormone agonists alone or in combination with tamoxifen have shown disease-free survival rates similar to chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil). Outcomes of chemotherapy with or without LH-RH agonists are comparable, though a few trials favor the combination in young premenopausal women (aged<40 years). Adjuvant LH-RH agonists with or without tamoxifen might be as efficacious as tamoxifen alone

  8. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites.

    PubMed Central

    Snyder, G D; Capdevila, J; Chacos, N; Manna, S; Falck, J R

    1983-01-01

    Anterior pituitary cells were incubated in the presence of luteinizing hormone-releasing hormone and one of three inhibitors of arachidonic acid metabolism:indomethacin, an inhibitor of the cyclooxygenase system; nordihydroguaiaretic acid, an antioxidant that inhibits lipoxygenase; and icosatetraynoic acid, an acetylenic analogue of arachidonic acid that blocks all known pathways of arachidonic acid metabolism. Indomethacin was ineffective in blocking luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Nordihydroguaiaretic acid was only marginally capable of inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Icosatetraynoic acid at 10 microM completely inhibited stimulated luteinizing hormone secretion. Addition of several epoxygenated arachidonic acid metabolites to cells in vitro resulted in secretion of luteinizing hormone equal to or greater than that induced by 10 nM luteinizing hormone-releasing hormone. The half-maximal effective dose for these compounds was approximately 50 nM. The 5,6-epoxyicosatrienoic acid was the most potent of the compounds tested. These studies suggest that luteinizing hormone-releasing hormone-stimulated luteinizing hormone release is closely coupled with the production of oxidized arachidonic acid metabolites. Moreover, one or more of the epoxygenated arachidonic acid metabolites might be a component of the cascade of reactions initiated by luteinizing hormone-releasing hormone that ultimately results in secretion of luteinizing hormone. PMID:6344087

  9. Electrochemical biosensors for hormone analyses.

    PubMed

    Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

    2015-06-15

    Electrochemical biosensors have a unique place in determination of hormones due to simplicity, sensitivity, portability and ease of operation. Unlike chromatographic techniques, electrochemical techniques used do not require pre-treatment. Electrochemical biosensors are based on amperometric, potentiometric, impedimetric, and conductometric principle. Amperometric technique is a commonly used one. Although electrochemical biosensors offer a great selectivity and sensitivity for early clinical analysis, the poor reproducible results, difficult regeneration steps remain primary challenges to the commercialization of these biosensors. This review summarizes electrochemical (amperometric, potentiometric, impedimetric and conductometric) biosensors for hormone detection for the first time in the literature. After a brief description of the hormones, the immobilization steps and analytical performance of these biosensors are summarized. Linear ranges, LODs, reproducibilities, regenerations of developed biosensors are compared. Future outlooks in this area are also discussed.

  10. Hormones and prostate cancer: what's next?

    PubMed

    Hsing, A W

    2001-01-01

    In summary, the hormonal hypothesis remains one of the most important hypotheses in prostate cancer etiology. Although epidemiologic data regarding the role of hormones are still inconclusive, there are many intriguing leads. Armed with more complete methodological data, state-of-the-art hormone assays, sound epidemiologic design, and a more thorough analytical approach, a new generation of studies should yield critical data and insights to help clarify further the role of hormones in prostate cancer. These new studies may determine ultimately whether racial/ethnic differences in hormonal levels and in genetic susceptibility to hormone-metabolizing genes can help explain the very large racial/ethnic differences in prostate cancer risk.

  11. [Premenstrual asthma: relation to hormones].

    PubMed

    Hernández Colin, D; Zárate Treviño, A; Martínez Cairo Cueto, S

    1997-01-01

    Exacerbation of asthmatic symptoms just before or at the time of menstruation documented in some women with asthma has been called "premenstrual asthma" (PMA). The effect of sex hormones on airway function has not been well studied in spite of much evidence to suggest, therefore about relationships between the sex hormones and airway. The investigations of (PMA) have been based on studies of asthmatics already aware of a deterioration of asthma premenstrually. Little is known, therefore, about relationships between the menstrual cycle with asthma and (PMA) subjects. Although the mechanism of PMA remains unclear.

  12. Principles and pitfalls of free hormone measurements.

    PubMed

    Faix, James D

    2013-10-01

    The free hormone hypothesis states that a hormone's physiological effects depend on the free hormone concentration, not the total hormone concentration. Although the in vivo relationship between free hormone and protein-bound hormone is complex, most experts have applied this view to the design of assays used to assess the free hormone concentration in the blood sampled for testing in vitro. The history of the measurement of free thyroxine, probably the most frequently requested free hormone determination, offers a good example of the approaches that have been taken. Methods that require physical separation of the free hormone from the protein-bound hormone must address both the potential disturbance in the equilibrium between the two, as well as the challenge of quantifying small levels of hormone accurately and precisely. The implementation of mass spectrometry in the clinical laboratory has helped to develop proposed reference measurement procedures. These must be utilized to standardize the variety of immunoassay approaches that currently represent options commercially available to the routine clinical laboratory. Practicing endocrinologists should discuss the details of the free hormone assays offered by the clinical laboratory they utilize for patient result reporting, and clinical laboratories should implement the recommendations of published guidelines to ensure that free hormone results using commercially available immunoassays are as accurate and precise as possible.

  13. 'Love Hormone' Helps Dads and Babies Bond

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163657.html 'Love Hormone' Helps Dads and Babies Bond Brain scans ... 2017 FRIDAY, Feb. 17, 2017 (HealthDay News) -- The "love hormone" oxytocin may program fathers to bond with ...

  14. Parathyroid hormone-related protein blood test

    MedlinePlus

    ... gov/ency/article/003691.htm Parathyroid hormone-related protein blood test To use the sharing features on ... page, please enable JavaScript. The parathyroid hormone-related protein (PTH-RP) test measures the level of a ...

  15. The concept of multiple hormonal dysregulation.

    PubMed

    Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Ferrucci, Luigi; Luci, Michele; Valenti, Giorgio; Ceda, Gianpaolo

    2010-01-01

    Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones that remain stable and anabolic hormones (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Despite the multiple hormonal dysregulation occurring with age, the prevalent line of research in the last decades has tried to explain many age-related phenomena as consequence of one single hormonal derangement with disappointing results. In this review we will list the relationship between hormonal anabolic deficiency and frailty and mortality in older population, providing evidence to the notion that multiple hormonal dysregulation rather than change in single anabolic hormone is a powerful marker of poor health status and mortality.

  16. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  17. Thyroid Hormones as Renal Cell Cancer Regulators

    PubMed Central

    Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

    It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma. PMID:27034829

  18. "Sex Hormones" in Secondary School Biology Textbooks

    ERIC Educational Resources Information Center

    Nehm, Ross H.; Young, Rebecca

    2008-01-01

    This study explores the extent to which the term "sex hormone" is used in science textbooks, and whether the use of the term "sex hormone" is associated with pre-empirical concepts of sex dualism, in particular the misconceptions that these so-called "sex hormones" are sex specific and restricted to sex-related physiological functioning. We found…

  19. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production

    PubMed Central

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    2016-01-01

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET. PMID:27746436

  20. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production.

    PubMed

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET.

  1. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    SciTech Connect

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. )

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin (cis-diamminedichloroplatinum(II)) and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  2. Parathyroid hormone - Secretion and metabolism in vivo.

    NASA Technical Reports Server (NTRS)

    Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

    1971-01-01

    Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

  3. Hormonal treatment of acne vulgaris: an update

    PubMed Central

    Elsaie, Mohamed L

    2016-01-01

    Acne vulgaris is a common skin condition associated with multiple factors. Although mostly presenting alone, it can likewise present with features of hyperandrogenism and hormonal discrepancies. Of note, hormonal therapies are indicated in severe, resistant-to-treatment cases and in those with monthly flare-ups and when standard therapeutic options are inappropriate. This article serves as an update to hormonal pathogenesis of acne, discusses the basics of endocrinal evaluation for patients with suspected hormonal acne, and provides an overview of the current hormonal treatment options in women. PMID:27621661

  4. Thyroid hormone and dehydroepiandrosterone permit gluconeogenic hormone responses in hepatocytes.

    PubMed

    Kneer, N; Lardy, H

    2000-03-01

    The importance of the sn-glycerol- 3-phosphate (G-3-P) electron transfer shuttle in hormonal regulation of gluconeogenesis was examined in hepatocytes from rats with decreased mitochondrial G-3-P dehydrogenase activity (thyroidectomized) or increased G-3-P dehydrogenase activity [triiodothyronine (T(3)) or dehydroepiandrosterone (DHEA) treated]. Rates of glucose formation from 10 mM lactate, 10 mM pyruvate, or 2.5 mM dihydroxyacetone were somewhat less in hypothyroid cells than in cells from normal rats but gluconeogenic responses to calcium addition and to norepinephrine (NE), glucagon (G), or vasopressin (VP) were similar to the responses observed in cells from normal rats. However, with 2. 5 mM glycerol or 2.5 mM sorbitol, substrates that must be oxidized in the cytosol before conversion to glucose, basal gluconeogenesis was not appreciably altered by hypothyroidism but responses to calcium and to the calcium-mobilizing hormones were abolished. Injecting thyroidectomized rats with T(3) 2 days before preparing the hepatocytes greatly enhanced gluconeogenesis from glyc erol and restored the response to Ca(2+) and gluconeogenic hormones. Feeding dehydroepiandrosterone for 6 days depressed gluconeogenesis from lactate or pyruvate but substantially increased glucose production from glycerol in euthyroid cells and restored responses to Ca(2+) in hypothyroid cells metabolizing glycerol. Euthyroid cells metabolizing glycerol or sorbitol use the G-3-P and malate/aspartate shuttles to oxidize excess NADH generated in the cytosol. The transaminase inhibitor aminooxyacetate (AOA) decreased gluconeogenesis from glycerol 40%, but had little effect on responses to Ca(2+) and NE. However, in hypothyroid cells, with minimal G-3-P dehydrogenase, AOA decreased gluconeogenesis from glycerol more than 90%. Thus, the basal rate of gluconeogenesis from glycerol in the euthyroid cells is only partly dependent on electron transport from cytosol to mitochondria via the malate

  5. [Hormones and hair growth in man].

    PubMed

    Moretti, G; Rampini, E; Rebora, A

    1977-12-01

    A literature review tries to diminish the ambiguity between hormones and hairs. Therefore the hormonal action in general (regulation of the protein synthesis indirectly by enzymatical regulation of the AMP-system or directly by hormones as active metabolites) and the methods to explore hormones-hair-interaction are discussed. Hormones pertaining to the pituitary-adrenal-gonadal axis are regarded as the paramount hormones; therefore the results of research in testosterone, 5-alpha-dihydrotestosterone, estrogens, progesterone, glucocorticoids, the hypophysis and its tropins are recapitulated. The main disorders of hair-growth, pattern baldness and "idiopathic" hirsutism, which would be dependent on a similar disturbance of androgen metabolism, are discussed. Pathology in hair-growth may arise in any point of the cascade of hormone action.

  6. Hormone interactions during lateral root formation.

    PubMed

    Fukaki, Hidehiro; Tasaka, Masao

    2009-03-01

    Lateral root (LR) formation, the production of new roots from parent roots, is a hormone- and environmentally-regulated developmental process in higher plants. Physiological and genetic studies using Arabidopsis thaliana and other plant species have revealed the roles of several plant hormones in LR formation, particularly the role of auxin in LR initiation and primordium development, resulting in much progress toward understanding the mechanisms of auxin-mediated LR formation. However, hormone interactions during LR formation have been relatively underexamined. Recent studies have shown that the plant hormones, cytokinin and abscisic acid negatively regulate LR formation whereas brassinosteroids positively regulate LR formation. On the other hand, ethylene has positive and negative roles during LR formation. This review summarizes recent findings on hormone-regulated LR formation in higher plants, focusing on auxin as a trigger and on the other hormones in LR formation, and discusses the possible interactions among plant hormones in this developmental process.

  7. Progestogens in menopausal hormone therapy

    PubMed Central

    Woroń, Jarosław

    2015-01-01

    Progestogens share one common effect: the ability to convert proliferative endometrium to its secretory form. In contrast, their biological activity is varied, depending on the chemical structure, pharmacokinetics, receptor affinity and different potency of action. Progestogens are widely used in the treatment of menstrual cycle disturbances, various gynaecological conditions, contraception and menopausal hormone therapy. The administration of progestogen in menopausal hormone therapy is essential in women with an intact uterus to protect against endometrial hyperplasia and cancer. Progestogen selection should be based on the characteristics available for each progestogen type, relying on the assessment of relative potency of action in experimental models and animal models, and on the indirect knowledge brought by studies of the clinical use of different progestogen formulations. The choice of progestogen should involve the conscious use of knowledge of its benefits, with a focus on minimizing potential side effects. Unfortunately, there are no direct clinical studies comparing the metabolic effects of different progestogens. PMID:26327902

  8. Obesity and hormonal contraceptive efficacy.

    PubMed

    Robinson, Jennifer A; Burke, Anne E

    2013-09-01

    Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

  9. Modelling hormonal response and development.

    PubMed

    Voß, Ute; Bishopp, Anthony; Farcot, Etienne; Bennett, Malcolm J

    2014-05-01

    As our knowledge of the complexity of hormone homeostasis, transport, perception, and response increases, and their outputs become less intuitive, modelling is set to become more important. Initial modelling efforts have focused on hormone transport and response pathways. However, we now need to move beyond the network scales and use multicellular and multiscale modelling approaches to predict emergent properties at different scales. Here we review some examples where such approaches have been successful, for example, auxin-cytokinin crosstalk regulating root vascular development or a study of lateral root emergence where an iterative cycle of modelling and experiments lead to the identification of an overlooked role for PIN3. Finally, we discuss some of the remaining biological and technical challenges.

  10. Ovarian hormones and drug abuse.

    PubMed

    Moran-Santa Maria, Megan M; Flanagan, Julianne; Brady, Kathleen

    2014-11-01

    There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women's health. In this review we will discuss findings from clinical and preclinical studies of (1) reproductive cycle phase; (2) endogenous ovarian hormones; and (3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.

  11. A Simulated Growth Hormone Analysis

    NASA Astrophysics Data System (ADS)

    Harris, Mary

    1996-08-01

    Growth hormone is a drug that is sometimes abused by amateur or professional athletes for performance-enhancement. This laboratory is a semimicroscale simulation analysis of a sample of "urine" to detect proteins of two very different molecular weights. Gel filtration uses a 10 mL disposable pipette packed with Sephadex. Students analyze the fractions from the filtration by comparing colors of the Brilliant Blue Coomassie Dye as it interacts with the proteins in the sample to a standard set of known concentration of protein with the dye. The simulated analysis of growth hormone is intended to be included in a unit on organic chemistry or in the second year of high school chemistry.

  12. Hormone therapy and cognitive function

    PubMed Central

    Maki, Pauline M.; Sundermann, Erin

    2009-01-01

    BACKGROUND Clinical trials yield discrepant information about the impact of hormone therapy on verbal memory and executive function. This issue is clinically relevant because declines in verbal memory are the earliest predictor of Alzheimer's disease and declines in executive function are central to some theories of normal, age-related changes in cognition. METHODS We conducted a systematic review of randomized clinical trials of hormone therapy (i.e. oral, transdermal, i.m.) and verbal memory, distinguishing studies in younger (i.e. ≤65 years of age; n = 9) versus older (i.e. >65 years; n = 7) women and studies involving estrogen alone versus estrogen plus progestogen. Out of 32 placebo-controlled trials, 17 were included (13 had no verbal memory measures and 2 involved cholinergic manipulations). We also provide a narrative review of 25 studies of executive function (two trials), since there are insufficient clinical trial data for systematic review. RESULTS There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women. There is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women. Observational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy. CONCLUSIONS Future studies should include measures of executive function and should address pressing clinical questions; including what formulation of combination hormone therapy is cognitively neutral/beneficial, yet effective in treating hot flashes in the early post-menopause. PMID:19468050

  13. Ghrelin and obestatin modulate growth hormone-releasing hormone release and synaptic inputs onto growth hormone-releasing hormone neurons.

    PubMed

    Feng, Dan D; Yang, Seung-Kwon; Loudes, Catherine; Simon, Axelle; Al-Sarraf, Tamara; Culler, Michael; Alvear-Perez, Rodrigo; Llorens-Cortes, Catherine; Chen, Chen; Epelbaum, Jacques; Gardette, Robert

    2011-09-01

    Ghrelin, a natural ligand of the growth hormone secretagogue receptor (GHS-R), is synthesized in the stomach but may also be expressed in lesser quantity in the hypothalamus where the GHS-R is located on growth hormone-releasing hormone (GHRH) neurons. Obestatin, a peptide derived from the same precursor as ghrelin, is able to antagonize the ghrelin-induced increase of growth hormone (GH) secretion in vivo but not from pituitary explants in vitro. Thus, the blockade of ghrelin-induced GH release by obestatin could be mediated at the hypothalamic level by the neuronal network that controls pituitary GH secretion. Ghrelin increased GHRH and decreased somatostatin (somatotropin-releasing inhibitory factor) release from hypothalamic explants, whereas obestatin only reduced the ghrelin-induced increase of GHRH release, thus indicating that the effect of ghrelin and obestatin is targeted to GHRH neurons. Patch-clamp recordings on mouse GHRH-enhanced green fluorescent protein neurons indicated that ghrelin and obestatin had no significant effects on glutamatergic synaptic transmission. Ghrelin decreased GABAergic synaptic transmission in 44% of the recorded neurons, an effect blocked in the presence of the GHS-R antagonist BIM28163, and stimulated the firing rate of 78% of GHRH neurons. Obestatin blocked the effects of ghrelin by acting on a receptor different from the GHS-R. These data suggest that: (i) ghrelin increases GHRH neuron excitability by increasing their action potential firing rate and decreasing the strength of GABA inhibitory inputs, thereby leading to an enhanced GHRH release; and (ii) obestatin counteracts ghrelin actions. Such interactions on GHRH neurons probably participate in the control of GH secretion.

