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Sample records for neuroendocrine gnrh cells

  1. Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

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    Lyes eDerouiche

    2015-12-01

    Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

  2. The GnRH receptor and the response of gonadotrope cells to GnRH pulse frequency code. A story of an atypical adaptation of cell function relying on a lack of receptor homologous desensitization.

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    Christian Bleux

    2010-01-01

    Full Text Available Brain control of the reproductive system is mediated through hypothalamic gonadotropin-releasing hormone (GnRH which activates specific receptors (GnRHR present at the surface of the pituitary gonadotropes to trigger secretion of the two gonadotropins LH and FSH. A unique feature of this system is the high dependence on the secretion mode of GnRH, which is basically pulsatile but undergoes considerable fluctuations in pulse frequency pattern in response to endogenous or external factors. How the physiological fluctuations of GnRH secretion that orchestrate normal reproduction are decoded by the gonadotrope cell machinery to ultimately control gonadotropin release and/or subunit gene transcription has been the subject of intensive studies during the past decades. Surprisingly, the mammalian GnRHR is unique among G protein-coupled receptor family as it lacks the carboxy-terminal tail usually involved in classical endocytotic process. Accordingly, it does not desensitize properly and internalizes very poorly. Both this atypical intrinsic property and post-receptor events may thus contribute to decode the GnRH signal. This includes the participation of a network of signaling pathways that differently respond to GnRH together with a growing amount of genes differentially sensitive to pulse frequency. Among these are two pairs of genes, the transcription factors EGR-1 and NAB, and the regulatory factors activin and follistatin, that function as intracellular autoregulatory feedback loops controlling respectively LHbeta and FSHbeta gene expression and hence, LH and FSH synthesis. Pituitary gonadotropes thus represent a unique model of cells functionally adapted to respond to a considerably fluctuating neuroendocrine stimulation, from short individual pulses to sustained GnRH as observed at the proestrus of ovarian cycle. Altogether, the data emphasize the adaptative reciprocal complementarity of hypothalamic GnRH neurones and pituitary gonadotropes to

  3. The frequency of neuroendocrine cell hyperplasia in patients with pulmonary neuroendocrine tumours and non-neuroendocrine cell carcinomas.

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    Rizvi, Selim M H; Goodwill, Joseph; Lim, Eric; Yap, Yoong K; Wells, Athol U; Hansell, David M; Davis, Peter; Selim, Abdel-Ghani; Abdel-Ghani, Syed; Goldstraw, Peter; Nicholson, Andrew G

    2009-09-01

    To evaluate the frequency of neuroendocrine cell hyperplasia (NEH) in resected neuroendocrine tumours and non-neuroendocrine cell carcinomas and to study its relationship to selected clinical parameters. Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) (P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) (P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) (P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH. NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential.

  4. [EGFR-expression in pulmonary neuroendocrine cell hyperplasia].

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    Kuhnen, C; Winter, B U

    2006-03-01

    15 cases of pulmonary neuroendocrine cell hyperplasia (carcinoid-tumorlets, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia/DIPNECH) and 20 neuroendocrine pulmonary tumors (10 carcinoid tumors, 5 large cell neuroendocrine, and 5 small cell neuroendocrine lung carcinomas) were immunohistochemically analyzed for the expression of epidermal growth factor receptor (EGFR, = HER-1). All cases of neuroendocrine cell hyperplasia exhibited a maximum EGFR expression (score 3 in 100% of cells) showing predominantly membranous, partly cytoplasmic staining. 4 ot the 10 carcinoid tumors were strongly positive for EGFR, whereas the other 6 were EGFR-negative. A total of 90% of large cell neuroendocrine and small cell neuroendocrine carcinomas were negative for EGFR. Overexpression of EGFR in pulmonary neuroendocrine cell hyperplasia might be significant for the pathogenesis of these lesions. As DIPNECH is characterized by clinical signs and symptoms including mild cough and obstructive functional impairment, a specific antagonistic therapeutic trial could aim at blocking EGFR/HER-1 or its subsequent signal transduction pathway.

  5. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  6. Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases

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    Cevriye Cansız Ersöz

    2016-01-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors.

  7. Receptor-mediated binding and uptake of GnRH agonist and antagonist by pituitary cells

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    Jennes, L.; Stumpf, W.E.; Conn, P.M.

    1984-01-01

    The intracellular pathway of an enzyme resistant GnRH agonist (D- Lys6 -GnRH) conjugated to ferritin or to colloidal gold was followed in cultured pituitary cells. After an initial uniform distribution over the cell surface of gonadotropes, the electrondense marker was internalized, either individually or in small groups. After longer incubation times, the marker appeared in the lysosomal compartment and the Golgi apparatus, where it could be found in the vesicular as well as cisternal portion. In addition, the receptor-mediated endocytosis of the GnRH antagonist D-p-Glu1-D-Phe2-D-Trp3-D- Lys6 -GnRH was studied by light and electron microscopic autoradiography after 30 and 60 min of incubation to ensure uptake. At both time points, in in vitro as well as in vivo studies, silver grains were localized over cytoplasmic organelles of castration cells, including dilated endoplasmic reticulum, lysosomes, and clear vesicles. No consistent association with cell nuclei, mitochondria, or secretory vesicles could be observed. The results suggest that both agonist and antagonist are binding selectively to the plasma membrane of gonadotropes and subsequently are taken up via receptor-mediated endocytosis for degradation or possible action on synthetic processes.

  8. Regulation of GnRH receptors by progesterone and inhibin in ovine pituitary cell culture

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    Laws, S.C.