  14. Thyroid Hormone Regulation of Metabolism

    PubMed Central

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

  15. Parathyroid Hormone Levels and Cognition

    NASA Technical Reports Server (NTRS)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  16. Are female sex hormones teratogenic?

    PubMed

    Wilson, J G; Brent, R L

    1981-11-01

    An analysis of available epidemiologic data leads the present reviewers to conclude that the use of exogenous hormones during human pregnancy has not been proved to cause developmental abnormality in nongenital organs and tissues. This conclusion is further supported by the animal laboratory data. The preponderance of evidence at this writing indicates a lack of causal association between hormonal use during pregnancy and nongenital malformation of the offspring. The quality of the epidemiologic data does not, at this time, permit a definitive conclusion that sex hormones during pregnancy may not, under as yet to be defined conditions, have some adverse effect on human prenatal development. If there are increased risks of nongenital malformations associated with the administration of certain sex steroids, the risks are very small, may not be causal, and are substantially below the spontaneous risk of malformations. In spite of the present degree of uncertainty, the clinical, epidemiologic, and laboratory data do permit the formulation of a rational approach to handling problems related to sex steroid usage and exposure in pregnant women.

  17. Sex Hormones and Macronutrient Metabolism

    PubMed Central

    Comitato, Raffaella; Saba, Anna; Turrini, Aida; Arganini, Claudia; Virgili, Fabio

    2015-01-01

    The biological differences between males and females are determined by a different set of genes and by a different reactivity to environmental stimuli, including the diet, in general. These differences are further emphasized and driven by the exposure to a different hormone flux throughout the life. These differences have not been taken into appropriate consideration by the scientific community. Nutritional sciences are not immune from this “bias” and when nutritional needs are concerned, females are considered only when pregnant, lactating or when their hormonal profile is returning back to “normal,” i.e., to the male-like profile. The authors highlight some of the most evident differences in aspects of biology that are associated with nutrition. This review presents and describes available data addressing differences and similarities of the “reference man” vs. the “reference woman” in term of metabolic activity and nutritional needs. According to this assumption, available evidences of sex-associated differences of specific biochemical pathways involved in substrate metabolism are reported and discussed. The modulation by sexual hormones affecting glucose, amino acid and protein metabolism and the metabolization of nutritional fats and the distribution of fat depots, is considered targeting a tentative starting up background for a gender concerned nutritional science. PMID:24915409

  18. Hormonal and lactational responses to growth hormone-releasing hormone treatment in lactating Japanese Black cows.

    PubMed

    Shingu, H; Hodate, K; Kushibiki, S; Ueda, Y; Touno, E; Shinoda, M; Ohashi, S

    2004-06-01

    Ten multiparous lactating Japanese Black cows (beef breed) were used to evaluate the effects of bovine growth hormone-releasing hormone (GHRH) analog on milk yield and profiles of plasma hormones and metabolites. The cows received 2 consecutive 21-d treatments (a daily s.c. injection of 3-mg GHRH analog or saline) in a 2 (group) x 2 (period) Latin square crossover design. The 5 cows in group A received GHRH analog during period 1 (from d 22 to 42 postpartum) and saline during period 2 (from d 57 to 77 postpartum), and those in group B received saline and GHRH analog during periods 1 and 2, respectively. Mean milk yield decreased in saline treated compared with that during the 1-wk period before treatment 7.4 and 19.1% during periods 1 (group B) and 2 (group A), respectively. Treatment with GHRH analog increased milk yield 17.4% (period 1, group A) and 6.3% (period 2, group B). Treatment with GHRH analog induced higher basal plasma concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin, and glucose compared with saline-treated cows. In glucose challenge, the GHRH analog-treated beef cows had greater insulin secretion than the saline-treated beef cows. In insulin challenge, however, there were no significant differences in the areas surrounded by hypothetical lines of basal glucose concentrations and glucose response curves between GHRH analog- and saline-treated cows. These results demonstrate that GHRH analog treatment facilitates endogenous GH secretion in lactating Japanese Black cows, leading to increases in milk yield and plasma concentrations of IGF-1, insulin, and glucose.

  19. Hormone symphony during root growth and development.

    PubMed

    Garay-Arroyo, Adriana; De La Paz Sánchez, María; García-Ponce, Berenice; Azpeitia, Eugenio; Alvarez-Buylla, Elena R

    2012-12-01

    Hormones regulate plant growth and development in response to external environmental stimuli via complex signal transduction pathways, which in turn form complex networks of interaction. Several classes of hormones have been reported, and their activity depends on their biosynthesis, transport, conjugation, accumulation in the vacuole, and degradation. However, the activity of a given hormone is also dependent on its interaction with other hormones. Indeed, there is a complex crosstalk between hormones that regulates their biosynthesis, transport, and/or signaling functionality, although some hormones have overlapping or opposite functions. The plant root is a particularly useful system in which to study the complex role of plant hormones in the plastic control of plant development. Physiological, cellular, and molecular genetic approaches have been used to study the role of plant hormones in root meristem homeostasis. In this review, we discuss recent findings on the synthesis, signaling, transport of hormones and role during root development and examine the role of hormone crosstalk in maintaining homeostasis in the apical root meristem.

  20. Gastrointestinal hormone research - with a Scandinavian annotation.

    PubMed

    Rehfeld, Jens F

    2015-06-01

    Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization or differentiated posttranslational maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed outside the gut, some only in extraintestinal endocrine cells and cerebral or peripheral neurons but others also in other cell types. The extraintestinal cells may release different bioactive fragments of the same prohormone due to cell-specific processing pathways. Moreover, endocrine cells, neurons, cancer cells and, for instance, spermatozoa secrete gut peptides in different ways, so the same peptide may act as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions, but also constitute regulatory systems operating in the whole organism. This overview of gut hormone biology is supplemented with an annotation on some Scandinavian contributions to gastrointestinal hormone research.

  1. Identification and localization of gastrointestinal hormones in the skin of the bullfrog Rana catesbeiana during periods of activity and hibernation.

    PubMed

    Wang, Huan; Zhou, Naizhen; Zhang, Rui; Wu, Yuanyuan; Zhang, Ruidong; Zhang, Shengzhou

    2014-10-01

    Amphibian skin and its secretions contain a wide variety of biogenic amines and biologically active peptides, some of which are either identical or highly homologous to gastrointestinal hormones (GHs) of higher vertebrates. This study investigated the distribution density and immunoreactive (IR) intensity of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS), pancreatic polypeptide (PP), neuropeptide Y (NPY) and glucagon (GLU) IR cells in the skin of the bullfrog Rana catesbeiana during periods of activity and hibernation. The results indicated that the six types of GHs were all present in the bullfrog skin and were most predominant in the epidermis and mucous glands. In dorsal skin, the density of the GHs-IR cells in mucous glands was higher than that in epidermis except for GAS-IR cells. In ventral skin, the density of 5-HT, PP and NPY-IR cells in mucous glands was also higher than that in the epidermis. During hibernation, the density of the six types of GHs-IR cells and the IR intensity of GAS, SS, NPY and GLU-IR cells in the epidermis of dorsal skin increased significantly. The IR intensity of SS, PP and NPY-IR cells in granular glands of ventral skin also increased significantly during hibernation. These results suggested that multiple types of GHs-IR cells present in the skin of R. catesbeiana, may play important roles in the regulation of the physiological functions of skin. Also, adaptive changes in the density and IR intensity of GHs-IR cells occurred during hibernation.

  2. Soluble dietary fiber (Fibersol-2) decreased hunger and increased satiety hormones in humans when ingested with a meal.

    PubMed

    Ye, Zhong; Arumugam, Visalakshi; Haugabrooks, Esther; Williamson, Patricia; Hendrich, Suzanne

    2015-05-01

    We hypothesized that a digestion-resistant maltodextrin, Fibersol-2 (Archer Daniels Midland/Matsutani LLC, Decatur, IL, USA) may impact satiety by decreasing hunger, prolonging satiation, and/or increasing peripheral satiety signals. In a randomized, double-blind, placebo-controlled crossover study, healthy subjects (9 men and 10 women) underwent 3 treatments in which they consumed a standardized meal with a tea containing 0, 5, or 10 g of Fibersol-2. A visual analog scale questionnaire was given in 30-minute intervals to measure subjective appetite and satiety. Blood was drawn just before the meal (time 0) and at 30, 60, 90, 120, 180, and 240 minutes after meal for measurements of plasma ghrelin, cholecystokinin, gastrin, peptide YY, gastric inhibitory polypeptide, and glucagon-like peptide-1, all by enzyme-linked immunosorbent assay. There were significant delays in hunger and increased satiety for 1.5 to 2 hours after treatment with 10 g of Fibersol-2. These delays did not occur after ingesting 0 or 5 g Fibersol-2 at any time. Control and 5 g Fibersol-2 treatments did not suppress increases in hunger postmeal; hunger scores increased and satiety scores decreased significantly (P < .05) at all time points relative to the first postmeal assessment. Plasma peptide YY and glucagon-like peptide-1 were significantly increased by the ingestion of meal with tea containing 10 g Fibersol-2 compared with 0 or 5 g Fibersol-2 (P < .05). This study demonstrated that 10 g Fibersol-2 with a meal stimulated production of satiety hormones and enhanced satiety.

  3. Expression of growth hormone and growth hormone receptor in fibroadenomas of the breast.

    PubMed

    Lenicek, Tanja; Kasumović, Dino; Stajduhar, Emil; Dzombeta, Tihana; Jukić, Zoran; Kruslin, Bozo

    2013-06-01

    Fibroadenoma is the most prevalent benign breast tumor. It consists of epithelial and stromal components. In general, breast tumors are highly hormonally dependent and growth hormone by its physiology may have a possible oncogenic potential. Therefore, the aim of this study was to determine the expression of growth hormone and growth hormone receptor in epithelial and stromal components of fibroadenomas. Study group included 30 randomly chosen fibroadenomas from female patients aged between 18 and 69 years. The expression of growth hormone and growth hormone receptor was defined in both histologic components of fibroadenomas. Growth hormone was expressed in 96.7% of both epithelial and stromal components of fibroadenomas, with stronger expression in the stromal component. The same percentage of positive reaction (96.7%) was obtained in the epithelial component of fibroadenomas for growth hormone receptor expression. Only 6.7% of stromal components tested for growth hormone receptor were positive. The high expression of growth hormone and growth hormone receptor in fibroadenoma tissue indicates their possible role in the pathogenesis of this tumor. Follow up of patients with high expression of growth hormone and growth hormone receptor may be suggested.

  4. Do hormones influence melanoma? Facts and controversies.

    PubMed

    Gupta, Amie; Driscoll, Marcia S

    2010-01-01

    The issue of whether hormones influence malignant melanoma (MM) has been controversial for many years. Although early case reports demonstrated a negative effect of hormones, recent evidence has not supported a potential role for hormones in MM. We address whether exogenous and endogenous hormones influence a woman's risk for MM or affect her prognosis if diagnosed with MM. Multiple epidemiologic studies show the use of oral contraceptives or hormone replacement therapy does not appear to increase a woman's risk for MM. Pregnancy does not appear to influence a woman's risk of MM, nor does pregnancy appear to affect prognosis in the woman diagnosed with MM. When counseling the woman who is diagnosed with MM during pregnancy or during the childbearing years, future use of oral contraceptives or hormone replacement therapy is not contraindicated; counseling concerning future pregnancies should be done on a case-by-case basis, with emphasis placed on established prognostic factors for MM.

  5. Hormones and sexual orientation: a questionable link.

    PubMed

    Banks, A; Gartrell, N K

    1995-01-01

    This paper critically reviews the studies which explore a possible causal relationship between sex hormones and the development of sexual orientation. Early studies focused on hormone measurements in adult men and women. While definitive interpretations are hindered by methodological problems, the studies as a whole do not support a causal relationship between postnatal hormone levels and sexual orientation. More recently, a theory that prenatal hormone levels produce varying degrees of brain androgenization and subsequent dimorphic sex role behavior has consistently been supported by studies in lower mammals. Attempts to generalize the causes of sexual orientation from animals to humans have been controversial. Efforts to measure the estrogen feedback as an indication of brain androgenization have produced inconsistent results. Studies of men and women who experienced defect in hormone metabolism (i.e., CAH and testicular feminization) have not found a concurrent increase in homosexual behavior. Overall, the data do not support a causal connection between hormones and human sexual orientation.

  6. Thyroid hormone resistance and its management

    PubMed Central

    Lado-Abeal, Joaquin

    2016-01-01

    The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Patients can present with symptoms of hyperthyroidism or hypothyroidism. They usually have elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone level. Due to their nonspecific symptomatic presentation, these patients can be misdiagnosed if the primary care physician is not familiar with the condition. This can result in frustration for the patient and sometimes unnecessary invasive treatment such as radioactive iodine ablation, as in the case presented herein. PMID:27034574

  7. Sex steroids and growth hormone interactions.

    PubMed

    Fernández-Pérez, Leandro; de Mirecki-Garrido, Mercedes; Guerra, Borja; Díaz, Mario; Díaz-Chico, Juan Carlos

    2016-04-01

    GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of sex hormones on the liver may be direct, through hepatic receptors, or indirect by modulating endocrine, metabolic, and gender-differentiated functions of GH. Sex hormones can modulate GH actions by acting centrally, regulating pituitary GH secretion, and peripherally, by modulating GH signaling pathways. The endocrine and/or metabolic consequences of long-term exposure to sex hormone-related compounds and their influence on the GH-liver axis are largely unknown. A better understanding of these interactions in physiological and pathological states will contribute to preserve health and to improve clinical management of patients with growth, developmental, and metabolic disorders.

  8. Endocrine disruptors and thyroid hormone physiology.

    PubMed

    Jugan, Mary-Line; Levi, Yves; Blondeau, Jean-Paul

    2010-04-01

    Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame-retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

  9. Hormonal regulation of fetal growth.

    PubMed

    Gicquel, C; Le Bouc, Y

    2006-01-01

    Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients and oxygen to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. Hormones play a central role in regulating fetal growth and development. They act as maturational and nutritional signals in utero and control tissue development and differentiation according to the prevailing environmental conditions in the fetus. The insulin-like growth factor (IGF) system, and IGF-I and IGF-II in particular, plays a critical role in fetal and placental growth throughout gestation. Disruption of the IGF1, IGF2 or IGF1R gene retards fetal growth, whereas disruption of IGF2R or overexpression of IGF2 enhances fetal growth. IGF-I stimulates fetal growth when nutrients are available, thereby ensuring that fetal growth is appropriate for the nutrient supply. The production of IGF-I is particularly sensitive to undernutrition. IGF-II plays a key role in placental growth and nutrient transfer. Several key hormone genes involved in embryonic and fetal growth are imprinted. Disruption of this imprinting causes disorders involving growth defects, such as Beckwith-Wiedemann syndrome, which is associated with fetal overgrowth, or Silver-Russell syndrome, which is associated with intrauterine growth retardation. Optimal fetal growth is essential for perinatal survival and has long-term consequences extending into adulthood. Given the high incidence of intrauterine growth retardation and the high risk of metabolic and cardiovascular complications in later life, further clinical and basic research is needed to develop accurate early diagnosis of aberrant fetal growth and novel therapeutic strategies.

  10. Aluminum, parathyroid hormone, and osteomalacia

    SciTech Connect

    Burnatowska-Hledin, M.A.; Kaiser, L.; Mayor, G.H.

    1983-01-01

    Aluminum exposure in man is unavoidable. The occurrence of dialysis dementia, vitamin D-resistant osteomalacia, and hypochromic microcytic anemia in dialysis patients underscores the potential for aluminum toxicity. Although exposure via dialysate and hyperalimentation leads to significant tissue aluminum accumulation, the ubiquitous occurrence of aluminum and the severe pathology associated with large aluminum burdens suggest that smaller exposures via the gastrointestinal tract and lungs could represent an important, though largely unrecognized, public health problem. It is clear that some aluminum absorption occurs with the ingestion of small amounts of aluminum in the diet and medicines, and even greater aluminum absorption is seen in individuals consuming large amounts of aluminum present in antacids. Aluminum absorption is enhanced in the presence of elevated circulating parathyroid hormone. In addition, elevated PTH leads to the preferential deposition of aluminum in brain and bone. Consequently, PTH is likely to be involved in the pathogenesis of toxicities in those organs. PTH excess also seems to lead to the deposition of aluminum in the parathyroid gland. The in vitro demonstration that aluminum inhibits parathyroid hormone release is consistent with the findings of a euparathyroid state in dialysis patients with aluminum related vitamin D-resistant osteomalacia. Nevertheless, it seems likely that hyperparathyroidism is at least initially involved in the pathogenesis of aluminum neurotoxicity and osteomalacia; the increases in tissue aluminum stores are followed by suppression of parathyroid hormone release, which is required for the evolution of osteomalacia. Impaired renal function is not a prerequisite for increased tissue aluminum burdens, nor for aluminum-related organ toxicity. Consequently, it is likely that these diseases will be observed in populations other than those with chronic renal disease.