    1988-01-01

    The effects of progesterone (P{sub 4}) and the gonadal protein, inhibin, on gonadotropin-releasing hormone (GnRH) receptor number and binding affinity were investigated in vitro, using ovine pituitary cells in culture. Changes in GnRH binding were correlated with GnRH-stimulated luteinizing hormone (LH) release following pretreatment with P{sub 4} and inhibin. Ovine pituitary cells in culture were preincubated with P{sub 4} or porcine inhibin (I{sub P}) for 24 or 48 hours (h). Cells were collected and analyzed for GnRH binding using a radioligand-receptor assay. des-Gly{sup 10}-(D-Ala{sup 6})-LHRH-ethyl-amide was used as the radiolabeled GnRh superagonist analog (mono-{sup 125}I-GnRH-A) and as competing ligand. Treatment with P{sub 4} progressively decreased GnRH-A binding capacity by 44.3% and 71.8% of the control following pretreatment for 24 or 48 h, respectively. When P{sub 4} was removed from the cultures, GnRH-A binding capacity partially returned to control levels within 24 h. Decreased GnRH-A binding was closely correlated with the reduction in GnRH-stimulated LH release which was observed following 24 or 48 h pretreatment with P{sub 4}.

  9. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

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    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  10. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

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    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

  11. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

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    Zhang, Xiaomei

    2010-03-04

    We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

  12. GnRH receptors in human granulosa cells: Anatomical localization and characterization by autoradiographic study

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    Latouche, J.; Crumeyrolle-Arias, M.; Jordan, D.; Kopp, N.; Augendre-Ferrante, B.; Cedard, L.; Haour, F. (Institut Pasteur, Paris (France))

    1989-09-01

    The presence of receptors for GnRH in human ovary has been investigated by quantitative autoradiography. Simultaneous visualization and characterization of specific receptors on frozen sections were obtained on six pairs of human ovaries. Among them only one exhibited a large preovulatory follicle. This dominant follicle exhibited a specific and high affinity binding capacity for {sup 125}I-GnRHa exclusively localized on the granulosa cell layer. Analysis of saturation curve indicates a Kd value of 0.22 nM and Bmax of 9.6 fmol/mg protein. In contrast LH-hCG binding sites were present in all antral follicles. These data demonstrate for the first time the presence of high affinity GnRH receptors in human granulosa cells at a late stage of follicular maturation.

  13. Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling.

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    Sabado, Virginie; Barraud, Perrine; Baker, Clare V H; Streit, Andrea

    2012-02-15

    A small population of neuroendocrine cells in the rostral hypothalamus and basal forebrain is the key regulator of vertebrate reproduction. They secrete gonadotropin-releasing hormone (GnRH-1), communicate with many areas of the brain and integrate multiple inputs to control gonad maturation, puberty and sexual behavior. In humans, disruption of the GnRH-1 system leads to hypogonadotropic gonadism and Kallmann syndrome. Unlike other neurons in the central nervous system, GnRH-1 neurons arise in the periphery, however their embryonic origin is controversial, and the molecular mechanisms that control their initial specification are not clear. Here, we provide evidence that in chick GnRH-1 neurons originate in the olfactory placode, where they are specified shortly after olfactory sensory neurons. FGF signaling is required and sufficient to induce GnRH-1 neurons, while retinoic acid represses their formation. Both pathways regulate and antagonize each other and our results suggest that the timing of signaling is critical for normal GnRH-1 neuron formation. While Kallmann's syndrome has generally been attributed to a failure of GnRH-1 neuron migration due to impaired FGF signaling, our findings suggest that in at least some Kallmann patients these neurons may never be specified. In addition, this study highlights the intimate embryonic relationship between GnRH-1 neurons and their targets and modulators in the adult. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Large-cell neuroendocrine carcinoma of the uterine cervix- a ...

    African Journals Online (AJOL)

    Objective. The present study describes 5 cases of large-cell neuroendocrine carcinoma (LCNEC) of the uterine cervix, evaluating their clinical features and pathological profiles. Methods. Clinical data were obtained from the patients' clinical files at the combined gynaecological-oncology unit of Johannesburg Hospital and ...

  15. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

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    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  16. A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

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    Godwin Ofikwu

    2015-01-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linear proliferation. It is usually seen in middle-aged, nonsmoking women with symptoms of cough, dyspnea, and wheezing. We present a 45-year-old, nonsmoking woman who presented with symptoms of DIPNECH associated with bilateral pulmonary nodules and left hilar adenopathy. Of interest, DIPNECH in our patient was associated with metastatic pulmonary carcinoids, papillary carcinoma of the left breast, oncocytoma and angiomyolipoma of her left kidney, and cortical nodules suggestive of tuberous sclerosis. She had video assisted thoracoscopic surgery (VATS, modified radical mastectomy with reconstruction, and radical nephrectomy. She is currently symptom-free most of the time with over two years of follow-up.

  17. Rostro-caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites.

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    Geller, Sarah; Lomet, Didier; Caraty, Alain; Tillet, Yves; Duittoz, Anne; Vaudin, Pascal

    2017-10-03

    During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo. More than 90% of migrating GnRH neurones were found to be associated with glial cells. There was no change in the cellular microenvironment of GnRH neurones in the regions crossed during embryonic development as glial cells formed the main microenvironment of these neurones (53.4%). However, the phenotype of OEC associated with GnRH neurones changed across regions. The OEC progenitors immunoreactive to brain lipid binding protein formed the microenvironment of migrating GnRH neurones from the vomeronasal organ to the telencephalon and were also present in the diencephalon. However, during GnRH neurone migration, maturation of OEC to [GFAP+] state (glial fibrillary acid protein) was only observed in the nasal septum. Inducing depletion of OEC in maturation, using transgenic mice expressing herpes simplex virus thymidine kinase driven by the GFAP promoter, had no impact on neurogenesis or on triggering GnRH neurones migration in nasal explant culture. Nevertheless, depletion of [GFAP+] cells decreased GnRH neurites outgrowth by 57.4%. This study suggests that specific maturation of OEC in the nasal septum plays a role in morphological differentiation of GnRH neurones. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. A minimalist model of calcium-voltage coupling in GnRH cells