  11. Review of hormonal treatment of breast cancer.

    PubMed

    Abdulkareem, I H; Zurmi, I B

    2012-01-01

    This critical review focuses on the role of steroid hormones and their receptors in the development and treatment of breast cancer, with special reference to estrogen receptors, as well as mechanisms of receptor-ligand interactions, response or resistance to hormonal therapy against breast cancer, in conjunction with other modalities like surgery and chemotherapy. Tamoxifen is used in hormonal treatment of breast cancer for up to five years, depending on the presentation. However, there have been recent developments in hormonal therapy of breast cancer in the last ten years, with the introduction of many different alternative therapies for this condition. A critical review of published articles in Pubmed/Medline, Athens, AJOL, NHS Evidence, Science Direct and Google, relating to hormonal treatment of breast cancer, was undertaken, in order to evaluate the mechanisms of estrogen receptor-ligand interactions, their involvement in the etio-pathogenesis of breast cancer, resistance of breast cancer cells to anti-hormonal agents, as well as ways of treating breast cancer using anti-hormone drugs like tamoxifen. Although tamoxifen is the established drug for hormonal treatment of breast cancer, cases of hormone resistance breast cancer have been described recently in the literature. This can happen from the beginning, or during treatment. Therefore, we aim to examine the causes of resistance to hormonal treatment with a view to understand the options of tackling this problem, and suggest other novel alternative hormonal therapies that can be tried, which may overtake tamoxifen in the future. We also seek to emphasize that hormonal therapy has a definite place in the treatment of breast cancer along with surgery, chemotherapy and radiotherapy, as the disease is often considered to be multi-systemic even from the beginning.

  12. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2005-08-01

    neurofibroma and MPNST Schwann cells. We found less than 2-fold difference in these transcripts in tumor versus normal Schwann cells (in those that changed...neurofibromin-negative) to steroid hormones, focusing on estrogen and progesterone. The hypothesis is that human neurofibroma (and MPNST , malignant...to determine steroid hormone receptor expression in human normal, NF1 neurofibroma, and NF1 MPNST Schwann cells, pre- and post-hormone treatment by

  13. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2002-08-01

    hypothesis is that human neurofibroma (and/or MPNST ) Schwann cells have increased hormone response compared to normal Schwann cells, leading to tumor...growth. Specific Aim 1 will determine steroid hormone receptor expression in human normal, NFl neurofibroma and MPNST Schwann cells. Real-time PCR has...and rat Schwann cells, as well as an MPNST line so far (which showed no proliferative response) Specific Aim 3 involves in vivo hormone response of

  14. Hormonal therapy of prostate cancer.

    PubMed

    Labrie, Fernand

    2010-01-01

    Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood. Consequently, after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin. In fact, while elimination of testicular androgens by castration alone has never been shown to prolong life in metastatic prostate cancer, combination of castration (surgical or medical with a gonadotropin-releasing hormone (GnRH) agonist) with a pure anti-androgen has been the first treatment shown to prolong life. Most importantly, when applied at the localized stage, the same combined androgen blockade (CAB) can provide long-term control or cure of the disease in more than 90% of cases. Obviously, since prostate cancer usually grows and metastasizes without signs or symptoms, screening with prostate-specific antigen (PSA) is absolutely needed to diagnose prostate cancer at an 'early' stage before metastasis occurs and the cancer becomes non-curable. While the role of androgens was believed to have become non-significant in cancer progressing under any form of androgen blockade, recent data have shown increased expression of the androgen receptor (AR) in treatment-resistant disease with a benefit of further androgen blockade. Since the available anti-androgens have low affinity for AR and cannot block androgen action completely

  15. [Hormonal therapy in breast cancer].

    PubMed

    Espinós, J; Reyna, C; de la Cruz, S; Oiler, C; Hernández, A; Fernández Hidalgo, O; Santisteban, M; García Foncillas, J

    2008-01-01

    Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.

  16. Sexual hormone fluctuation in chinchillas.

    PubMed

    Celiberti, Simone; Gloria, Alessia; Contri, Alberto; Carluccio, Augusto; Peric, Tanja; Melillo, Alessandro; Robbe, Domenico

    2013-01-01

    The data about chinchilla (Chinchilla laniger) reproduction are limited and in some cases discordant. The aim of this study was to monitor the sexual hormone fluctuation by fecal progesterone level and colpocytology analysis by vaginal smears in order to evaluate the different phases of the oestrus cycle. Twenty-four non pregnant chinchillas aged from 1 to 4 years old and subdivided in three groups were monitored. In contrast with findings reported in other study, the high values of progesterone recorded in autumn suggested the presence of a ciclicity also in this period. The data indicate that chinchilla presents a continuous cycle.

  17. Hormone cross-talk during seed germination.

    PubMed

    Gazzarrini, Sonia; Tsai, Allen Yi-Lun

    2015-01-01

    Hormones are chemical substances that can affect many cellular and developmental processes at low concentrations. Plant hormones co-ordinate growth and development at almost all stages of the plant's life cycle by integrating endogenous signals and environmental cues. Much debate in hormone biology revolves around specificity and redundancy of hormone signalling. Genetic and molecular studies have shown that these small molecules can affect a given process through a signalling pathway that is specific for each hormone. However, classical physiological and genetic studies have also demonstrated that the same biological process can be regulated by many hormones through independent pathways (co-regulation) or shared pathways (cross-talk or cross-regulation). Interactions between hormone pathways are spatiotemporally controlled and thus can vary depending on the stage of development or the organ being considered. In this chapter we discuss interactions between abscisic acid, gibberellic acid and ethylene in the regulation of seed germination as an example of hormone cross-talk. We also consider hormone interactions in response to environmental signals, in particular light and temperature. We focus our discussion on the model plant Arabidopsis thaliana.

  18. Growth Hormone and Craniofacial Tissues. An update

    PubMed Central

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

  19. Hormones and the blood-brain barrier.

    PubMed

    Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

    2015-03-01

    Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

  20. Effects of hormones on platelet aggregation.

    PubMed

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J

    2014-04-01

    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  1. Thyroid hormone transporters in the brain.

    PubMed

    Suzuki, Takehiro; Abe, Takaaki

    2008-01-01

    Thyroid hormone plays an essential role in proper mammalian development of the central nervous system and peripheral tissues. Lack of sufficient thyroid hormone results in abnormal development of virtually all organ systems, a syndrome termed cretinism. In particular, hypothyroidism in the neonatal period causes serious damage to neural cells and leads to mental retardation. Although thyroxine is the major product secreted by the thyroid follicular cells, the action of thyroid hormone is mediated mainly through the deiodination of T(4) to the biologically active form 3,3', 5-triiodo-L-thyronine, followed by the binding of T(3) to a specific nuclear receptor. Before reaching the intracellular targets, thyroid hormone must cross the plasma membrane. Because of the lipophilic nature of thyroid hormone, it was thought that they traversed the plasma membrane by simple diffusion. However, in the past decade, a membrane transport system for thyroid hormone has been postulated to exist in various tissues. Several classes of transporters, organic anion transporter polypeptide (oatp) family, Na(+)/Taurocholate cotransporting polypeptide (ntcp) and amino acid transporters have been reported to transport thyroid hormones. Monocarboxylate transporter8 (MCT8) has recently been identified as an active and specific thyroid hormone transporter. Mutations in MCT8 are associated with severe X-linked psycomotor retardation and strongly elevated serum T3 levels in young male patients. Several other molecules should be contributed to exert the role of thyroid hormone in the central nervous system.

  2. Alligators, contaminants and steroid hormones.

    PubMed

    Guillette, Louis J; Edwards, Thea M; Moore, Brandon C

    2007-01-01

    Steroids are essential for successful reproduction in all vertebrate species. Over the last several decades, extensive research has indicated that exposure to various environmental pollutants can disrupt steroidogenesis and steroid signaling. Although steroidogenesis is regulated by the hypothalamic-pituitary axis, it is also modified by various paracrine and autocrine factors. Furthermore, the classical two-cell model of steroidogenesis in the developing ovarian follicle, involving the granulosa and theca cells in mammals, may not be universal. Instead, birds and probably reptiles use the two thecal compartments (theca interna and theca externa) as sites of steroid production. We have documented that embryonic or juvenile exposure to a complex mixture of contaminants from agricultural and storm water runoff leads to altered steroid hormone profiles in American alligators. Our observations suggest that alterations in plasma steroid hormone concentrations are due in part to altered gene expression, modified hepatic biotransformation and altered gonadal steroidogenesis. Future studies must examine the interplay between endocrine and paracrine regulation in the development and expression of gonadal steroidogenesis in individuals exposed to endocrine disrupting contaminants at various life stages if we are to fully understand potential detrimental outcomes.

  3. Thyroid hormone biosynthesis and release.

    PubMed

    Carvalho, Denise P; Dupuy, Corinne

    2017-01-31

    Thyroid hormones (TH) 3,5,3',5'- tetraiodothyronine or thyroxine (T4) and 3,5,3'- triiodothyronine (T3) contain iodine atoms as part of their structure, and their synthesis occur in the unique structures called thyroid follicles. Iodide reaches thyroid cells through the bloodstream that supplies the basolateral plasma membrane of thyrocytes, where it is avidly taken up through the sodium/iodide symporter (NIS). Thyrocytes are also specialized in the secretion of the high molecular weight protein thyroglobulin (TG) in the follicular lumen. The iodination of the tyrosyl residues of TG preceeds TH biosynthesis, which depends on the interaction of iodide, TG, hydrogen peroxide (H2O2) and thyroid peroxidase (TPO) at the apical plasma membrane of thyrocytes. Thyroid hormone biosynthesis is under the tonic control of thyrotropin (TSH), while the iodide recycling ability is very important for normal thyroid function. We discuss herein the biochemical aspects of TH biosynthesis and release, highlighting the novel molecules involved in the process.

  4. Hormonal mechanisms of cooperative behaviour

    PubMed Central

    Soares, Marta C.; Bshary, Redouan; Fusani, Leonida; Goymann, Wolfgang; Hau, Michaela; Hirschenhauser, Katharina; Oliveira, Rui F.

    2010-01-01

    Research on the diversity, evolution and stability of cooperative behaviour has generated a considerable body of work. As concepts simplify the real world, theoretical solutions are typically also simple. Real behaviour, in contrast, is often much more diverse. Such diversity, which is increasingly acknowledged to help in stabilizing cooperative outcomes, warrants detailed research about the proximate mechanisms underlying decision-making. Our aim here is to focus on the potential role of neuroendocrine mechanisms on the regulation of the expression of cooperative behaviour in vertebrates. We first provide a brief introduction into the neuroendocrine basis of social behaviour. We then evaluate how hormones may influence known cognitive modules that are involved in decision-making processes that may lead to cooperative behaviour. Based on this evaluation, we will discuss specific examples of how hormones may contribute to the variability of cooperative behaviour at three different levels: (i) within an individual; (ii) between individuals and (iii) between species. We hope that these ideas spur increased research on the behavioural endocrinology of cooperation. PMID:20679116

  5. Postmenopausal hormone therapy and cognition.

    PubMed

    McCarrey, Anna C; Resnick, Susan M

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Prior to the publication of findings from the Women's Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the 'critical window hypothesis', which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as lower global cognition or diabetes. Lastly, we point towards implications for future research and clinical treatments.

  6. Hormones as doping in sports.

    PubMed

    Duntas, Leonidas H; Popovic, Vera

    2013-04-01

    Though we may still sing today, as did Pindar in his eighth Olympian Victory Ode, "… of no contest greater than Olympia, Mother of Games, gold-wreathed Olympia…", we must sadly admit that today, besides blatant over-commercialization, there is no more ominous threat to the Olympic games than doping. Drug-use methods are steadily becoming more sophisticated and ever harder to detect, increasingly demanding the use of complex analytical procedures of biotechnology and molecular medicine. Special emphasis is thus given to anabolic androgenic steroids, recombinant growth hormone and erythropoietin as well as to gene doping, the newly developed mode of hormones abuse which, for its detection, necessitates high-tech methodology but also multidisciplinary individual measures incorporating educational and psychological methods. In this Olympic year, the present review offers an update on the current technologically advanced endocrine methods of doping while outlining the latest procedures applied-including both the successes and pitfalls of proteomics and metabolomics-to detect doping while contributing to combating this scourge.

  7. Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

    ERIC Educational Resources Information Center

    Pueschel, Seigfried M.

    1993-01-01

    This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

  8. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    PubMed

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand.

  9. Collective hormonal profiles predict group performance

    PubMed Central

    Akinola, Modupe; Page-Gould, Elizabeth; Mehta, Pranjal H.; Lu, Jackson G.

    2016-01-01

    Prior research has shown that an individual’s hormonal profile can influence the individual’s social standing within a group. We introduce a different construct—a collective hormonal profile—which describes a group’s hormonal make-up. We test whether a group’s collective hormonal profile is related to its performance. Analysis of 370 individuals randomly assigned to work in 74 groups of three to six individuals revealed that group-level concentrations of testosterone and cortisol interact to predict a group’s standing across groups. Groups with a collective hormonal profile characterized by high testosterone and low cortisol exhibited the highest performance. These collective hormonal level results remained reliable when controlling for personality traits and group-level variability in hormones. These findings support the hypothesis that groups with a biological propensity toward status pursuit (high testosterone) coupled with reduced stress-axis activity (low cortisol) engage in profit-maximizing decision-making. The current work extends the dual-hormone hypothesis to the collective level and provides a neurobiological perspective on the factors that determine who rises to the top across, not just within, social hierarchies. PMID:27528679

  10. Menstrual cycle hormones, food intake, and cravings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Food craving and intake are affected by steroid hormones during the menstrual cycle, especially in the luteal phase, when craving for certain foods has been reported to increase. However, satiety hormones such as leptin have also been shown to affect taste sensitivity, and therefore food ...

  11. Insect Control (II): Hormones and Viruses

    ERIC Educational Resources Information Center

    Marx, Jean L.

    1973-01-01

    Discusses research in the use of hormones and viruses to control insect populations. Although entomologists do not think that pheromones, hormones, and viruses will completely replace more conventional chemical insecticides, they will become increasingly important and will reduce our dependence on traditional insecticides. (JR)

  12. Hormonal and Local Regulation of Bone Formation.

    ERIC Educational Resources Information Center

    Canalis, Ernesto

    1985-01-01

    Reviews effects of hormones, systemic factors, and local regulators on bone formation. Identifies and explains the impact on bone growth of several hormones as well as the components of systemic and local systems. Concentrates on bone collagen and DNA synthesis. (Physicians may earn continuing education credit by completing an appended test). (ML)

  13. The barrier within: endothelial transport of hormones.

    PubMed

    Kolka, Cathryn M; Bergman, Richard N

    2012-08-01

    Hormones are involved in a plethora of processes including development and growth, metabolism, mood, and immune responses. These essential functions are dependent on the ability of the hormone to access its target tissue. In the case of endocrine hormones that are transported through the blood, this often means that the endothelium must be crossed. Many studies have shown that the concentrations of hormones and nutrients in blood can be very different from those surrounding the cells on the tissue side of the blood vessel endothelium, suggesting that transport across this barrier can be rate limiting for hormone action. This transport can be regulated by altering the surface area of the blood vessel available for diffusion through to the underlying tissue or by the permeability of the endothelium. Many hormones are known to directly or indirectly affect the endothelial barrier, thus affecting their own distribution to their target tissues. Dysfunction of the endothelial barrier is found in many diseases, particularly those associated with the metabolic syndrome. The interrelatedness of hormones may help to explain why the cluster of diseases in the metabolic syndrome occur together so frequently and suggests that treating the endothelium may ameliorate defects in more than one disease. Here, we review the structure and function of the endothelium, its contribution to the function of hormones, and its involvement in disease.

  14. Thyroid Hormone Function in the Rat Testis

    PubMed Central

    Gao, Ying; Lee, Will M.; Cheng, C. Yan

    2014-01-01

    Thyroid hormones are emerging regulators of testicular function since Sertoli, germ, and Leydig cells are found to express thyroid hormone receptors (TRs). These testicular cells also express deiodinases, which are capable of converting the pro-hormone T4 to the active thyroid hormone T3, or inactivating T3 or T4 to a non-biologically active form. Furthermore, thyroid hormone transporters are also found in the testis. Thus, the testis is equipped with the transporters and the enzymes necessary to maintain the optimal level of thyroid hormone in the seminiferous epithelium, as well as the specific TRs to execute thyroid hormone action in response to different stages of the epithelial cycle of spermatogenesis. Studies using genetic models and/or goitrogens (e.g., propylthiouracil) have illustrated a tight physiological relationship between thyroid hormone and testicular function, in particular, Sertoli cell differentiation status, mitotic activity, gap junction function, and blood–testis barrier assembly. These findings are briefly summarized and discussed herein. PMID:25414694

  15. Minireview: Pathophysiological importance of thyroid hormone transporters.

    PubMed

    Heuer, Heike; Visser, Theo J

    2009-03-01

    Thyroid hormone metabolism and action are largely intracellular events that require transport of iodothyronines across the plasma membrane. It has been assumed for a long time that this occurs by passive diffusion, but it has become increasingly clear that cellular uptake and efflux of thyroid hormone is mediated by transporter proteins. Recently, several active and specific thyroid hormone transporters have been identified, including monocarboxylate transporter 8 (MCT8), MCT10, and organic anion transporting polypeptide 1C1 (OATP1C1). The latter is expressed predominantly in brain capillaries and transports preferentially T(4), whereas MCT8 and MCT10 are expressed in multiple tissues and are capable of transporting different iodothyronines. The pathophysiological importance of thyroid hormone transporters has been established by the demonstration of MCT8 mutations in patients with severe psychomotor retardation and elevated serum T(3) levels. MCT8 appears to play an important role in the transport of thyroid hormone in the brain, which is essential for the crucial action of the hormone during brain development. It is expected that more specific thyroid hormone transporters will be discovered in the near future, which will lead to a better understanding of the tissue-specific regulation of thyroid hormone bioavailability.