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    Rennie, Martin; Chan, Rossanna; Duan Wen; Sneyd, James [Department of Mathematics, University of Auckland, Auckland 1142 (New Zealand); Schneider, David, E-mail: schneide@tandar.cnea.gov.ar [Departamento de Fisica, Comision Nacional de Energia Atomica. Av. del Libertador 8250, 1429 Buenos Aires (Argentina)

    2011-03-01

    We present a minimalist model to describe the interplay between burst firing and calcium dynamics in Gonadotropin-releasing hormone (GnRH) cells. This model attempts to give a qualitative representation of Duan's model [3], and it comprises two FithzHugh-Nagumo (FHN) coupled systems describing the dynamics of the membrane potential and calcium concentration in the GnRH cells. Within the framework of our minimalist model, we find that the calcium subsystem drives burst firing by making the voltage subsystem to undergo a Hopf bifurcation. Specifically, fast relaxation oscillations occur in a specific region of the c-z plane (c being the calcium concentration, and z a calcium-dependent gating variable). Slow calcium oscillations, instead, are carried by the voltage subsystem by successive shifts of the calcium steady state, and have the net effect of an external perturbation. The full comprehension of the phase-plane of the voltage subsystem and the 3-dimensional phase-space of the calcium subsystem ultimately allows us to study the behaviours of the entire model under the change of certain parameters. Those special parameters do not necessarily follow realistic assumptions, but merely intend to mimic some pharmacological tests which have been performed experimentally and also simulated by Duan's model under the corresponding physiological considerations.

  19. Hedgehog-PKA signaling and gnrh3 regulate the development of zebrafish gnrh3 neurons.

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    Ming-Wei Kuo

    Full Text Available GnRH neurons secrete GnRH that controls the development of the reproduction system. Despite many studies, the signals controlling the development of GnRH neurons from its progenitors have not been fully established. To understand the development of GnRH neurons, we examined the development of gnrh3-expressing cells using a transgenic zebrafish line that expresses green fluorescent protein (GFP and LacZ driven by the gnrh3 promoter. GFP and LacZ expression recapitulated that of gnrh3 in the olfactory region, olfactory bulb and telencephalon. Depletion of gnrh3 by morpholinos led to a reduction of GFP- and gnrh3-expressing cells, while over-expression of gnrh3 mRNA increased the number of these cells. This result indicates a positive feed-forward regulation of gnrh3 cells by gnrh3. The gnrh3 cells were absent in embryos that lack Hedgehog signaling, but their numbers were increased in embryos overexpressing shhb. We manipulated the amounts of kinase that antagonizes the Hedgehog signaling pathway, protein kinase A (PKA, by treating embryos with PKA activator forskolin or by injecting mRNAs encoding its constitutively active catalytic subunit (PKA* and dominant negative regulatory subunit (PKI into zebrafish embryos. PKA* misexpression or forskolin treatment decreased GFP cell numbers, while PKI misexpression led to ectopic production of GFP cells. Our data indicate that the Hedgehog-PKA pathway participates in the development of gnrh3-expressing neurons during embryogenesis.

  20. Clonality analysis of neuroendocrine cells in gastric adenocarcinoma

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    Wang, Ling-Ling; Yao, Gen-You; Zhao, Zhong-Sheng; Wei, Xiao-Li; Xu, Ru-Jun

    2013-01-01

    AIM: To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma. METHODS: In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study. Third, genome-wide microsatellite abnormalities [microsatellite instability (MSI), loss of heterozygosity (LOH)] and p53 mutation were detected by polymerase chain reaction (PCR)-single-strand conformation polymer- phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells. RESULTS: The total incidence rate of MSI was 27.4%, while LOH was 17.9%. Ten cases had a highest concordance for the two types of cells. The other samples had similar microsatellite changes, except for cases 7 and 10. Concordant p53 mutations exhibited in sample 4, 14, 21 and 27, and there were different mutations between two kinds of cells in case 7. In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis. In brief, NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30). In the other three cases, different MSI, LOH or p53 mutation occurred. CONCLUSION: NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation. PMID:23983439

  1. Rb Loss is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma

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    Tan, Hsueh-Li; Sood, Akshay; Rahimi, Hameed A.; Wang, Wenle; Gupta, Nilesh; Hicks, Jessica; Mosier, Stacy; Gocke, Christopher D.; Epstein, Jonathan I.; Netto, George J.; Liu, Wennuan; Isaacs, William B.; De Marzo, Angelo M.; Lotan, Tamara L.

    2014-01-01

    Purpose Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide diagnosis and therapy of this aggressive tumor. Experimental Design We examined the status of RB1, TP53 and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy number alteration analysis and sequencing of formalin fixed paraffin-embedded specimens. Results We found Rb protein loss in 90% (26/29) of small cell carcinoma cases with RB1 allelic loss in 85% (11/13) of cases. Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3/7) showed Rb protein loss. In contrast, only 7% (10/150) of primary high grade acinar carcinomas, 11% (4/35) of primary acinar carcinomas with neuroendocrine differentiation, and 15% (2/13) of metastatic castrate resistant acinar carcinomas showed Rb protein loss. Loss of PTEN protein was seen in 63% (17/27) of small cell carcinomas, with 38% (5/13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% (14/25) of small cell carcinomas, with 60% (6/10) of cases showing TP53 mutation. Conclusions Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by validated IHC assay. As Rb protein loss rarely occurs in high grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target. PMID:24323898

  2. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  3. Regulation of luteinizing hormone (LH) subunit biosynthesis in cultured male anterior pituitary cells: effects of GnRH and testosterone

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    Krummen, L.A.

    1988-01-01

    The purpose of this study was to evaluate the direct effects of testosterone (T) on LH subunit apoprotein synthesis, glycosylation and release by the male pituitary. Cells from 1 wk castrate rats were cultured for 48 h in steroid-free medium followed by 48h in media /+-/10nM T. The cells were then incubated for 2, 4, 6, 8, or 12h in media containing (/sup 35/S)-methionine (/sup 35/S-Met) or (/sup 3/H)-glucosamine (/sup 3/H-Gln), /+-/1nM GnRH (exp 1) or in media containing precursors /+-/ 10nM T and/or 1nM GnRH (exp 2). Radiolabeled precursor incorporation into LH subunits was determined by immunoprecipitation followed by SDS-PAGE. In experiment 1, precursor incorporation into total protein (TP) and LH subunits increased linearly with time for at least 8h. GnRH did not effect precursor incorporation in to TP or /sup 35/S-Met labeling of LH subunits, but stimulated a linear, time-dependent accumulation of /sup 3/H-Gln into total LH subunits and the release of RIA-LH and radiolabeled subunits into media. Based on these results, the effects of T on LH subunit biosynthesis were studied during an 8h incubation. In experiment 2, GnRH enhanced the total /sup 3/H-Gln incorporation (but not /sup 35/S-Met incorporation) into both LH subunits. GnRH stimulated the release of /sup 35/S-Met LH..cap alpha.. and /sup 3/H-Gln LH subunits into media and increased the relative glycosylation of secreted LH subunits without altering the relative glycosylation of intracellular LH subunits. T inhibited RIA-LH release and incorporation of both precursors into total and secreted LH subunits (/+-/GnRH). However, only the relative glycosylation of secreted LH..cap alpha.. was reduced by T (/+-/GnRh).

  4. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH in cystic fibrosis epithelial cells.

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    Nathalie Benz

    Full Text Available Cystic fibrosis (CF, the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(- channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5 directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(- channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R and that GnRH induces an AnxA5 overexpression and an increased Cl(- channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  5. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH) in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Benz, Nathalie; Le Hir, Sophie; Norez, Caroline; Kerbiriou, Mathieu; Calvez, Marie-Laure; Becq, Frédéric; Trouvé, Pascal; Férec, Claude

    2014-01-01

    Cystic fibrosis (CF), the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER) and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(-) channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5) directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(-) channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH) increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R) and that GnRH induces an AnxA5 overexpression and an increased Cl(-) channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  6. Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells

    Science.gov (United States)

    Terasaka, Tomohiro; Otsuka, Fumio; Tsukamoto, Naoko; Nakamura, Eri; Inagaki, Kenichi; Toma, Kishio; Ogura-Ochi, Kanako; Glidewell-Kenney, Christine; Lawson, Mark A.; Makino, Hirofumi

    2014-01-01

    Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentrationdependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ERα and ERβ, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells. PMID:23880664

  7. Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study.

    Science.gov (United States)

    Kataria, Hardeep; Gupta, Muskan; Lakhman, Sukhwinder; Kaur, Gurcharan

    2015-10-01

    Ashwagandha (Withania somnifera) has a long history in traditional medicines as an aphrodisiac. It has been known to influence sexual behaviour in animal models but mechanism of action is still unknown. The present study was aimed to investigate the mechanisms by which Ashwagandha extract exert its gonadotropic activities. Due to the complexity of neuroendocrine pathways, there are limited in vitro models available despite the strong demand for such systems to study and predict neuroendocrine effects of chemicals or natural products. Immortalized rat hypothalamic GnV-3 cell line was investigated as a model to screen for neuroendocrine effects of Ashwagandha extract. GnV-3 cells were cultured under different media conditions and evaluated after treatment with Ashwagandha water extract, for GnRH expression and release by immunostaining and ELISA respectively. These cells acquired differentiated morphology, characteristic shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells exhibited upregulation of plasticity related polysialylated neural cell adhesion molecule (PSA-NCAM) and mature dendrite marker microtubule associated protein (MAP2) as well as GnRH expression and release. Chloroform fraction of the extract proved to exhibit all the bioactive properties as it induced differentiation and upregulated GnRH and MAP2 expression in GnV-3 cells, similar to Ashwagandha extract. Withanone and Withaferin A were found to be present in ASH-WEX and chloroform fraction while Withanone came out to be the major constituent of chloroform fraction. The preliminary in vivo studies in adult male animals showed that ASH-WEX was able to upregulate the GnRH levels although non-significantly. Taken together, this data demonstrate significant morphological and physiological changes in GnV-3 cells after treatment with Ashwagandha extract and may suggest the potential beneficial effects of Ashwagandha on reproductive functions in vivo. Copyright © 2015 Elsevier Ltd

  8. Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    2013-06-01

    Full Text Available We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

  9. Genetic and molecular coordinates of neuroendocrine lung tumors, with emphasis on small-cell lung carcinomas

    National Research Council Canada - National Science Library

    Koutsami, Marilena K; Doussis-Anagnostopoulou, Ipatia; Papavassiliou, Athanasios G; Gorgoulis, Vassilis G

    2002-01-01

    .... Current information on established and putative diagnostic and prognostic markers of neuroendocrine tumors are evaluated, with a special reference to small-cell lung carcinoma, due to its higher...

  10. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.

    OpenAIRE

    Bang, Y J; Pirnia, F; Fang, W G; Kang, W K; Sartor, O; Whitesell, L; Ha, M J; Tsokos, M.; Sheahan, M D; Nguyen, P.

    1994-01-01

    Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analog...