  16. Recombinant Bovine Growth Hormone Criticism Grows.

    ERIC Educational Resources Information Center

    Gaard, Greta

    1995-01-01

    Discusses concerns related to the use of recombinant bovine growth hormone in the United States and other countries. Analyses the issue from the perspectives of animal rights, human health, world hunger, concerns of small and organic farmers, costs to the taxpayer, and environmental questions. A sidebar discusses Canadian review of the hormone.…

  17. Ubiquitin, Hormones and Biotic Stress in Plants

    PubMed Central

    Dreher, Kate; Callis, Judy

    2007-01-01

    Background The covalent attachment of ubiquitin to a substrate protein changes its fate. Notably, proteins typically tagged with a lysine48-linked polyubiquitin chain become substrates for degradation by the 26S proteasome. In recent years many experiments have been performed to characterize the proteins involved in the ubiquitylation process and to identify their substrates, in order to understand better the mechanisms that link specific protein degradation events to regulation of plant growth and development. Scope This review focuses on the role that ubiquitin plays in hormone synthesis, hormonal signalling cascades and plant defence mechanisms. Several examples are given of how targeted degradation of proteins affects downstream transcriptional regulation of hormone-responsive genes in the auxin, gibberellin, abscisic acid, ethylene and jasmonate signalling pathways. Additional experiments suggest that ubiquitin-mediated proteolysis may also act upstream of the hormonal signalling cascades by regulating hormone biosynthesis, transport and perception. Moreover, several experiments demonstrate that hormonal cross-talk can occur at the level of proteolysis. The more recently established role of the ubiquitin/proteasome system (UPS) in defence against biotic threats is also reviewed. Conclusions The UPS has been implicated in the regulation of almost every developmental process in plants, from embryogenesis to floral organ production probably through its central role in many hormone pathways. More recent evidence provides molecular mechanisms for hormonal cross-talk and links the UPS system to biotic defence responses. PMID:17220175

  18. Juvenile hormone regulation of Drosophila aging

    PubMed Central

    2013-01-01

    Background Juvenile hormone (JH) has been demonstrated to control adult lifespan in a number of non-model insects where surgical removal of the corpora allata eliminates the hormone’s source. In contrast, little is known about how juvenile hormone affects adult Drosophila melanogaster. Previous work suggests that insulin signaling may modulate Drosophila aging in part through its impact on juvenile hormone titer, but no data yet address whether reduction of juvenile hormone is sufficient to control Drosophila life span. Here we adapt a genetic approach to knock out the corpora allata in adult Drosophila melanogaster and characterize adult life history phenotypes produced by reduction of juvenile hormone. With this system we test potential explanations for how juvenile hormone modulates aging. Results A tissue specific driver inducing an inhibitor of a protein phosphatase was used to ablate the corpora allata while permitting normal development of adult flies. Corpora allata knockout adults had greatly reduced fecundity, inhibited oogenesis, impaired adult fat body development and extended lifespan. Treating these adults with the juvenile hormone analog methoprene restored all traits toward wildtype. Knockout females remained relatively long-lived even when crossed into a genotype that blocked all egg production. Dietary restriction further extended the lifespan of knockout females. In an analysis of expression profiles of knockout females in fertile and sterile backgrounds, about 100 genes changed in response to loss of juvenile hormone independent of reproductive state. Conclusions Reduced juvenile hormone alone is sufficient to extend the lifespan of Drosophila melanogaster. Reduced juvenile hormone limits reproduction by inhibiting the production of yolked eggs, and this may arise because juvenile hormone is required for the post-eclosion development of the vitellogenin-producing adult fat body. Our data do not support a mechanism for juvenile hormone control

  19. Hormones and pheromones in regulation of insect behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Both pheromones and hormones are well recognized regulators of insect biology. However, the interactions between hormones and pheromones in coordinating insect biology are less well understood. We have studied the interactions between juvenile hormone, its precursor methyl farnesoate, and pheromon...

  20. Combined Hormonal Birth Control: Pill, Patch, and Ring

    MedlinePlus

    ... FREQUENTLY ASKED QUESTIONS FAQ185 CONTRACEPTION Combined Hormonal Birth Control: Pill, Patch, and Ring • What are combined hormonal birth control methods? • How do combined hormonal methods prevent pregnancy? • ...

  1. Thyroid hormone and the growth plate.

    PubMed

    Shao, Yvonne Y; Wang, Lai; Ballock, R Tracy

    2006-12-01

    Thyroid hormone was first identified as a potent regulator of skeletal maturation at the growth plate more than forty years ago. Since that time, many in vitro and in vivo studies have confirmed that thyroid hormone regulates the critical transition between cell proliferation and terminal differentiation in the growth plate, specifically the maturation of growth plate chondrocytes into hypertrophic cells. However these studies have neither identified the molecular mechanisms involved in the regulation of skeletal maturation by thyroid hormone, nor demonstrated how the systemic actions of thyroid hormone interface with the local regulatory milieu of the growth plate. This article will review our current understanding of the role of thyroid hormone in regulating the process of endochondral ossification at the growth plate, as well as what is currently known about the molecular mechanisms involved in this regulation.

  2. Parathyroid Hormone, Calcitonin, and Vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T.

    1972-01-01

    Analyses of secretion of parathyroid hormone during tests of stimulation and suppression of hormone-secretory activity using infusions of EDTA and calcium, respectively, have established that, in contrast to previous views, secretion of the hormone is not autonomous in many patients that have adenomatous hyperparathyroidism, but is responsive to changes in blood-calcium concentration. These findings have led to a new understanding of the pathophysiology of hormone production in hyperparathy-roidism. A related application of the diagnostic use of the radioimmunoassay is the preoperative localization of parathyroid tumors and the distinction between adenomas and chief-cell hyperplasia. Work involving catheterization and radioimmunoassay of blood samples obtained from the subclavin and innominate veins and the venae cavae, led to localization in a high percentage of patients. However, this procedure has been adopted recently to detect hormone concentration in the small veins directly draining the parathyroid glands.

  3. Hormone activation induces nucleosome positioning in vivo

    PubMed Central

    Belikov, Sergey; Gelius, Birgitta; Almouzni, Geneviève; Wrange, Örjan

    2000-01-01

    The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the transition in chromatin structure following hormone activation. This revealed two novel findings: hormone activation led to the establishment of specific translational positioning of nucleosomes despite the lack of significant positioning in the inactive state; and, in the active promoter, a subnucleosomal particle encompassing the glucocorticoid receptor (GR)-binding region was detected. The presence of only a single GR-binding site was sufficient for the structural transition to occur. Both basal promoter elements and ongoing transcription were dispensable. These data reveal a stepwise process in the transcriptional activation by glucocorticoid hormone. PMID:10698943

  4. [Plant hormones, plant growth regulators].

    PubMed

    Végvári, György; Vidéki, Edina

    2014-06-29

    Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life.

  5. Hormonal changes in antiorthostatic rats

    NASA Technical Reports Server (NTRS)

    Popovic, V.; Popovic, P.; Honeycutt, C.

    1982-01-01

    Hypokinesia, especially hypokinesia with negative tilt ('antiorthostatic hypokinesia'), mimics some of the effects of weightlessness. It is shown that cardiac output is increased during early exposure of rats to antiorthostatic hypokinesia. The increase of the stroke volume and of the cardiac output observed in the antiorthostatic hypokinetic rats is probably the consequence of a blood volume shift toward the chest brought forth by head-down positioning of the animals. It is also possible that struggling of the animals to escape from the harness and an increased metabolism contribute to the elevation of cardiac output. In order to study this hypothesis 'stress hormones' were measured in the antiorthostatic rats. Plasma levels of ACTH, corticosterone and prolactin were measured in the arterial blood (0.3 ml) sampled before, during and after hypokinesia from chronic aortic cannulas of the rats.

  6. Growth hormone and physical performance.

    PubMed

    Birzniece, Vita; Nelson, Anne E; Ho, Ken K Y

    2011-05-01

    There has been limited research and evidence that GH enhances physical performance in healthy adults or in trained athletes. Even so, human growth hormone (GH) is widely abused by athletes. In healthy adults, GH increases lean body mass, although it is possible that fluid retention contributes to this effect. The most recent data indicate that GH does not enhance muscle strength, power, or aerobic exercise capacity, but improves anaerobic exercise capacity. In fact, there are adverse effects of long-term GH excess such that sustained abuse of GH can lead to a state mimicking acromegaly, a condition with increased morbidity and mortality. This review will examine GH effects on body composition and physical performance in health and disease.

  7. Nuclear hormone receptors in chordates.

    PubMed

    Bertrand, Stéphanie; Belgacem, Mohamed R; Escriva, Hector

    2011-03-01

    In order to understand evolution of the endocrine systems in chordates, study of the evolution of the nuclear receptors (NRs), which mediate the cellular responses to several key hormones, is of major interest. Thanks to the sequencing of several complete genomes of different species in the three chordate phyla, we now have a global view of the evolution of the nuclear receptors gene content in this lineage. The challenge is now to understand how the function of the different receptors evolved during the invertebrate-chordate to vertebrate transition by studying the functional properties of the NRs using comparative approaches in different species. The best available model system to answer this question is the cephalochordate amphioxus which has a NR gene complement close to that of the chordate ancestor. Here we review the available data concerning the function of the amphioxus NRs, and we discuss some evolutionary scenarios that can be drawn from these results.

  8. Hormonal contraception in the male.

    PubMed

    Anderson, R A

    2000-01-01

    The hormonal approach to male contraception is based on the suppression of gonadotrophin secretion with secondary suppression of spermatogenesis. This can be achieved by administration of testosterone or other androgen alone, but combined administration with a progestogen or GnRH analogue allows the dose of testosterone to be reduced to physiological replacement doses. This approach has been investigated for many years but without identification of a regimen which results in sufficient suppression of spermatogenesis to provide ensured contraception in all men, safely and conveniently. The reasons for this are discussed, and recent developments towards a regimen that fulfills all these criteria are described. Crucial to development of any new product is that it will be used: surveys of both men and women indicate firmly positive attitudes towards a 'male pill'. There are, therefore, grounds for cautious optimism that the next decade may see the introduction of the first novel male contraceptive for several hundred years.

  9. Thyroid hormones and heart failure.

    PubMed

    Martinez, Felipe

    2016-07-01

    Heart failure is a major health problem and its relationship to thyroid dysfunction has been increasingly investigated in recent years. Since it has been demonstrated that thyroid hormones (TH) and mainly T3 have cardioprotective effects, it is easy to understand that in the scenario of thyroid disorder, cardiac function may be damaged, and inversely in cardiac dysfunction thyroid dysregulation may be seen. The increase in plasma TH produces a clear neurohormonal activation which impacts negatively on cardiac function. In hypothyroidism, and in addition to extracardiac dysfunction, myocardial and vascular remodelling is altered and they contribute to cardiac failure. Abnormal low plasma TSH has also been shown to be a risk factor for developing HF in several recent studies, and they suggest that TSH is an independent predictor of clinical outcome including death and cardiac hospitalizations. Therefore, physicians should consider all these concepts when managing a patient with heart failure, not only for a clear diagnosis, but also for better and accurate treatment.

  10. [Rational hormonal diagnosis of oligomenorrhea].

    PubMed

    Weise, H C; Moltz, L; Bispink, G; Leidenberger, F

    1989-08-01

    In a study, conducted by two clinics in Berlin and Hamburg, specializing in reproductive endocrinology, the anamnestic, clinical, and laboratory data of 170 oligomenorrheic patients (menstrual intervals between 35 and 90 days) were evaluated in order to determine the frequency of possible causes of oligomenorrhea. Pathological hormone levels were found in two thirds of all patients. The order of frequency of abnormal hormone levels was as follows: hyperandrogenemia (testosterone and/or DHEA-sulfate) in 41.8%, hyperprolactinemia in 25.9%, abnormal thyroid function (TSH and/or TRH-induced TSH) in 21.7%, and hypergonadotropic FSH levels in 3.5% of all patients. There was an overlap of between two or more pathological conditions in one third of all patients. This study confirms results of a previous study in amenorrheic patients (Moltz et al., 1987 - see reference list), documenting hyperandrogenemia as the most frequent abnormality found in this group, followed by hyperprolactinemia. As can be expected, the percentage of women with no discernible abnormality was higher in oligomenorrheic patients when compared with the amenorrheic group (32.3% vs 7.7%). Furthermore, overweight patients were overrepresented in the oligomenorrheic group, while underweight patients were seen more frequently in the amenorrheic group. In view of these results of our study we recommend a detailed diagnostic follow-up in all younger patients with ovarian disorders who need to preserve their reproductive potential. This follow-up should include hyperprolactinemia, hypo-/hyperthyroidism, hyperandrogenemic and hypoestrogenemic states and exclusion of primary ovarian failure. In contrast to recommendations of WHO, issued in 1976, such diagnostic work allows an etiology oriented therapy decision and a therapy risk assessment in subgroups of patients, such as hyperandrogenemic patients, who receive clomiphene or gonadotropin treatment. Furthermore, it permits prophylactic considerations, for

  11. Adipose tissues and thyroid hormones

    PubMed Central

    Obregon, Maria-Jesus

    2014-01-01

    The maintenance of energy balance is regulated by complex homeostatic mechanisms, including those emanating from adipose tissue. The main function of the adipose tissue is to store the excess of metabolic energy in the form of fat. The energy stored as fat can be mobilized during periods of energy deprivation (hunger, fasting, diseases). The adipose tissue has also a homeostatic role regulating energy balance and functioning as endocrine organ that secretes substances that control body homeostasis. Two adipose tissues have been identified: white and brown adipose tissues (WAT and BAT) with different phenotype, function and regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and white adipocytes have different ontogenetic origin and lineage and specific markers of WAT and BAT have been identified. “Brite” or beige adipose tissue has been identified in WAT with some properties of BAT. Thyroid hormones exert pleiotropic actions, regulating the differentiation process in many tissues including the adipose tissue. Adipogenesis gives raise to mature adipocytes and is regulated by several transcription factors (c/EBPs, PPARs) that coordinately activate specific genes, resulting in the adipocyte phenotype. T3 regulates several genes involved in lipid mobilization and storage and in thermogenesis. Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial function, transcription factors, the availability of nutrients. T3 acts directly through specific TREs in the gene promoters, regulating transcription factors. The deiodinases D3, D2, and D1 regulate the availability of T3. D3 is activated during proliferation, while D2 is linked to the adipocyte differentiation program, providing T3 needed for lipogenesis and thermogenesis. We examine the differences between BAT, WAT and brite/beige adipocytes and the process that lead to activation of UCP1 in WAT

  12. Sexual Desire and Hormonal Contraception

    PubMed Central

    Boozalis, Amanda; Tutlam, Nhial T.; Robbins, Camaryn Chrisman; Peipert, Jeffrey F.

    2015-01-01

    Objective To examine the effect of hormonal contraception on sexual desire. Materials and Methods We performed a cross-sectional analysis of 1,938 of the 9,256 participants enrolled in the Contraceptive CHOICE Project. This subset included participants enrolled between April and September 2011 who completed a baseline and six-month telephone survey. Multivariable logistic regression was used to assess the association between contraceptive method and report of lacking interest in sex, controlling for potential confounding variables. Results More than one in five participants (23.9%) reported lacking interest in sex at 6 months after initiating a new contraceptive method. Of 262 copper IUD users (referent group), 18.3% reported lacking interest in sex. Our primary outcome was more prevalent in women who are young (<18 years: adjusted odds ratio (ORadj)=2.04), black (ORadj=1.78), and married or living with a partner (ORadj=1.82). Compared to copper IUD users, participants using depot medroxyprogesterone (ORadj=2.61, 95% confidence interval (CI)=1.47-4.61), the vaginal ring (ORadj=2.53, 95% CI=1.37-4.69), and the implant (ORadj=1.60, 95% CI=1.03-2.49) more commonly reported lack of interest in sex. We found no association between use of the hormonal IUD, oral contraceptive pill, and patch and lack of interest in sex. Conclusion CHOICE participants using depot medroxyprogesterone acetate, the contraceptive ring, and implant were more likely to report a lack of interest in sex compared to copper IUD users. Future research should confirm these findings and their possible physiological basis. Clinicians should be reassured that most women do not experience reduced sex drive with the use of most contraceptive methods. PMID:26855094

  13. A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice

    PubMed Central

    Aiba, Yuji; Nakano, Yasuhiro; Koga, Yasuhiro; Takahashi, Kenji; Komatsu, Yasuhiko

    2015-01-01

    A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori,Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii,JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI. PMID:25771812

  14. The revolution in insect neuropeptides illustrated by the adipokinetic hormone/red pigment-concentrating hormone family of peptides.

    PubMed

    Gäde, G

    1996-01-01

    The last decade has seen a surge in the knowledge on primary structures of insect neuropeptides. Particularly successful were isolations and sequence determinations of more than 30 members of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. This brief overview describes the techniques used to obtain data on purification and structure such as high performance liquid chromatography, Edman sequencing and mass spectrometry. Moreover, a short account on the precursors and on the multiple functions of the peptides of the AKH/RPCH family in various crustacean and insect species is given.

  15. Effects of hormones on lipids and lipoproteins

    SciTech Connect

    Krauss, R.M.