  11. Evaluation of neuroendocrine markers in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Kauppila Saila

    2010-05-01

    Full Text Available Abstract Background The purpose of the study was to examine serotonin, CD56, neurone-specific enolase (NSE, chromogranin A and synaptophysin by immunohistochemistry in renal cell carcinomas (RCCs with special emphasis on patient outcome. Methods We studied 152 patients with primary RCCs who underwent surgery for the removal of kidney tumours between 1990 and 1999. The mean follow-up was 90 months. The expression of neuroendocrine (NE markers was determined by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, clinical stage, Fuhrman grade and patient outcome. Results Eight percent of tumours were positive for serotonin, 18% for CD56 and 48% for NSE. Chromogranin A immunostaining was negative and only 1% of the tumours were synaptophysin immunopositive. The NSE immunopositivity was more common in clear cell RCCs than in other subtypes (p = 0.01. The other NE markers did not show any association with the histological subtype. Tumours with an immunopositivity for serotonin had a longer RCC-specific survival and tumours with an immunopositivity for CD56 and NSE had a shorter RCC-specific survival but the difference was not significant. There was no relationship between stage or Fuhrman grade and immunoreactivity for serotonin, CD56 and NSE. Conclusions Serotonin, CD56 and NSE but not synaptophysin and chromogranin A are expressed in RCCs. However, the prognostic potential of these markers remains obscure.

  12. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  13. NOTCH SIGNALLING MODULATES HYPOXIA-INDUCED NEUROENDOCRINE DIFFERENTIATION OF HUMAN PROSTATE CANCER CELLS

    Science.gov (United States)

    Danza, Giovanna; Di Serio, Claudia; Rosati, Fabiana; Lonetto, Giuseppe; Sturli, Niccolò; Kacer, Doreen; Pennella, Antonio; Ventimiglia, Giuseppina; Barucci, Riccardo; Piscazzi, Annamaria; Prudovsky, Igor; Landriscina, Matteo; Marchionni, Niccolò; Tarantini, Francesca

    2012-01-01

    Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation has been associated with tumor progression, poor prognosis and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavourable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells, in vitro. Results exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent down regulation of Notch-mediated signalling, as demonstrated by reduced levels of the Notch target genes, Hes1 and Hey1. Neuroendocrine differentiation was promoted by attenuation of Hes1 transcription, as cells expressing a dominant negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia down regulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen independent cell lines, PC3 and Du145, it did not change the extent of NE differentiation in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur. Conclusions hypoxia induces neuroendocrine differentiation of LNCaP cells in vitro, which appears to be driven by the inhibition of Notch signalling with subsequent down-regulation of Hes1 transcription. PMID:22172337

  14. Large cell neuroendocrine carcinoma of the kidney with cardiac metastasis: a case report

    Directory of Open Access Journals (Sweden)

    Moeka Shimbori

    2017-10-01

    Full Text Available Abstract Background Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis. Case presentation A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart. A cardiac biopsy under transesophageal echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple lung lesions were detected, and a right nephrectomy was performed after these metastases were suspected to have originated from renal carcinoma. Large cell neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic metastasis was detected on computed tomography postoperatively. Three courses of chemotherapy with carboplatin and irinotecan were administered, and were temporarily effective against the metastatic lesions in the lungs and pancreas. However, our patient’s general condition deteriorated with the progression of the lesions, and he died 9 months after his initial examination. Conclusions Multi-agent chemotherapy, including platinum-based drugs was effective against large cell neuroendocrine carcinoma metastases, albeit only temporarily. This is the first reported case of large cell neuroendocrine carcinoma with cardiac metastasis.

  15. [Small cell neuroendocrine tumour of the bladder: with reference to a case and bibliographical revision].

    Science.gov (United States)

    Lahoz Tornos, A; Marrón Penón, Maria C; Pardo López, Maria L; Nogueras Gimeno, M A; Pujol Obis, E; Del Villar Sordo, V

    2006-09-01

    The small cell neuroendocrine tumour is an infrecuent neoplasia, with inmunohistochemistry being the key to diagnosis. We present a new case making reference to treatment and its evolution there after. The clinic, diagnosis and treatment of this tumour is described. Bibliographical revision follours. The neuroendocrine tumour of small cell is an infrecuent neoplasia, in which the inmunohistochemistry study is key in the diagnosis. The differential diagnosis includes the high degree diferentiation transitionals cells carcinoma and primary and secondary linfoma. The standard treatment is based on chemotherapy plus surgery.

  16. Survival of egg-laying controlling neuroendocrine cells during reproductive senescence of a mollusc

    NARCIS (Netherlands)

    Janse, C.

    2004-01-01

    During brain aging neuronal degradation occurs. In some neurons this may result in degeneration and cell death, still other neurons may survive and maintain their basic properties. The present study deals with survival of the egg-laying controlling neuroendocrine caudodorsal cells (CDCs) during

  17. Glial-gonadotrophin hormone (GnRH) neurone interactions in the median eminence and the control of GnRH secretion.

    Science.gov (United States)

    Ojeda, S R; Lomniczi, A; Sandau, U S

    2008-06-01

    A wealth of information now exists showing that glial cells are actively involved in the cell-cell communication process generating and disseminating information within the central nervous system. In the hypothalamus, two types of glial cells, astrocytes and ependymal cells lining the latero-ventral portion of the third ventricle (known as tanycytes), regulate the secretory activity of neuroendocrine neurones. This function, initially described for astrocytes apposing magnocellular neurones, has been more recently characterised for neurones secreting gonadotrophin hormone-releasing hormone (GnRH). The available evidence suggests that glial cells of the median eminence regulate GnRH secretion via two related mechanisms. One involves the production of growth factors acting via receptors with tyrosine kinase activity. The other involves plastic rearrangements of glia-GnRH neurone adhesiveness. GnRH axons reach the median eminence, at least in part, directed by basic fibroblast growth factor. Their secretory activity is facilitated by insulin-like growth factor 1 and members of the epidermal growth factor family. A structural complement to these soluble molecules is provided by at least three cell-cell adhesion systems endowed with signalling capabilities. One of them uses the neuronal cell adhesion molecule (NCAM), another employs the synaptic cell adhesion molecule (SynCAM), and the third one consists of neuronal contactin interacting with glial receptor-like protein tyrosine phosphatase-beta. It is envisioned that, within the median eminence, soluble factors and adhesion molecules work coordinately to control delivery of GnRH to the portal vasculature.

  18. [Neuroendocrine tumors of digestive system: morphologic spectrum and cell proliferation (Ki67 index)].

    Science.gov (United States)

    Delektorskaia, V V; Kushliskiĭ, N E

    2013-01-01

    This review deals with the analysis of up-to-date concepts ofdiferent types of human neuroendocrine tumors of the digestive system. It summarizes the information on the specifics of recent histological classifications and criteria of morphological diagnosis accounting histological, ultrastructural and immunohistochemical parameters. Current issues of the nomenclature as well as various systems of grading and staging are discussed. In the light of these criteria the results of the own research clinical value of the determination of cell proliferation in primary and metastatic gastroenteropancreatic neuroendocrine neoplasms on the basis of evaluation of the Ki67 antigen expression are also presented.

  19. Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

    DEFF Research Database (Denmark)

    Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul

    2000-01-01

    in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions. Udgivelsesdato: 2000-Aug...

  20. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  1. Combined choriocarcinoma, neuroendocrine cell carcinoma and tubular adenocarcinoma in the stomach

    Science.gov (United States)

    Hirano, Yasumitsu; Hara, Takuo; Nozawa, Hiroshi; Oyama, Kaeko; Ohta, Naohiro; Omura, Kenji; Watanabe, Go; Niwa, Hideki

    2008-01-01

    We described a patient with adenocarcinoma of the stomach combined with choriocarcinoma and neuroendocrine cell carcinoma. An 85-year-old man visited our hospital because of appetite loss. Gastric fiberscopy revealed a large tumor occupying the cardial region and anterior wall of the gastric body. The patient underwent total gastrectomy with lymphnode dissection and partial resection of the liver. Choriocarcinoma, small cell carcinoma and tubular adenocarcinoma existed in the gastric tumor. The choriocarcinomatous foci contained cells positive for beta-subunit of human chorionic gonadotropin (B-hCG) and human placental lactogen mainly in syncytiotrophoblastic cells. The small cell carcinomatous foci contained cells positive for synaptophysin, neuron-specific enolase (NSE), and chromogranin A. The prognosis for gastric adenocarcinoma with choriocarcinoma and neuroendocrine cell carcinoma is exceedingly poor. This patient died about 2 mo after the first complaint from hepatic failure. This is the first reported case of gastric cancer with these three pathological features. PMID:18506939

  2. Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Spinelli C

    2013-09-01

    Full Text Available Primary neuroendocrine carcinomas of the breast are extremely rare. Neuroendocrine tumors mainly occur in the broncopolmonary system and gastrointestinal tract. The diagnosis of small cell neuroendocrine carcinoma (SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. We are going to describe two cases and to discuss their clinical, radiological and pathological manifestations. Introduction: Neuroendocrine tumors are rare and slow-growing neoplasias derived from neuroendocrine cells. We describe two cases of small cell neuroendocrine carcinoma of the breast and discuss their clinical, radiological and pathological manifestations. Case report: Our patients are two Italian females (38 and 36 year-old with no family history of breast disease. In both cases the diagnosis was confirmed after surgery, when immunohistochemistry revealed a neuroendocrine differentiation of the tumor. The patients are alive and disease free after more than ten years of follow-up. Conclusion: Primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. After surgery, a strict follow-up including octreotide scan should be performed and this doesn’t differ from the one of the usual breast carcinoma.

  3. Notch signaling modulates hypoxia-induced neuroendocrine differentiation of human prostate cancer cells.

    Science.gov (United States)

    Danza, Giovanna; Di Serio, Claudia; Rosati, Fabiana; Lonetto, Giuseppe; Sturli, Niccolò; Kacer, Doreen; Pennella, Antonio; Ventimiglia, Giuseppina; Barucci, Riccardo; Piscazzi, Annamaria; Prudovsky, Igor; Landriscina, Matteo; Marchionni, Niccolò; Tarantini, Francesca

    2012-02-01

    Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation (NED) has been associated with tumor progression, poor prognosis, and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavorable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells in vitro. Exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A, and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent downregulation of Notch-mediated signaling, as shown by reduced levels of the Notch target genes, Hes1 and Hey1. NED was promoted by attenuation of Hes1 transcription, as cells expressing a dominant-negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia downregulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen-independent cell lines, PC-3 and Du145, it did not change the extent of NED in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur. Hypoxia induces NED of LNCaP cells in vitro, which seems to be driven by the inhibition of Notch signaling with subsequent downregulation of Hes1 transcription. ©2011 AACR.