    1991-12-01

    Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men and are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.

  16. Hormonal modulation of endothelial NO production.

    PubMed

    Duckles, Sue P; Miller, Virginia M

    2010-05-01

    Since the discovery of endothelium-derived relaxing factor and the subsequent identification of nitric oxide (NO) as the primary mediator of endothelium-dependent relaxations, research has focused on chemical and physical stimuli that modulate NO levels. Hormones represent a class of soluble, widely circulating chemical factors that impact production of NO both by rapid effects on the activity of endothelial nitric oxide synthase (eNOS) through phosphorylation of the enzyme and longer term modulation through changes in amount of eNOS protein. Hormones that increase NO production including estrogen, progesterone, insulin, and growth hormone do so through both of these common mechanisms. In contrast, some hormones, including glucocorticoids, progesterone, and prolactin, decrease NO bioavailability. Mechanisms involved include binding to repressor response elements on the eNOS gene, competing for co-regulators common to hormones with positive genomic actions, regulating eNOS co-factors, decreasing substrate for eNOS, and increasing production of oxygen-derived free radicals. Feedback regulation by the hormones themselves as well as the ability of NO to regulate hormonal release provides a second level of complexity that can also contribute to changes in NO levels. These effects on eNOS and changes in NO production may contribute to variability in risk factors, presentation of and treatment for cardiovascular disease associated with aging, pregnancy, stress, and metabolic disorders in men and women.

  17. Hormonal Factors and Disturbances in Eating Disorders.

    PubMed

    Culbert, Kristen M; Racine, Sarah E; Klump, Kelly L

    2016-07-01

    This review summarizes the current state of the literature regarding hormonal correlates of, and etiologic influences on, eating pathology. Several hormones (e.g., ghrelin, CCK, GLP-1, PYY, leptin, oxytocin, cortisol) are disrupted during the ill state of eating disorders and likely contribute to the maintenance of core symptoms (e.g., dietary restriction, binge eating) and/or co-occurring features (e.g., mood symptoms, attentional biases). Some of these hormones (e.g., ghrelin, cortisol) may also be related to eating pathology via links with psychological stress. Despite these effects, the role of hormonal factors in the etiology of eating disorders remains unknown. The strongest evidence for etiologic effects has emerged for ovarian hormones, as changes in ovarian hormones predict changes in phenotypic and genetic influences on disordered eating. Future studies would benefit from utilizing etiologically informative designs (e.g., high risk, behavioral genetic) and continuing to explore factors (e.g., psychological, neural responsivity) that may impact hormonal influences on eating pathology.

  18. Arabidopsis Hormone Database: a comprehensive genetic and phenotypic information database for plant hormone research in Arabidopsis.

    PubMed

    Peng, Zhi-yu; Zhou, Xin; Li, Linchuan; Yu, Xiangchun; Li, Hongjiang; Jiang, Zhiqiang; Cao, Guangyu; Bai, Mingyi; Wang, Xingchun; Jiang, Caifu; Lu, Haibin; Hou, Xianhui; Qu, Lijia; Wang, Zhiyong; Zuo, Jianru; Fu, Xiangdong; Su, Zhen; Li, Songgang; Guo, Hongwei

    2009-01-01

    Plant hormones are small organic molecules that influence almost every aspect of plant growth and development. Genetic and molecular studies have revealed a large number of genes that are involved in responses to numerous plant hormones, including auxin, gibberellin, cytokinin, abscisic acid, ethylene, jasmonic acid, salicylic acid, and brassinosteroid. Here, we develop an Arabidopsis hormone database, which aims to provide a systematic and comprehensive view of genes participating in plant hormonal regulation, as well as morphological phenotypes controlled by plant hormones. Based on data from mutant studies, transgenic analysis and gene ontology (GO) annotation, we have identified a total of 1026 genes in the Arabidopsis genome that participate in plant hormone functions. Meanwhile, a phenotype ontology is developed to precisely describe myriad hormone-regulated morphological processes with standardized vocabularies. A web interface (http://ahd.cbi.pku.edu.cn) would allow users to quickly get access to information about these hormone-related genes, including sequences, functional category, mutant information, phenotypic description, microarray data and linked publications. Several applications of this database in studying plant hormonal regulation and hormone cross-talk will be presented and discussed.

  19. Obtaining growth hormone from calf blood

    NASA Technical Reports Server (NTRS)

    Kalchev, L. A.; Ralchev, K. K.; Nikolov, I. T.

    1979-01-01

    The preparation of a growth hormone from human serum was used for the isolation of the hormone from calf serum. The preparation was biologically active - it increased the quantity of the free fatty acids released in rat plasma by 36.4 percent. Electrophoresis in Veronal buffer, ph 8.6, showed the presence of a single fraction having mobility intermediate between that of alpha and beta globulins. Gel filtration through Sephadex G 100 showed an elutriation curve identical to that obtained by the growth hormone prepared from pituitary glands.

  20. Hormonal component of tumor photodynamic therapy response

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush

    2008-02-01

    The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

  1. A Hormonally Active Malignant Struma Ovarii

    PubMed Central

    Lara, Carolina; Salame, Latife; Padilla-Longoria, Rafael

    2016-01-01

    Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii. PMID:27882257

  2. The Radioimmunoassay of Fluid and Electrolyte Hormones

    NASA Technical Reports Server (NTRS)

    Keil, Lanny C.

    1985-01-01

    The subject of the paper will be the assay of fluid/electrolyte hormones. ADH (antidiuretic hormone also referred to as vasopressin) reduces fluid loss by increasing water reabsorption by the kidney. The stimuli for its release from the pituitary are loss of blood, dehydration, or increased salt intake. Angiotensin II is the next hormone of interest. It is "generated" from a blood protein by the release of renin from the kidney. One of its functions is to stimulate the secretion of aldosterone from the adrenal gland. Release of renin is also stimulated by volume and sodium loss.

  3. Sleep and hormonal changes in aging.

    PubMed

    Copinschi, Georges; Caufriez, Anne

    2013-06-01

    Age-related sleep and endocrinometabolic alterations frequently interact with each other. For many hormones, sleep curtailment in young healthy subjects results in alterations strikingly similar to those observed in healthy old subjects not submitted to sleep restriction. Thus, recurrent sleep restriction, which is currently experienced by a substantial and rapidly growing proportion of children and young adults, might contribute to accelerate the senescence of endocrine and metabolic function. The mechanisms of sleep-hormonal interactions, and therefore the endocrinometabolic consequences of age-related sleep alterations, which markedly differ from one hormone to another, are reviewed in this article.

  4. Effects of ghrelin, growth hormone-releasing peptide-6, and growth hormone-releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus.

    PubMed

    de Sá, Larissa Bianca Paiva Cunha; Nascif, Sergio Oliva; Correa-Silva, Silvia Regina; Molica, Patricia; Vieira, José Gilberto Henriques; Dib, Sergio Atala; Lengyel, Ana-Maria Judith

    2010-10-01

    In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide-6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)-induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend (P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.

  5. History of growth hormone therapy.

    PubMed

    Blizzard, Robert M

    2012-01-01

    The first human to receive GH therapy was in 1956; it was of bovine origin and was given for 3 wk for metabolic balance studies revealing no effects. By 1958, three separate laboratories utilizing different extraction methods retrieved hGH from human pituitaries, purified it and used for clinical investigation. By 1959 presumed GHD patients were being given native hGH collected and extracted by various methods. Since 1 mg of hGH was needed to treat one patient per day, >360 human pituitaries were needed per patient per year. Thus, the availability of hGH was limited and was awarded on the basis of clinical research protocols approved by the National Pituitary Agency (NPA) established in 1961. hGH was dispensed and injected on a milligram weight basis with varied concentrations between batches from 0.5 units/mg to 2.0 units/mg of hGH. By 1977 a centralized laboratory was established to extract all human pituitaries in the US, this markedly improved the yield of hGH obtained and most remarkably, hGH of this laboratory was never associated with Creutzfeld-Jacob disease (CJD) resulting from the injection of apparently prior- contaminated hGH produced years earlier. However, widespread rhGH use was not possible even if a pituitary from each autopsy performed in the US was collected, this would only permit therapy for about 4,000 patients. Thus, the mass production of rhGH required the identification of the gene structure of the hormone, methodology that began in 1976 to make insulin by recombinant technology. Serendipity was manifest in 1985 when patients who had received hGH years previously were reported to have died of CJD. This led to the discontinuation of the distribution and use of hGH, at a time when a synthetic rhGH became available for clinical use. The creation of a synthetic rhGH was accompanied by unlimited supplies of hGH for investigation and therapy. However, the appropriate use and the potential abuse of this hormone are to be dealt with. The

  6. Quo vadis neurohypophysial hormone research?

    PubMed

    Douglas, A J; Ludwig, M

    2000-03-01

    Here we highlight just a few of the outstanding questions in the field of neurohypophysial hormones that we envisage will be addressed successfully in the new millennium. To begin, we focus on the regulation of receptors. Despite intensive investigation with new drugs, molecular modelling and transgenic models, the determinants of receptor selectivity remain elusive; there may even be more vasopressin or oxytocin receptor subtypes to be discovered. We discuss the controversy over the interesting studies that indicate modulation of oxytocin receptor-binding by steroids. Oxytocin and vasopressin release and action in the brain are discussed from several aspects. Dendritically released oxytocin acting locally is important for the milk ejection reflex, and similarly released vasopressin is important in regulating patterning of vasopressin neurone activity. Such dendritically released oxytocin and vasopressin is likely to be important in paracrine modulation of neural circuitry involved in neuroendocrine control, and for a range of behaviours. Is it possible that the whole range of behaviours that comprise 'social' (or 'anti-social') or 'maternal' behaviour can be engineered by modifying the expression of just these one or two peptides and their receptors? However, whether gene expression and knockout approaches will answer all the open questions about the real functions of oxytocin and vasopressin remains to be shown.

  7. Parathyroid hormone and bone healing.

    PubMed

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-07-01

    Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

  8. Neuroendocrine hormone amylin in diabetes

    PubMed Central

    Zhang, Xiao-Xi; Pan, Yan-Hong; Huang, Yan-Mei; Zhao, Hai-Lu

    2016-01-01

    The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and co-secreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, amylin reduces secretion of nutrient-stimulated glucagon, regulates blood pressure with an effect on renin-angiotensin system, and delays gastric emptying. The physiological actions of human amylin attribute to the conformational α-helix monomers whereas the misfolding instable oligomers may be detrimental to the islet β cells and further transform to β-sheet fibrils as amyloid deposits. No direct evidence proves that the amylin fibrils in amyloid deposits cause diabetes. Here we also have performed a systematic review of human amylin gene changes and reported the S20G mutation is minor in the development of diabetes. In addition to the metabolic effects, human amylin may modulate autoimmunity and innate inflammation through regulatory T cells to impact on both human type 1 and type 2 diabetes. PMID:27162583

  9. Thyroid Hormone and Seasonal Rhythmicity

    PubMed Central

    Dardente, Hugues; Hazlerigg, David G.; Ebling, Francis J. P.

    2014-01-01

    Living organisms show seasonality in a wide array of functions such as reproduction, fattening, hibernation, and migration. At temperate latitudes, changes in photoperiod maintain the alignment of annual rhythms with predictable changes in the environment. The appropriate physiological response to changing photoperiod in mammals requires retinal detection of light and pineal secretion of melatonin, but extraretinal detection of light occurs in birds. A common mechanism across all vertebrates is that these photoperiod-regulated systems alter hypothalamic thyroid hormone (TH) conversion. Here, we review the evidence that a circadian clock within the pars tuberalis of the adenohypophysis links photoperiod decoding to local changes of TH signaling within the medio-basal hypothalamus (MBH) through a conserved thyrotropin/deiodinase axis. We also focus on recent findings which indicate that, beyond the photoperiodic control of its conversion, TH might also be involved in longer-term timing processes of seasonal programs. Finally, we examine the potential implication of kisspeptin and RFRP3, two RF-amide peptides expressed within the MBH, in seasonal rhythmicity. PMID:24616714

  10. Hormonal regulation of energy partitioning.

    PubMed

    Rohner-Jeanrenaud, F

    2000-06-01

    A loop system exists between hypothalamic neuropeptide Y (NPY) and peripheral adipose tissue leptin to maintain normal body homeostasis. When hypothalamic NPY levels are increased by fasting or by intracerebroventricular (i.c.v.) infusion, food intake and body weight increase. NPY has genuine hormono-metabolic effects. It increases insulin and corticosterone secretion relative to controls. These hormonal changes, acting singly or combined, favor adipose tissue lipogenic activity, while producing muscle insulin resistance. They also promote leptin release from adipose tissue. When infused i.c.v. to normal rats to mimic its central effects, leptin decreases NPY levels, thus food intake and body weight. Leptin i.c.v. has also genuine hormono-metabolic effects. It decreases insulinemia and adipose tissue storage ability, enhancing glucose disposal. Leptin increases the expression of uncoupling proteins (UCP-1, -2, -3) and thus energy dissipation. Leptin-induced changes favor oxidation at the expense of storage. Circadian fluctuations of NPY and leptin levels maintain normal body homeostasis. In animal obesity, defective hypothalamic leptin receptor activation prevent leptin from acting, with resulting obesity, insulin and leptin resistance.

  11. Extrapituitary growth hormone and growth?

    PubMed

    Harvey, Steve; Baudet, Marie-Laure

    2014-09-01

    While growth hormone (GH) is obligatory for postnatal growth, it is not required for a number of growth-without-GH syndromes, such as early embryonic or fetal growth. Instead, these syndromes are thought to be dependent upon local growth factors, rather than pituitary GH. The GH gene is, however, also expressed in many extrapituitary tissues, particularly during early development and extrapituitary GH may be one of the local growth factors responsible for embryonic or fetal growth. Moreover, as the expression of the GH receptor (GHR) gene mirrors that of GH in extrapituitary tissues the actions of GH in early development are likely to be mediated by local autocrine or paracrine mechanisms, especially as extrapituitary GH expression occurs prior to the ontogeny of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of GH in embryos has also been shown to be of functional relevance in a number of species, since the immunoneutralization of endogenous GH or the blockade of GH production is accompanied by growth impairment or cellular apoptosis. The extrapituitary expression of the GH gene also persists in some central and peripheral tissues postnatally, which may reflect its continued functional importance and physiological or pathophysiological significance. The expression and functional relevance of extrapituitary GH, particularly during embryonic growth, is the focus of this brief review.

  12. Chemosignals, hormones, and amphibian reproduction.

    PubMed

    Woodley, Sarah

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". Amphibians are often thought of as relatively simple animals especially when compared to mammals. Yet the chemosignaling systems used by amphibians are varied and complex. Amphibian chemosignals are particularly important in reproduction, in both aquatic and terrestrial environments. Chemosignaling is most evident in salamanders and newts, but increasing evidence indicates that chemical communication facilitates reproduction in frogs and toads as well. Reproductive hormones shape the production, dissemination, detection, and responsiveness to chemosignals. A large variety of chemosignals have been identified, ranging from simple, invariant chemosignals to complex, variable blends of chemosignals. Although some chemosignals elicit straightforward responses, others have relatively subtle effects. Review of amphibian chemosignaling reveals a number of issues to be resolved, including: 1) the significance of the complex, individually variable blends of courtship chemosignals found in some salamanders, 2) the behavioral and/or physiological functions of chemosignals found in anuran "breeding glands", 3) the ligands for amphibian V2Rs, especially V2Rs expressed in the main olfactory epithelium, and 4) the mechanism whereby transdermal delivery of chemosignals influences behavior. To date, only a handful of the more than 7000 species of amphibians has been examined. Further study of amphibians should provide additional insight to the role of chemosignals in reproduction.

  13. Thyroid hormones and renin secretion.

    PubMed

    Ganong, W F

    Circulating angiotensin is produced by the action of renin from the kidneys on circulating angiotensinogen. There are other renin-angiotensin systems in various organs in the body, and recent observations raise the intriguing possibility that angiotensin II is produced by a totally intracellular pathway in the juxtaglomerular cells, the gonadotrops of the anterior pituitary, neurons, in the brain, salivary duct cells, and neuroblastoma cells. Circulating angiotensin II levels depend in large part on the plasma concentration of angiotensinogen, which is hormonally regulated, and on the rate of renin secretion. Renin secretion is regulated by an intrarenal baroreceptor mechanism, a macula densa mechanism, angiotensin II, vasopressin, and the sympathetic nervous system. The increase in renin secretion produced by sympathetic discharge is mediated for the most part by beta-adrenergic receptors, which are probably located on the juxtaglomerular cells. Hyperthyroidism would be expected to be associated with increased renin secretion in view of the increased beta-adrenergic activity in this condition, and hypothyroidism would be associated with decreased plasma renin activity due to decreased beta-adrenergic activity. Our recent research on serotonin-mediated increases in renin secretion that depend on the integrity of the dorsal raphe nucleus and the mediobasal hypothalamus has led us to investigate the effect of the pituitary on the renin response to p-chloroamphetamine. The response is potentiated immediately after hypophysectomy, but 22 days after the operation, it is abolished. This slowly developing decrease in responsiveness may be due to decreased thyroid function.

  14. Management of Hormone Deprivation Symptoms After Cancer.

    PubMed

    Faubion, Stephanie S; Loprinzi, Charles L; Ruddy, Kathryn J

    2016-08-01

    Cancer survivors often experience symptoms related to hormone deprivation, including vasomotor symptoms, genitourinary symptoms, and sexual health concerns. These symptoms can occur due to natural menopause in midlife women, or they can be brought on by oncologic therapies in younger women or men. We searched PubMed for English-language studies from January 1990 through January 2016 to identify relevant articles on the management of hormone deprivation symptoms, including vasomotor, genitourinary, and sexual symptoms in patients with cancer. The search terms used included hormone deprivation, vasomotor symptoms, hot flash, vaginal dryness, sexual dysfunction, and breast cancer. This manuscript provides a comprehensive description of data supporting the treatment of symptoms associated with hormone deprivation.

  15. Strategies for the Determination of Plant Hormones.

    ERIC Educational Resources Information Center

    Davis, Gregory C.; And Others

    1985-01-01

    Describes methods for isolating, purifying, and analyzing plant hormones (molecules involved in plant growth regulation and development). The presentation reflects the historical development of analyses, beginning with bioassays and ending with novel immunochemical assays. (JN)

  16. [Hormonal stimulation of reproductive function in swine].

    PubMed

    Hladkova, A I

    1993-01-01

    Industrial conditions, gynaecological disorders, ovarian deficiency being unfavourable factors for pigs reproduction, as well as the necessity in rapid sex maturation require thorough knowledge on physiology of reproduction processes. The importance belongs to the hormonal treatment in development of special biotechnological methods. Efficiency of the latter is determined by the kind of hormone used, its dose, injection time in sex cycle and the knowledge of species specificity of physiological regulation of reproductive processes in pigs of great value. The achievements in this country and abroad, devoted to the technology of oestrogens, gestagens, androgens and their combinations as well as gonadotropins (PMS, CG), gonadotropin-releasing hormone applications have been reviewed. The most often used schemes of hormonal treatment and drugs, as well as the results obtained have been described. The data presented can be used for needs of practical cattle-breeding.

  17. Gut hormones: the future of obesity treatment?

    PubMed Central

    McGavigan, Anne K; Murphy, Kevin G

    2012-01-01

    Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. PMID:22452339

  18. [Lysosomal system in hormonal mechanisms. Review].

    PubMed

    Duran Reyes, G; González Macías, G; Hicks, J J

    1995-02-01

    The role of lysosomes in the intracellular mechanism of action of several steroid an proteic hormones has been demonstrated. In presence of the specific hormone the target cell induce membranal changes and the lysosomes are moved toward the nucleus; after this the lysosomal enzymes are released in the perinuclear space. For the moment it is not possible to know the biochemical role of this enzymatic activities upon the nucleic acids function and des-repretion process of specific genes, but the inhibition of lysosomes movement utilizing hormone antagonist or dexamethasone inhibits some reproductive process like the implantation of the mammalian egg. We present herein a review related with the mode action of some hormones through the lysosomes in reproductive processes.

  19. IODIDE DEFICIENCY, THYROID HORMONES, AND NEURODEVELOPMENT

    EPA Science Inventory

    ABSTRACT BODY: Iodide is an essential nutrient for thyroid hormone synthesis. Severe iodide insufficiency during early development is associated with cognitive deficits. Environmental contaminants can perturb the thyroid axis and this perturbation may be more acute under conditio...

  20. Growth hormone replacement therapy in Costello syndrome.

    PubMed

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  1. Hormonal and biochemical responses to transcendental meditation.

    PubMed Central

    Cooper, R.; Joffe, B. I.; Lamprey, J. M.; Botha, A.; Shires, R.; Baker, S. G.; Seftel, H. C.

    1985-01-01

    This study was designed to assess whether transcendental meditation (TM) could influence various endocrine responses in 10 experienced male meditators. Nine matched subjects, uninformed of the TM procedure, acted as controls. Meditators successfully practised their technique for 40 min in the morning while controls relaxed for this period. No significant differences emerged between these 2 groups with respect to carbohydrate metabolism (plasma glucose, insulin and pancreatic glucagon concentrations), pituitary hormones (growth hormone and prolactin) or the 'stress' hormones, cortisol and total catecholamines-although meditators tended to have higher mean catecholamine levels. Plasma free fatty acids were significantly elevated in meditators 40 min after completing the period of TM. No clear evidence was thus obtained that any of the stress, or stress-related, hormones were suppressed during or after meditation in the particular setting examined. PMID:3895206

  2. Innovations in classical hormonal targets for endometriosis.

    PubMed

    Pluchino, Nicola; Freschi, Letizia; Wenger, Jean-Marie; Streuli, Isabelle

    2016-01-01

    Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to hormonal imbalance, including estrogen synthesis, metabolism and responsiveness and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed. Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.

  3. Sex hormones and the elderly male voice.

    PubMed

    Gugatschka, Markus; Kiesler, Karl; Obermayer-Pietsch, Barbara; Schoekler, Bernadette; Schmid, Christoph; Groselj-Strele, Andrea; Friedrich, Gerhard

    2010-05-01

    The objective was to describe influences of sex hormones on the male voice in an elderly cohort. Sixty-three elderly males were recruited to undergo assessment of voice parameters, stroboscopy, voice-related questionnaires, a blood draw, and an ultrasound examination of the laryngeal skeleton. The group was divided into men with normal hormonal status and men with lowered levels of sex hormones, called hypogonades. Depending on the level of androgens, voice parameters did not differ. In subjects with decreased levels of estrogens, a significant increase in mean fundamental frequency, as well as changes of highest and lowest frequency plus a shift of the frequency range could be detected. We could detect significant changes of voice parameters depending on status of estrogens in elderly males. Androgens appear to have no impact on the elderly male voice. To our knowledge, this is the first prospective study that correlates sex hormones with voice parameters in elderly men.

  4. Hormone signaling pathways under stress combinations.

    PubMed

    Suzuki, Nobuhiro

    2016-11-01

    As sessile organisms, plants are continuously exposed to various environmental stresses. In contrast to the controlled conditions employed in many researches, more than one or more abiotic and/or biotic stresses simultaneously occur and highly impact growth of plants and crops in the field environments. Therefore, an urgent need to generate crops with enhanced tolerance to stress combinations exists. Researchers, however, focused on the mechanisms underlying acclimation of plants to combined stresses only in recent studies. Plant hormones might be a key regulator of the tailored responses of plants to different stress combinations. Co-ordination between different hormone signaling, or hormone signaling and other pathways such as ROS regulatory mechanisms could be flexible, being altered by timing and types of stresses, and could be different depending on plant species under the stress combinations. In this review, update on recent studies focusing on complex-mode of hormone signaling under stress combinations will be provided.

  5. Genetics Home Reference: combined pituitary hormone deficiency

    MedlinePlus

    ... People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and ...

  6. Aging-Related Hormone Changes in Men

    MedlinePlus

    Healthy Lifestyle Men's health Aging-related hormone changes in men — sometimes called male menopause — are different from those ... to erectile dysfunction and other sexual issues. Make healthy lifestyle choices. Eat a healthy diet and include physical ...

  7. [Dehydroepiandrosterone [DHEA(S)]: anabolic hormone?].

    PubMed

    Luci, Michele; Valenti, Giorgio; Maggio, Marcello

    2010-09-01

    The role of dehydroepiandrosterone (DHEA) and its sulphated form (DHEAS) as anabolic hormones is still debated in the literature. In this review we describe the fundamental steps of DHEA physiological secretion and its peripheral metabolism. Moreover we will list all the observational and intervention studies conducted in humans. Many observational studies have tested the relationship between low DHEA levels and age-related changes in skeletal muscle and bone, while intervention studies underline the positive and significant effects of DHEA treatment on several parameters of body composition. Surprisingly, observational studies are not consistent with different effects in men and women. There is recent evidence of a significant role of DHEA in frailty syndrome and as predictor of mortality. However a more complete approach of the problem suggests the opportunity to not focus only on one single hormonal derangement but to analyze the parallel dysregulation of anabolic hormones including sex steroids, GH-IGF-1 system and other catabolic hormones.

  8. Thyroid hormone, brain development, and the environment.

    PubMed Central

    Zoeller, Thomas R; Dowling, Amy L S; Herzig, Carolyn T A; Iannacone, Eric A; Gauger, Kelly J; Bansal, Ruby

    2002-01-01

    Thyroid hormone is essential for normal brain development. Therefore, it is a genuine concern that thyroid function can be altered by a very large number of chemicals routinely found in the environment and in samples of human and wildlife tissues. These chemicals range from natural to manufactured compounds. They can produce thyroid dysfunction when they are absent from the diet, as in the case of iodine, or when they are present in the diet, as in the case of thionamides. Recent clinical evidence strongly suggests that brain development is much more sensitive to thyroid hormone excess or deficit than previously believed. In addition, recent experimental research provides new insight into the developmental processes affected by thyroid hormone. Based on the authors' research focusing on the ability of polychlorinated biphenyls to alter the expression of thyroid hormone-responsive genes in the developing brain, this review provides background information supporting a new way of approaching risk analysis of thyroid disruptors. PMID:12060829

  9. Amative orientation: the hormonal hypothesis examined.

    PubMed

    Money, John

    2002-01-01

    The hypothesis that human male and female amative orientation, arousal and courtship are sex-hormone dependent had as its precursor John Hunter's recorded but unpublished 18th century experiments of cross-sexed gonadal transplants in chicks. The hypothesis gained momentum in the 20th century after the discovery and eventual marketing of the sex hormones, and after the experimental demonstration by William C. Young that, in guinea-pigs, cross-sexed hormone administered prenatally influenced their subsequent male/female courtship and mating behavior. Comparatively and in review, human clinical syndromes of hypermasculinization and hypomasculinization do not disconfirm the hormonal hypothesis, but they do not adequately confirm it, either. They are compatible with the idea of a cofactor that governs whether amative orientation in practice, ideation and imagery is homosexual, heterosexual or bisexual.

  10. Marihuana smoking suppresses luteinizing hormone in women.

    PubMed

    Mendelson, J H; Mello, N K; Ellingboe, J; Skupny, A S; Lex, B W; Griffin, M

    1986-06-01

    Smoking a single 1-g marihuana cigarette containing 1.8% delta 9-tetrahydrocannabinol induced a 30% suppression of plasma luteinizing hormone levels (P less than .02) in women during the luteal phase of the menstrual cycle. After marihuana placebo cigarette smoking, no luteinizing hormone suppression was observed in the same women under double-blind conditions. Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition.

  11. Climacteric in untreated isolated growth hormone deficiency

    PubMed Central

    Menezes, Menilson; Salvatori, Roberto; Oliveira, Carla R.P.; Pereira, Rossana M.C.; Souza, Anita H.O.; Nobrega, Luciana M.A.; Cruz, Edla do A.C.; Menezes, Marcos; Alves, Érica O.; Aguiar-Oliveira, Manuel H.

    2008-01-01

    Objective To study the time, intensity of symptoms, hormonal profile, and related morbidity of climacteric in women with untreated isolated growth hormone (GH) deficiency (IGHD). Design Women belonging to a large Brazilian kindred with IGHD due to a homozygous mutation in the GH-releasing hormone receptor gene were studied. None of them had ever received GH replacement therapy. A two-step protocol was performed. In the first case-control experiment, aimed to determine the age at climacteric, we compared eight women with IGHD and 32 normal women between 37 and 55 years of age. In the second cross-sectional experiment, aimed to determine the severity of climacteric symptoms, seven women with IGHD (aged 47-65 y) were compared with 13 controls (aged 44-65 y). The Kupperman Index scores, serum follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol levels were determined, and pelvic and mammary ultrasonography, mammography, and colpocytology were performed. Results The number of women with follicle-stimulating hormone above 20 mIU/mL was higher in women with IGHD than controls. Kupperman’s Index was not different between the two groups. Menarche had been delayed and parity was lower in women with IGHD. Hormonal profile was similar, but prolactin was lower in women with IGHD. Uterine volume was smaller in women with IGHD, and endometrial thickness and ovarian volume were similar in the two groups. No difference in breast images or in colpocytology was observed between the two groups. Conclusions Menarche was delayed and the beginning of climacteric is anticipated in untreated lifetime IGHD, but menopausal symptoms and hormonal profile resemble the normal climacteric. PMID:18223507

  12. Young addicted men hormone profile detection

    NASA Astrophysics Data System (ADS)

    Zieliński, Paweł; Wasiewicz, Piotr; Leszczyńska, Bożena; Gromadzka-Ostrowska, Joanna

    2010-09-01

    Hormone parameters were determined in the serum of young addicted men in order to compare them with those obtained from the group of healthy subjects. Three groups were investigated which were named opiates, mixed and control group. Statistical and data mining methods were applied to obtain significant differences. R package was used for all computation. The determination of hormones parameters provide important information relative to impact of addiction.

  13. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2003-08-01

    NFl is characterized by benign Schwann cell tumors called neurofibromas; complex forms can become malignant ( MPNST ). Little is known about...neurofibroma (and/or MPNST ) Schwann cells have increased growth or decreased apoptosis related to steroid hormones. Specific Aim 1 is examining steroid...hormone receptor expression in human normal, NFl neurofibroma and MPNST Schwann cells. Real-time PCR shows very low levels of these receptor

  14. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2004-08-01

    This work is testing the hypothesis that human NF1 neurofibroma (and/or MPNST ) Schwann cells have increased growth or decreased apoptosis in response...to estrogen and progesterone. Specific Aim 1 measured steroid hormone receptor expression in human normal, NF1 neurofibroma and MPNST Schwann cells...responses of the neurofibroma/ MPNST Schwann cell cultures to hormones or antagonists, but no global patterns, indicating tumors behave individually as

  15. Sexual Functioning During Menopause: Schemas, Hormones, and Race

    DTIC Science & Technology

    2010-10-08

    Follicle Stimulating Hormone FSH Hormone Replacement Therapies HRT Human Performance Laboratory HPL Hypoactive Sexual Desire Disorder HSDD...in reproductive status based on changes in reproductive hormones including estradiol (i.e., estrogen), progesterone, follicle stimulating hormone...Self-Schemas & Menopause 79 (i.e., complications). Blood samples of 20mL from each participant were collected in two test tubes containing a

  16. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  17. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  18. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  19. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  20. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  1. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  2. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  3. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  4. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  5. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  6. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  7. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  8. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  9. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  10. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  11. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  12. Stress Hormones and their Regulation in a Captive Dolphin Population

    DTIC Science & Technology

    2013-09-30

    stimulation experiments, an animal’s hormonal and physiological response to a simulated stressor can be evaluated. Adrenocorticotropic hormone (ACTH) is...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Stress Hormones and Their Regulation in a Captive...will determine baseline levels of putative stress hormones and evaluate the functional consequences of increased stress in the bottlenose dolphin

  13. Hormonal Perturbations in Occupationally Exposed Nickel Workers

    PubMed Central

    Beshir, Safia; Ibrahim, Khadiga Salah; Shaheen, Weam; Shahy, Eman M.

    2016-01-01

    BACKGROUND: Nickel exposure is recognized as an endocrine disruptor because of its adverse effects on reproduction. AIM: This study was designed to investigate the possible testiculo-hormonal perturbations on workers occupationally exposed to nickel and to assess its effects on human male sexual function. METHODS: Cross-sectional comparative study, comprising 105 electroplating male non-smoker, non-alcoholic workers exposed to soluble nickel and 60 controls was done. Serum luteinizing hormone, follicle stimulating hormone, testosterone levels and urinary nickel concentrations were determined for the studied groups. RESULTS: Serum luteinizing hormone, follicle stimulating hormone, urinary nickel and the simultaneous incidence of more than one sexual disorder were significantly higher in the exposed workers compared to controls. The occurrence of various types of sexual disorders (decreased libido, impotence and premature ejaculation) in the exposed workers was 9.5, 5.1 and 4.4 folds respectively than the controls. CONCLUSIONS: Exposure to nickel produces possible testiculo-hormonal perturbations in those exposed workers. PMID:27335607

  14. Relation between sex hormones and hepatocellular carcinoma.

    PubMed

    El Mahdy Korah, T; Abd Elfatah Badr, E; Mohamed Emara, M; Ahmed Samy Kohla, M; Gamal Saad Michael, G

    2016-11-01

    Males have higher incidence of hepatocellular carcinoma (HCC) than females. Sex hormones may be a risk factor. The aim was to determine the levels of sex hormones in male and female patients with HCC and cirrhosis versus controls and its possible relationship with HCC. This study was conducted on 90 subjects divided into 40 patients with HCC, 30 patients with liver cirrhosis and 20 apparently healthy subjects complete blood picture, liver function tests. Determination of AFP levels and hormonal assay of oestrogen, progesterone, total testosterone, prolactin, FSH and LH were performed on all subjects. Total testosterone levels were significantly decreased in the two patients groups compared with controls. While oestrogen levels were significantly decreased in the HCC group in comparison with other two groups, prolactin levels were significantly decreased in the HCC group compared with the liver cirrhosis group and increased in the liver cirrhosis group when compared to controls. FSH and LH levels were significantly increased in the HCC group when compared to controls. There is no significant correlation between sex hormones assay and both the size of HCC and degree of cirrhosis in both patient groups. It is concluded that there is no strong relation between sex hormones and HCC when the study was carried out on the levels of sex hormones in patients with HCC.

  15. Weight control, endocrine hormones and cancer prevention.

    PubMed

    King, Brenee; Jiang, Yu; Su, Xiaoyu; Xu, Jianteng; Xie, Linglin; Standard, Joseph; Wang, Weiqun

    2013-05-01

    The prevalence of obesity is increasing which becomes worrisome due to its association with several diseases and certain types of cancers. While weight control through dietary caloric restriction and/or physical activity protects against cancer in animal models, the underlying mechanisms are not fully defined. Weight loss due to negative energy balance is associated with alterations of multiple growth factors and endocrine hormones. The altered hormones and hormone-related functions appear to be responsible for anti-cancer mechanisms. In this review, we summarize the recent studies related to weight loss and the altered endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of adiponectin and glucocorticoids. The potential molecular targets of these hormone-dependent signalling pathways are also discussed. Considering the increasing trends of obesity throughout the world, a better understanding of the underlying mechanisms between body weight, endocrine hormones and cancer risk may lead to novel approaches to cancer prevention and treatment.