  4. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma

    Science.gov (United States)

    Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F; Louis, Peter; Scott, Sasinya N; Jungbluth, Achim A; Coit, Daniel G; Brownell, Isaac; Busam, Klaus J

    2016-01-01

    Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression. PMID:26022453

  5. Expression of developing neural transcription factors in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).

    Science.gov (United States)

    Escudero, Antonio García; Zarco, Enrique Rodríguez; Arjona, Juan Carlos Girón; Moreno, María José Ríos; Rodríguez, Katherine Gallardo; Benítez, Ana Vallejo; Cámpora, Ricardo González

    2016-09-01

    DIPNECH is characterized by neuroendocrine cell hyperplasia, tumorlets, and eventually carcinoid tumors. Although it is regarded by some authors as a preneoplastic condition, this issue is controversial. New pathologic criteria have recently been proposed for the diagnosis of DIPNECH, and a subgroup of carcinoid tumors expressing developing neural transcription factors (DNTFs), with clinicopathologic features similar to those of DIPNECH, has been recognized. This paper reports on the clinical and pathological findings in three cases of DIPNECH and investigates the expression of three DNTFs (TTF1, ASCL1, and POU3F2). All patients were female, with a mean age of 63 years, and all lesions were located in the periphery of the lung. In two cases, typical carcinoids were associated with a spindle-cell component. All neuroendocrine proliferations were DNTF positive. The morphologic (spindle-cell component), phenotypic (DNTF expression), and clinicopathologic (peripheral tumors, female predominance) similarities suggest that DIPNECH may be a preneoplastic lesion for peripheral carcinoids.

  6. In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonist degarelix on human prostate cell growth.

    Directory of Open Access Journals (Sweden)

    Monica Sakai

    Full Text Available Degarelix is a gonadrotropin-releasing hormone (GnRH receptor (GnRHR antagonist used in patients with prostate cancer who need androgen deprivation therapy. GnRHRs have been found in extra-pituitary tissues, including prostate, which may be affected by the GnRH and GnRH analogues used in therapy. The direct effect of degarelix on human prostate cell growth was evaluated. Normal prostate myofibroblast WPMY-1 and epithelial WPE1-NA22 cells, benign prostatic hyperplasia (BPH-1 cells, androgen-independent PC-3 and androgen-dependent LNCaP prostate cancer cells, as well as VCaP cells derived from a patient with castration-resistant prostate cancer were used. Discriminatory protein and lipid fingerprints of normal, hyperplastic, and cancer cells were generated by matrix-assisted laser desorption/ionization (MALDI mass spectrometry (MS. The investigated cell lines express GNRHR1 and GNRHR2 and their endogenous ligands. Degarelix treatment reduced cell viability in all prostate cell lines tested, with the exception of the PC-3 cells; this can be attributed to increased apoptosis, as indicated by increased caspase 3/7, 8 and 9 levels. WPE1-NA22, BPH-1, LNCaP, and VCaP cell viability was not affected by treatment with the GnRH agonists leuprolide and goserelin. Using MALDI MS, we detected changes in m/z signals that were robust enough to create a complete discriminatory profile induced by degarelix. Transcriptomic analysis of BPH-1 cells provided a global map of genes affected by degarelix and indicated that the biological processes affected were related to cell growth, G-coupled receptors, the mitogen-activated protein kinase (MAPK pathway, angiogenesis and cell adhesion. Taken together, these data demonstrate that (i the GnRH antagonist degarelix exerts a direct effect on prostate cell growth through apoptosis; (ii MALDI MS analysis provided a basis to fingerprint degarelix-treated prostate cells; and (iii the clusters of genes affected by degarelix

  7. Intravenous injection of Evans Blue labels magnocellular neuroendocrine cells of the rat supraoptic nucleus in situ and after dissociation.

    Science.gov (United States)

    Weiss, M L; Cobbett, P

    1992-01-01

    Previous work has demonstrated that intravenous injection of neuronal tracers, e.g. horseradish peroxidase or Fast Blue, can retrogradely label neurons in brain areas that project outside the blood-brain barrier, e.g. magnocellular neuroendocrine neurons of the hypothalamus. Here we have shown that 24 h after intravenous injection of the fluorescent retrograde tracer Evans Blue, the same population of magnocellular neuroendocrine neurons is labeled in the paraventricular, supraoptic and accessory magnocellular nuclei. Parvicellular neuroendocrine cells in the paraventricular nuclei are also labeled. Most Evans Blue-labeled magnocellular neuroendocrine cells in the supraoptic nucleus could be stained immunocytochemically for neurophysins, suggesting that these neurons continue to produce their peptide hormones after taking up the fluorescent dye. Ultrastructural observation of supraoptic cells retrogradely labeled with Evans Blue shows that 95% of the neurons appeared healthy. There was no ultrastructural evidence of degeneration, hyperstimulation, or interruption of the axoplasmic flow. Labeling the neuroendocrine cells with Evans Blue did not alter the size of magnocellular cells, the animal's fluid balance or ingestive behavior. Following enzymatic/mechanical dissociation of the supraoptic nucleus from animals that had been injected with Evans Blue 24 h previously, phase-bright neurons that often contained fluorescent material were observed, thus identifying these neurons as neuroendocrine. Recording from identified neuroendocrine cells showed that these neurons generated spontaneous or current-evoked overshooting action potentials with an afterhyperpolarization and had negative resting membrane potentials. Action potential broadening, a feature of magnocellular neurons, was observed during bursts of action potentials elicited by depolarizing current injection. Taken together, this work would suggest that Evans Blue is non-toxic at the doses used and that it

  8. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia diagnosed by tranbronchoscopic cryoprobe biopsy technique

    OpenAIRE

    Patel, Ravi; Collazo‐Gonzalez, Carolina; Andrews, Arthur; Johnson, Jean; Rumbak, Mark; Smith, Maxwell

    2017-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) remains a poorly understood clinical entity. It is currently classified as a premalignant condition by the World Health Organization (WHO). Symptoms are similar to those associated with obstructive lung disease, including breathlessness and cough. The presentation is often initially ascribed to other diseases such as asthma or chronic obstructive pulmonary disease. Here, we present what we believe is the first described ca...