  16. Hormone-independent pathways of sexual differentiation.

    PubMed

    Renfree, Marilyn B; Chew, Keng Yih; Shaw, Geoffrey

    2014-01-01

    New observations over the last 25 years of hormone-independent sexual dimorphisms have gradually and unequivocally overturned the dogma, arising from Jost's elegant experiments in the mid-1900s, that all somatic sex dimorphisms in vertebrates arise from the action of gonadal hormones. Although we know that Sry, a Y-linked gene, is the primary gonadal sex determinant in mammals, more recent analysis in marsupials, mice, and finches has highlighted numerous sexual dimorphisms that are evident well before the differentiation of the testis and which cannot be explained by a sexually dimorphic hormonal environment. In marsupials, scrotal bulges and mammary primordia are visible before the testis has differentiated due to the expression of a gene(s) on the X chromosome. ZZ and ZW gynandromorph finches have brains that develop in a sexually dimorphic way dependent on their sex chromosome content. In genetically manipulated mice, it is the X chromosomes, not the gonads, that determine many characters including rate of early development, adiposity, and neural circuits. Even spotted hyenas have sexual dimorphisms that cannot be simply explained by hormonal exposure. This review discusses the recent findings that confirm that there are hormone-independent sexual dimorphisms well before the gonads begin to produce their hormones.

  17. Thyroid hormone, neural tissue and mood modulation.

    PubMed

    Bauer, M; Whybrow, P C

    2001-04-01

    The successful treatment of affective disorders with thyroid hormone exemplifies the suggested inter-relationship between endocrine and neuronal systems in these disorders. Thyroid hormones have a profound influence on behaviour and appear to be capable of modulating the phenotypic expression of major affective illness. Specifically, there is good evidence that triiodothyronine (T3) may accelerate the antidepressant response to tricylic antidepressants, and some studies suggest that T3 may augment the therapeutic response to antidepressants in refractory depressed patients. Open studies have also indicated that adjunctive supraphysiological doses of thyroxine (T4) can ameliorate depressive symptomatology and help stabilize the long-term course of illness in bipolar and unipolar patients, especially women refractory to standard medications. Despite acceptance of the essential role of thyroid hormone on brain maturation and differentiation, and the clinical and therapeutic observations in association with mood disorders, the molecular action that may underlie the mood-modulating properties of thyroid hormone in the adult brain has only recently become the focus of research. The identification of nuclear T3 receptors, the region-specific expression of deiodinase isoenzymes and the molecular analyses of thyroid-responsive genes in the adult brain have provided the biological bases for a better understanding of thyroid hormone action in mature neurons. Also the influence of thyroid hormones on the putative neurotransmitter systems that regulate mood and behaviour, serotonin and norepinephrine, may be helpful in explaining their mood-modulating effects.

  18. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    PubMed

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  19. Hormonal and systemic regulation of sclerostin.

    PubMed

    Drake, Matthew T; Khosla, Sundeep

    2017-03-01

    The Wnt/β-catenin signaling pathway plays an essential role in osteoblast biology. Sclerostin is a soluble antagonist of Wnt/β-catenin signaling secreted primarily by osteocytes. Current evidence indicates that sclerostin likely functions as a local/paracrine regulator of bone metabolism rather than as an endocrine hormone. Nonetheless, circulating sclerostin levels in humans often reflect changes in the bone microenvironment, although there may be exceptions to this observation. Using existing assays, circulating sclerostin levels have been shown to be altered in response to both hormonal stimuli and across a variety of normal physiological and pathophysiological conditions. In both rodents and humans, parathyroid hormone provided either intermittently or continuously suppresses sclerostin levels. Likewise, most evidence from both human and animal studies supports a suppressive effect of estrogen on sclerostin levels. Efforts to examine non-hormonal/systemic regulation of sclerostin have in general shown less consistent findings or have provided associations rather than direct interventional information, with the exception of mechanosensory studies which have consistently demonstrated increased sclerostin levels with skeletal unloading, and conversely decreases in sclerostin with enhanced skeletal loading. Herein, we will review the existent literature on both hormonal and non-hormonal/systemic factors which have been studied for their impact on sclerostin regulation.

  20. Perspectives in hormone replacement therapy.

    PubMed

    Kenemans, P; van Unnik, G A; Mijatovic, V; van der Mooren, M J

    2001-06-15

    Estrogens have been convincingly shown to be highly effective in preventing and reversing menopause-related conditions, such as hot flushes, urogenital complaints, and postmenopausal bone loss. Observational studies report that long-term, estrogen-containing, postmenopausal hormone replacement therapy (HRT) leads to a substantial reduction in hip fractures, myocardial infarction, and possibly colonic cancer, with important consequences for health and quality of life. Estrogen replacement may postpone the onset of Alzheimer's disease and extend life. While many of these effects are biologically plausible, with a variety of cellular mechanisms being involved, only ongoing and future large-scale randomized clinical trials can and should define the effects of HRT more precisely. Long-term compliance is a key issue for long-term benefits, and offering women a choice of administration routes and regimens can only be beneficial in this respect. Pills, patches, gels, and implants are all widely prescribed. Intravaginal or intranasal forms of administration, which are very easy to use and adaptable on an individual level, are among the new options which could improve long-term continuation of HRT use. Fear of breast cancer and recurrence of vaginal bleeding are real concerns for many women considering HRT. This has led to research into lower-dose, estrogen-containing regimens, into continuous combined regimens, and into the potential of estrogen receptor alpha or beta binding molecules that may help to prevent such problems from arising. The prospects for safe and effective postmenopausal HRT with either estrogens or estrogen-like drugs are very promising when these drugs are used in a patient-tailored, risk profile-based manner.

  1. Sexual hormones in human skin.

    PubMed

    Zouboulis, C C; Chen, W-C; Thornton, M J; Qin, K; Rosenfield, R

    2007-02-01

    The skin locally synthesizes significant amounts of sexual hormones with intracrine or paracrine actions. The local level of each sexual steroid depends upon the expression of each of the androgen- and estrogen-synthesizing enzymes in each cell type, with sebaceous glands and sweat glands being the major contributors. Sebocytes express very little of the key enzyme, cytochrome P450c17, necessary for synthesis of the androgenic prohormones dehydroepiandrosterone and androstenedione, however, these prohormones can be converted by sebocytes and sweat glands, and probably also by dermal papilla cells, into more potent androgens like testosterone and dihydrotestosterone. Five major enzymes are involved in the activation and deactivation of androgens in skin. Androgens affect several functions of human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing. Their effects are mediated by binding to the nuclear androgen receptor. Changes of isoenzyme and/or androgen receptor levels may have important implications in the development of hyperandrogenism and the associated skin diseases such as acne, seborrhoea, hirsutism and androgenetic alopecia. On the other hand, estrogens have been implicated in skin aging, pigmentation, hair growth, sebum production and skin cancer. Estrogens exert their actions through intracellular receptors or via cell surface receptors, which activate specific second messenger signaling pathways. Recent studies suggest specific site-related distribution of ERalpha and ERbeta in human skin. In contrast, progestins play no role in the pathogenesis of skin disorders. However, they play a major role in the treatment of hirsutism and acne vulgaris, where they are prescribed as components of estrogen-progestin combination pills and as anti-androgens. These combinations enhance gonadotropin suppression of ovarian androgen production. Estrogen-progestin treatment can reduce the need for shaving

  2. Biological evaluation of (177)Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting.

    PubMed

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

    2015-02-01

    Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with (177)Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10(6) cells. The radio-peptide slowly internalized, and 24.4±0.5% of the total binding was internalized in 4hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02±9.36 at 1.5hr p.i., and was increased to 216.33±61.58 at 24hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this (177)Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors.

  3. In vitro and in vivo evaluation of Alexa Fluor 680-bombesin[7-14]NH2 peptide conjugate, a high-affinity fluorescent probe with high selectivity for the gastrin-releasing peptide receptor.

    PubMed

    Ma, Lixin; Yu, Ping; Veerendra, Bhadrasetty; Rold, Tammy L; Retzloff, Lauren; Prasanphanich, Adam; Sieckman, Gary; Hoffman, Timothy J; Volkert, Wynn A; Smith, Charles J

    2007-01-01

    Gastrin-releasing peptide (GRP) receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN), a 14-amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H(2)N-glycylglycylglycine-BBN[7-14]NH(2) peptide with the following general sequence: H(2)N-G-G-G-Q-W-A-V-G-H-L-M-(NH(2)). This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H(2)N-G-G-G-BBN[7-14]NH(2) in dimethylformamide (DMF). In vitro competitive binding assays, using (125)I-Tyr(4)-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 +/- 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

  4. Identification of the sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and Asian house musk shrew (Suncus murinus).

    PubMed

    Tamura, Kei; Kobayashi, Yasuhisa; Hirooka, Asuka; Takanami, Keiko; Oti, Takumi; Jogahara, Takamichi; Oda, Sen-Ichi; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2016-11-02

    Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. This article is protected by copyright. All rights reserved.

  5. Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

    EPA Science Inventory

    Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

  6. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  7. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    PubMed

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  8. Negative regulation of parathyroid hormone-related protein expression by steroid hormones.

    PubMed

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-04-15

    Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  9. Hormonal Treatment of Metastases of Renal Carcinoma

    PubMed Central

    van der Werf-Messing, B.; van Gilse, H. A.

    1971-01-01

    A series of 33 patients with metastatic renal cancer and evidence of progression of the disease—apart from pulmonary metastases—was treated with hormones (progestogens in 31 cases, androgens in 2 cases) at the Rotterdamsch Radio-Therapeutisch Instituut. Complete or partial spontaneous regression (or non-progression of pulmonary metastases) before hormone treatment was observed in 8 patients (24%). A favourable subjective response to hormone treatment was obtained in 12 patients (36%), while a positive objective response was obtained in 2 (or 3) cases (6-9%). A favourable response was obtained slightly more frequently in men than in women. The hormonal effect was not demonstrably related to any of the following factors: age of the patient, type of progestogen used, the behaviour of concomitant pulmonary metastases, or the presence or absence of the primary growth. The prognosis was unaffected by hormone therapy, but the 2 year survival rate was significantly higher in patients that showed signs of spontaneous regression of pulmonary metastases, as compared with those without these signs. ImagesFig. 1 PMID:5144516

  10. Hormonal treatment of metastases of renal carcinoma.

    PubMed

    van der Werf-Messing, B; van Gilse, H A

    1971-09-01

    A series of 33 patients with metastatic renal cancer and evidence of progression of the disease-apart from pulmonary metastases-was treated with hormones (progestogens in 31 cases, androgens in 2 cases) at the Rotterdamsch Radio-Therapeutisch Instituut. Complete or partial spontaneous regression (or non-progression of pulmonary metastases) before hormone treatment was observed in 8 patients (24%). A favourable subjective response to hormone treatment was obtained in 12 patients (36%), while a positive objective response was obtained in 2 (or 3) cases (6-9%).A favourable response was obtained slightly more frequently in men than in women. The hormonal effect was not demonstrably related to any of the following factors: age of the patient, type of progestogen used, the behaviour of concomitant pulmonary metastases, or the presence or absence of the primary growth.The prognosis was unaffected by hormone therapy, but the 2 year survival rate was significantly higher in patients that showed signs of spontaneous regression of pulmonary metastases, as compared with those without these signs.

  11. Hypothalamic effects of thyroid hormones on metabolism.

    PubMed

    Martínez-Sánchez, Noelia; Alvarez, Clara V; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos; López, Miguel

    2014-10-01

    Over the past few decades, obesity and its related metabolic disorders have increased at an epidemic rate in the developed and developing world. New signals and factors involved in the modulation of energy balance and metabolism are continuously being discovered, providing potential novel drug targets for the treatment of metabolic disease. A parallel strategy is to better understand how hormonal signals, with an already established role in energy metabolism, work, and how manipulation of the pathways involved may lead to amelioration of metabolic dysfunction. The thyroid hormones belong to the latter category, with dysregulation of the thyroid axis leading to marked alterations in energy balance. The potential of thyroid hormones in the treatment of obesity has been known for decades, but their therapeutic use has been hampered because of side-effects. Data gleaned over the past few years, however, have uncovered new features at the mechanisms of action involved in thyroid hormones. Sophisticated neurobiological approaches have allowed the identification of specific energy sensors, such as AMP-activated protein kinase and mechanistic target of rapamycin, acting in specific groups of hypothalamic neurons, mediating many of the effects of thyroid hormones on food intake, energy expenditure, glucose, lipid metabolism, and cardiovascular function. More extensive knowledge about these molecular mechanisms will be of great relevance for the treatment of obesity and metabolic syndrome.

  12. Hormonal control of sulfate uptake and assimilation.

    PubMed

    Koprivova, Anna; Kopriva, Stanislav

    2016-08-01

    Plant hormones have a plethora of functions in control of plant development, stress response, and primary metabolism, including nutrient homeostasis. In the plant nutrition, the interplay of hormones with responses to nitrate and phosphate deficiency is well described, but relatively little is known about the interaction between phytohormones and regulation of sulfur metabolism. As for other nutrients, sulfate deficiency results in modulation of root architecture, where hormones are expected to play an important role. Accordingly, sulfate deficiency induces genes involved in metabolism of tryptophane and auxin. Also jasmonate biosynthesis is induced, pointing to the need of increase the defense capabilities of the plants when sulfur is limiting. However, hormones affect also sulfate uptake and assimilation. The pathway is coordinately induced by jasmonate and the key enzyme, adenosine 5'-phosphosulfate reductase, is additionally regulated by ethylene, abscisic acid, nitric oxid, and other phytohormones. Perhaps the most intriguing link between hormones and sulfate assimilation is the fact that the main regulator of the response to sulfate starvation, SULFATE LIMITATION1 (SLIM1) belongs to the family of ethylene related transcription factors. We will review the current knowledge of interplay between phytohormones and control of sulfur metabolism and discuss the main open questions.

  13. Metabolic hormones in saliva: origins and functions

    PubMed Central

    Zolotukhin, S.

    2012-01-01

    The salivary proteome consists of thousands of proteins, which include, among others, hormonal modulators of energy intake and output. Although the functions of this prominent category of hormones in whole body energy metabolism are well characterized, their functions in the oral cavity, whether as a salivary component, or when expressed in taste cells, are less studied and poorly understood. The respective receptors for the majority of salivary metabolic hormones have been also shown to be expressed in salivary glands, taste cells, or other cells in the oral mucosa. This review provides a comprehensive account of the gastrointestinal hormones, adipokines, and neuropeptides identified in saliva, salivary glands, or lingual epithelium, as well as their respective cognate receptors expressed in the oral cavity. Surprisingly, few functions are assigned to salivary metabolic hormones, and these functions are mostly associated with the modulation of taste perception. Because of the well-characterized correlation between impaired oral nutrient sensing and increased energy intake and body mass index, a conceptually provocative point of view is introduced, whereupon it is argued that targeted changes in the composition of saliva could affect whole body metabolism in response to the activation of cognate receptors expressed locally in the oral mucosa. PMID:22994880

  14. How to use and interpret hormone ratios.

    PubMed

    Sollberger, Silja; Ehlert, Ulrike

    2016-01-01

    Hormone ratios have become increasingly popular throughout the neuroendocrine literature since they offer a straightforward way to simultaneously analyze the effects of two interdependent hormones. However, the analysis of ratios is associated with statistical and interpretational concerns which have not been sufficiently considered in the context of endocrine research. The aim of this article, therefore, is to demonstrate and discuss these issues, and to suggest suitable ways to address them. In a first step, we use exemplary testosterone and cortisol data to illustrate that one major concern of ratios lies in their distribution and inherent asymmetry. As a consequence, results of parametric statistical analyses are affected by the ultimately arbitrary decision of which way around the ratio is computed (i.e., A/B or B/A). We suggest the use of non-parametric methods as well as the log-transformation of hormone ratios as appropriate methods to deal with these statistical problems. However, in a second step, we also discuss the complicated interpretation of ratios, and propose moderation analysis as an alternative and oftentimes more insightful approach to ratio analysis. In conclusion, we suggest that researchers carefully consider which statistical approach is best suited to investigate reciprocal hormone effects. With regard to the hormone ratio method, further research is needed to specify what exactly this index reflects on the biological level and in which cases it is a meaningful variable to analyze.

  15. Role of hormones and neurosteroids in epileptogenesis

    PubMed Central

    Reddy, Doodipala Samba

    2013-01-01

    This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis. PMID:23914154

  16. [Hormonal treatments for fertility disorders in cattle].

    PubMed

    Gundling, N; Feldmann, M; Hoedemaker, M

    2012-01-01

    In dairy cows, hormonal treatments are commonly implemented for acyclicity, silent heat and endometritis. Before treatment, causes of infertility need to be detected and severe failures in housing, feeding or other diseases must be eliminated. Without sustainable improvement of herd management, the use of intensive hormonal treatments will not improve reproductive performance. The most common cause of anoestrous is silent heat. In cows with a palpable corpus luteum, injection of prostaglandin F2α (PGF) reliably induces oestrous. A satisfactory treatment for acyclicity (ovarian dystrophy, ovarian cysts) does not exist. Combinations of different hormones have greater treatment success than a single use of gonadotrophin releasing hormone (GnRH) or human chorionic gonadotrophin (hCG). Strategic use of PGF during the early postpartum period cannot be recommended because positive effects on uterus involution and resumption of the oestrous cycle after calving have not been verified. In contrast, application of GnRH combined with PGF in the puerperal phase appeared to have positive effects on fertility of cows with endometritis. The same applies to PGF for cows with chronic endometritis. Cases of endometritis with fetid odour of vaginal mucus or isolation of Trueperella pyogenes should be treated with antibiotics. Treatment before the 27th day post partum is not advisable. In conclusion, hormonal treatments can be used to treat fertility disorders. Nevertheless, in order to enhance the reproductive performance at the herd level, a sustainable improvement of the general conditions (housing, feeding, animal health, management) is a prerequisite.

  17. Sex hormones in women with kidney disease.

    PubMed

    Ahmed, Sofia B; Ramesh, Sharanya

    2016-11-01

    Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question.

  18. Drug interactions between hormonal contraceptives and antiretrovirals

    PubMed Central

    Nanda, Kavita; Stuart, Gretchen S.; Robinson, Jennifer; Gray, Andrew L.; Tepper, Naomi K.; Gaffield, Mary E.

    2017-01-01

    Objective: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Design: Systematic review of the published literature. Methods: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Results: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Conclusion: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices. PMID:28060009

  19. Actions of Thyroid Hormone Analogues on Chemokines

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  20. The common molecular players in plant hormone crosstalk and signaling.

    PubMed

    Ohri, Puja; Bhardwaj, Renu; Bali, Shagun; Kaur, Ravinderjit; Jasrotia, Shivam; Khajuria, Anjali; Parihar, Ripu D

    2015-01-01

    Plant growth and development is under the control of mutual interactions among plant hormones. The five classical categories of plant hormones include auxins, cytokinins, gibberellins, abscisic acid and ethylene. Additionally, newer classes of plant hormones have been recognized like brassinosteroids, jasmonic acid, salicylic acid and polyamines. These hormones play significant roles in regulating the plant growth and development. Various receptors and key signaling components of these hormones have been studied and identified. At genetic level, crosstalk among the various plant hormones is found to be antagonistic or synergistic. In addition, components of signaling pathway of one plant hormone interact with the signaling components of other hormone. Thus, an attempt has been made to review the literature regarding the role of plant hormones in plant physiology and the common molecular players in their signaling and crosstalk.

  1. Thyroid hormone signaling in energy homeostasis and energy metabolism

    PubMed Central

    McAninch, Elizabeth A.; Bianco, Antonio C.

    2014-01-01

    The thyroid hormone plays a significant role in diverse processes related to growth, development, differentiation, and metabolism. Thyroid hormone signaling modulates energy expenditure through both central and peripheral pathways. At the cellular level, the thyroid hormone exerts its effects after concerted mechanisms facilitate binding to the thyroid hormone receptor. In the hypothalamus, signals from a range of metabolic pathways, including appetite, temperature, afferent stimuli via the autonomic nervous system, availability of energy substrates, hormones, and other biologically active molecules, converge to maintain plasma thyroid hormone at the appropriate level to preserve energy homeostasis. At the tissue level, thyroid hormone actions on metabolism are controlled by transmembrane transporters, deiodinases, and thyroid hormone receptors. In the modern environment, humans are susceptible to an energy surplus, which has resulted in an obesity epidemic and thus understanding the contribution of the thyroid hormone to cellular and organism metabolism is increasingly relevant. PMID:24697152

  2. Gravitational effects on plant growth hormone concentration

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.

    1983-01-01

    Dolk's (1936) finding that more growth hormone diffuses from the lower side of a gravity-stimulated plant shoot than from the upper side is presently confirmed by means of both an isotope dilution assay and selected ion monitoring-gas chromatography-mass spectrometry, and it is established that the asymmetrically distributed hormone is indole-3-acetic acid (IAA). This is the first physicochemical demonstration that there is more IAA on the lower sides of a geostimulated plant shoot. It is also found that free IAA primarily occurs in the conductive vascular tissues of the shoot, while IAA esters predominate in the growing cortical cells. A highly sensitive gas chromatographic isotope dilution assay shows that the hormone asymmetry also occurs in the nonvascular tissue.

  3. Steroid hormone sulphation in lead workers.

    PubMed Central

    Apostoli, P; Romeo, L; Peroni, E; Ferioli, A; Ferrari, S; Pasini, F; Aprili, F

    1989-01-01

    The metabolism of steroid hormones has been investigated in 10 workers exposed to lead and in 10 non-exposed subjects to determine whether lead interferes with the first or second phase reactions of steroid hormone biotransformation, or both. In the exposed workers blood lead concentrations (PbB) ranged from 45 to 69 micrograms/100 ml; in the controls PbB was less than 25 micrograms/100 ml. No statistical differences were found for the total amount of the urinary hormone metabolites, but a drop of about 50% was observed for the sulphated portion. It is suggested that lead interferes with the mechanisms of sulphoconjugation through an effect on the cytosol enzymes sulphotransferase and sulphokinase. PMID:2930732

  4. Thyroid hormone and seasonal regulation of reproduction.

    PubMed

    Yoshimura, Takashi

    2013-08-01

    Organisms living outside the tropics use changes in photoperiod to adapt to seasonal changes in the environment. Several models have contributed to an understanding of this mechanism at the molecular and endocrine levels. Subtropical birds are excellent models for the study of these mechanisms because of their rapid and dramatic response to changes in photoperiod. Studies of birds have demonstrated that light is perceived by a deep brain photoreceptor and long day-induced thyrotropin (TSH) from the pars tuberalis (PT) of the pituitary gland causes local thyroid hormone activation within the mediobasal hypothalamus (MBH). The locally generated bioactive thyroid hormone, T₃, regulates seasonal gonadotropin-releasing hormone (GnRH) secretion, and hence gonadotropin secretion. In mammals, the eyes are the only photoreceptor involved in photoperiodic time perception and nocturnal melatonin secretion provides an endocrine signal of photoperiod to the PT to regulate TSH. Here, I review the current understanding of the hypothalamic mechanisms controlling seasonal reproduction in mammals and birds.

  5. Thyroid Hormones, Oxidative Stress, and Inflammation.

    PubMed

    Mancini, Antonio; Di Segni, Chantal; Raimondo, Sebastiano; Olivieri, Giulio; Silvestrini, Andrea; Meucci, Elisabetta; Currò, Diego

    2016-01-01

    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

  6. Strigolactones: a new hormone with a past.

    PubMed

    Tsuchiya, Yuichiro; McCourt, Peter

    2009-10-01

    The recent discovery of an endogenous hormonal activity for strigolactones in shoot branching was surprising since these molecules were thought to mostly play roles as signaling molecules between organisms. Even in the context of plant hormones, strigolactones appear to be different in that their role in plant development is quite restricted. This most probably reflects early days and new hormonal functions will most probably be found for these compounds in the future. In this respect, the exogenous role of strigolactones in parasitic plant seed germination may hint to functions of this compound in seed development. However, showing new roles for strigolactones in the seed or any other aspect of plant development for that matter will require developing assays in model genetic systems such as Arabidopsis and rice where we can take full advantage of the experimental tools that are available.

  7. Thyroid Hormones, Oxidative Stress, and Inflammation

    PubMed Central

    Raimondo, Sebastiano; Olivieri, Giulio; Meucci, Elisabetta; Currò, Diego

    2016-01-01

    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases. PMID:27051079

  8. [Hormonal treatment for menopause and arterial risk].

    PubMed

    Gueyffier, François; Cornu, Catherine

    2005-02-28

    Is hormonal atmosphere before menopause the cause of the lower risk of coronary heart disease in women? Big clinical trials do not validate this hypothesis, however simple and attractive: in 5 primary or secondary prevention trials, estrogens alone or in association with progestatives to near 32000 women after menopause, do not leave hope for a significant reduction of coronary risk, and show in contrast an 30% increase of stroke risk. These results highlight the crucial importance of clinical trials to validate therapeutic models. The remaining hypotheses on the nature of hormonal treatments and the administration route must follow the same validation process. The prescription of hormonal treatment for menopause illustrates the importance of informed decision including individualised estimate of the risk to benefit ratio.

  9. The Gut Hormones in Appetite Regulation

    PubMed Central

    Suzuki, Keisuke; Jayasena, Channa N.; Bloom, Stephen R.

    2011-01-01

    Obesity has received much attention worldwide in association with an increased risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric surgery is the only effective treatment for obesity in which long-term weight loss is achieved in patients. By contrast, pharmacological interventions for obesity are usually followed by weight regain. Although the exact mechanisms of long-term weight loss following bariatric surgery are yet to be fully elucidated, several gut hormones have been implicated. Gut hormones play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system, in order to regulate food intake. Cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin stimulates food intake. Here, we discuss the role of gut hormones in the regulation of food intake and body weight. PMID:21949903

  10. Preventing leaf identity theft with hormones.

    PubMed

    Lumba, Shelley; McCourt, Peter

    2005-10-01

    Genetic analysis of plant development has begun to demonstrate the importance of hormone synthesis and transport in regulating morphogenesis. In the case of leaf development, for example, auxin pooling determines where a primordium will emerge and leads to the activation of transcription factors, which determine leaf identities by modulating abscisic acid (ABA) and gibberellic acid (GA) concentrations. Signal transduction studies suggest that negative regulation of transcription factors through protein turnover is commonly used as a mechanism of hormone action. Together, these findings suggest that auxin might degrade a repressor that allows the activation of genes that modulate ABA/GA ratios in emerging leaves. With our increased understanding of the molecular basis of hormone signaling, it is becoming possible to overlay important regulators onto signaling modules that determine morphological outputs.

  11. Modification of Chromatin Structure by the Thyroid Hormone Receptor.

    PubMed

    Li; Sachs; Shi; Wolffe

    1999-05-01

    Pioneering experiments and recent observations have established the thyroid hormone receptor as a master manipulator of the chromosomal environment in targeting the activation and repression of transcription. Here we review how the thyroid hormone receptor is assembled into chromatin, where in the absence of thyroid hormone the receptor recruits histone deacetylase to silence transcription. On addition of hormone, the receptor undergoes a conformational change that leads to the release of deacetylase, while facilitating the recruitment of transcriptional coactivators that act as histone acetyltransferases. We discuss the biological importance of these observations for gene control by the thyroid hormone receptor and for oncogenic transformation by the mutated thyroid hormone receptor, v-ErbA.

  12. The role of sex hormones on fibromyalgia pain mediators.

    PubMed

    Bramwell, Bethany L

    2010-01-01

    Understanding the role of the sex hormones in the pain mechanisms and various effects on nociceptors is imperative to managing potential underlying hormone disruptions in chronic pain syndromes. The myriad of overlapping symptoms between mid-life hormone imbalances and mid-life onset of fibromyalgia syndrome in women indicates a role for sex hormones in the etiology of fibromyalgia syndrome, which is, as of yet, unsupported by the literature. However, fibromyalgia treatment should be tailored to the individual needs of the patient, and adrenal, thyroid, and ovarian hormone support can lessen the painful burden of fibromyalgia through the modulation of various hormone-regulated pain-production pathways.

  13. Minireview: Nuclear Receptor-Controlled Steroid Hormone Synthesis and Metabolism

    PubMed Central

    He, Jinhan; Cheng, Qiuqiong; Xie, Wen

    2010-01-01

    Steroid hormones are essential in normal physiology whereas disruptions in hormonal homeostasis represent an important etiological factor for many human diseases. Steroid hormones exert most of their functions through the binding and activation of nuclear hormone receptors (NRs or NHRs), a superfamily of DNA-binding and often ligand-dependent transcription factors. In recent years, accumulating evidence has suggested that NRs can also regulate the biosynthesis and metabolism of steroid hormones. This review will focus on the recent progress in our understanding of the regulatory role of NRs in hormonal homeostasis and the implications of this regulation in physiology and diseases. PMID:19762543

  14. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    PubMed

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

  15. Receptors for parathyroid hormone and parathyroid hormone-related peptide: from molecular cloning to definition of diseases.

    PubMed

    Jüppner, H; Schipani, E

    1996-07-01

    The parathyroid hormone/parathyroid hormone-related peptide receptor belongs to a distinct family of G protein-coupled receptors, the members of which usually signal through at least two second messenger systems, adenylate cyclase and phospholipase C. The parathyroid hormone/ parathyroid hormone-related peptide receptor is most abundantly expressed in bone, kidney and growth-plate chondrocytes, and, at lower levels, in a variety of fetal and adult tissues. To search for human diseases that are caused by parathyroid hormone/parathyroid hormone-related peptide receptor defects, genomic DNA of patients with pseudohypoparathyroidism type Ib and of patients with Jansen's metaphyseal chondrodysplasia was screened for mutations in all coding exons of the receptor gene. Inactivating parathyroid hormone/parathyroid hormone-related peptide receptor mutations were excluded in patients with pseudohypoparathyroidism type Ib. However, a receptor mutation that causes agonist-independent, constitutive cAMP accumulation was identified in a patient with Jansen's metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism associated with hypercalcemia despite normal or low concentrations of parathyroid hormone and parathyroid hormone-related peptide. These findings allow the conclusion to be drawn that parathyroid hormone/parathyroid hormone-related peptide receptors mediate the endocrine actions of parathyroid hormone, which are required for the control of calcium homeostasis and the autocrine-paracrine actions of parathyroid hormone-related peptide, which are required for normal growth-plate development.

  16. Plant Biology. Hormones and the green revolution.

    PubMed

    Salamini, Francesco

    2003-10-03

    The success of the green revolution largely resulted from the creation of dwarf cultivars of wheat and rice, which had much higher yields than conventional crops. Characterization of these dwarf cultivars showed that the mutant genes were involved in either the synthesis or signaling of gibberellin, a plant growth hormone. In his Perspective, Salamini highlights new work (Multani et al.) that identifies the cause of dwarfism in agronomically important varieties of maize and sorghum. In these cases, dwarfism is caused by defective transport of another growth hormone called auxin.

  17. How sex hormones promote skeletal muscle regeneration.

    PubMed

    Velders, Martina; Diel, Patrick

    2013-11-01

    Skeletal muscle regeneration efficiency declines with age for both men and women. This decline impacts on functional capabilities in the elderly and limits their ability to engage in regular physical activity and to maintain independence. Aging is associated with a decline in sex hormone production. Therefore, elucidating the effects of sex hormone substitution on skeletal muscle homeostasis and regeneration after injury or disuse is highly relevant for the aging population, where sarcopenia affects more than 30 % of individuals over 60 years of age. While the anabolic effects of androgens are well known, the effects of estrogens on skeletal muscle anabolism have only been uncovered in recent times. Hence, the purpose of this review is to provide a mechanistic insight into the regulation of skeletal muscle regenerative processes by both androgens and estrogens. Animal studies using estrogen receptor (ER) antagonists and receptor subtype selective agonists have revealed that estrogens act through both genomic and non-genomic pathways to reduce leukocyte invasion and increase satellite cell numbers in regenerating skeletal muscle tissue. Although animal studies have been more conclusive than human studies in establishing a role for sex hormones in the attenuation of muscle damage, data from a number of recent well controlled human studies is presented to support the notion that hormonal therapies and exercise induce added positive effects on functional measures and lean tissue mass. Based on the fact that aging human skeletal muscle retains the ability to adapt to exercise with enhanced satellite cell activation, combining sex hormone therapies with exercise may induce additive effects on satellite cell accretion. There is evidence to suggest that there is a 'window of opportunity' after the onset of a hypogonadal state such as menopause, to initiate a hormonal therapy in order to achieve maximal benefits for skeletal muscle health. Novel receptor subtype selective

  18. New active series of growth hormone secretagogues.

    PubMed

    Guerlavais, Vincent; Boeglin, Damien; Mousseaux, Delphine; Oiry, Catherine; Heitz, Annie; Deghenghi, Romano; Locatelli, Vittorio; Torsello, Antonio; Ghé, Corrado; Catapano, Filomena; Muccioli, Giampiero; Galleyrand, Jean-Claude; Fehrentz, Jean-Alain; Martinez, Jean

    2003-03-27

    New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)

  19. Calcitonin-like diuretic hormones in insects.

    PubMed

    Zandawala, Meet

    2012-10-01

    Insect neuropeptides control various biological processes including growth, development, homeostasis and reproduction. The calcitonin-like diuretic hormone (CT/DH) is one such neuropeptide that has been shown to affect salt and water transport by Malpighian tubules of several insects. With an increase in the number of sequenced insect genomes, CT/DHs have been predicted in several insect species, making it easier to characterize the gene encoding this hormone and determine its function in the species in question. This mini review summarizes the current knowledge on insect CT/DHs, focusing on mRNA and peptide structures, distribution patterns, physiological roles, and receptors in insects.

  20. Gut hormone GPCRs: structure, function, drug discovery.

    PubMed

    Cordomí, Arnau; Fourmy, Daniel; Tikhonova, Irina G

    2016-12-01

    Crystallization and determination of the high resolution three-dimensional structure of the β2-adrenergic receptor in 2007 was followed by structure elucidation of a number of other receptors, including those for neurotensin and glucagon. These major advances foster the understanding of structure-activity relationship of these receptors and structure-based rational design of new ligands having more predictable activity. At present, structure determination of gut hormone receptors in complex with their ligands (natural, synthetic) and interacting signalling proteins, for example, G-proteins, arrestins, represents a challenge which promises to revolutionize gut hormone endocrinonology.