  9. Primary small cell neuroendocrine carcinoma of the breast: The histogenetic diatribe

    Directory of Open Access Journals (Sweden)

    Cabibi D

    2013-12-01

    Full Text Available The article entitled “Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature” by Spinelli et al. [1]. The authors stated that “the histogenesis is still unclear because the presence of neuroendocrine cells in normal breast has not been proved conclusively”. Moreover they reported two histogenetic hypotheses, the first one stating that “small cell neuroendocrine carcinoma (SCNC is a variant of metaplastic carcinoma arising from a lobular or ductal carcinoma”, the second one claiming that “it is a distinct type of breast carcinoma different from the usual type”. We appreciate this case report and we agree with the authors on the histogenetic diatribe of this rare type of breast neoplasia. In this background, we would highlight our previous case report about a solid variant of mammary adenoid cystic carcinoma merging with "small cell carcinoma" [2] in which we found positivity for CD10 and S100 and negativity for estrogen receptors, both in sbACC and in SCC, in keeping with a myoepithelial origin of both neoplastic areas [3] supporting the hypothesis that the “two components share the same histogenetic myoepithelial origin and represent an example of dedifferentiation along neuroendocrine phenotype lines occurring in a multipotential neoplastic stem line, already committed towards a myoepithelial phenotype”. These findings are in keeping with the first hypothesis about the metaplastic, divergent histogenetic nature of SNSC and we think that this rare SNSC, albeit arising from a different tumor, could be introduced in this case review of the literature, also for its contribute to the histogenetic diatribe.

  10. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  11. Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases

    Directory of Open Access Journals (Sweden)

    Chisato Ohe, MD

    2014-09-01

    Full Text Available Chromophobe renal cell carcinoma (ChRCC with neuroendocrine differentiation/morphology (NED/NEM is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years. One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases; in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.

  12. Current Concepts in Neuroendocrine Disruption

    Science.gov (United States)

    2014-01-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  13. A case of large cell neuroendocrine carcinoma of the bladder with prolonged spontaneous remission.

    Science.gov (United States)

    Chong, Vincent; Zwi, Jonathan; Hanning, Fritha; Lim, Remy; Williams, Andrew; Cadwallader, Jon

    2017-05-01

    Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder are rare. We present a case of a 72-year-old man who presented with back pain and acute renal failure. Ultrasound showed a soft tissue mass in the base of the bladder causing bilateral ureteric obstruction. Subsequent biopsy of this mass demonstrated neuroendocrine carcinoma. He was commenced on neoadjuvant chemotherapy (carboplatin/etoposide) and proceeded to a radical cysto-prostatectomy. Histology revealed a LCNEC involving the bladder, T4a with invasion through to adipose tissue and posteriorly at perivesical resection margins. In addition, there was a Gleason score 9 prostatic adenocarcinoma, distinct from the neuroendocrine carcinoma. Following surgery, the patient developed gross local-regional recurrence and refused further systemic therapy. However, 1 year following referral to palliative care, a further CT-PET showed complete spontaneous remission of his disease. There are only few case reports of LCNEC of the urinary bladder therefore the pathogenesis and treatment protocol are still unclear. This case report highlights the unpredictable nature of this disease.

  14. Postembryonic proliferation of neuroendocrine cells expressing adipokinetic hormone peptides in the corpora cardiaca of the locust.

    Science.gov (United States)

    Kirschenbaum, S R; O'Shea, M

    1993-08-01

    Neuroendocrine glands that synthesize and secrete peptide hormones regulate the levels of these peptide messengers during development. In this article we describe a mechanism for regulating neuropeptide levels in the corpora cardiaca of the locust Schistocerca gregaria, a neuroendocrine gland structurally analogous to the vertebrate adenohypophysis. A set of five colocalized peptide hormones of the adipokinetic hormone family is synthesized in intrinsic neurosecretory cells in the corpora cardiaca. During postembryonic development there are progressive changes in the absolute and relative levels of these five peptide hormones. We show that the ability of the gland to increase peptide synthesis is due to a 100-fold increase in the number of cells which make up the gland. The gland grows by the addition of new cells derived from symmetrical division of undifferentiated precursor cells within the corpora cardiaca. We show, using double-label immunocytochemistry, that cells born in the glandular lobe mature into cells that express adipokinetic hormone peptides. The pattern of cell birth and peptide expression can account for the dramatic increase in postembryonic peptide levels.

  15. Treatment Option Overview (Pancreatic Neuroendocrine Tumors / Islet Cell Tumors)

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  16. Neuroendocrine regulation of frog adrenocortical cells by neurotensin

    NARCIS (Netherlands)

    Sicard, F.; D, D.E.G.; Gras, M.; Leprince, J.; Conlon, J.M.; Roubos, E.W.; Vaudry, H.; Delarue, C.

    2005-01-01

    We previously characterized the primary structure of neurotensin (NT) from an extract of the intestine of the frog Rana esculenta. In this study, we provide evidence for the involvement of NT in the neurocrine regulation of the secretory activity of frog adrenocortical cells. Immunohistochemical

  17. Functional Implications of Neuroendocrine Differentiated Cells in Prostate Cancer

    NARCIS (Netherlands)

    J. Jongsma (Johan)

    2000-01-01

    textabstractThis thesis focuses on NE differentiation in prostate cancer, especially in prostate cancer models. We studied the effects of androgen depletion on the NE differentiated status of in vivo and in vitro prostatic tumor models. Knowledge concerning the function of NE cells in the normal

  18. Somatic currents contribute to frequency-dependent spike-broadening in supraoptic neuroendocrine cells.

    Science.gov (United States)

    O'Regan, M H; Cobbett, P

    1993-10-29

    Voltage-gated K and Ca currents were recorded in acutely dissociated neuroendocrine cells of the supraoptic nucleus. The effect of repeated activation of the currents by trains of (10) voltage pulses over a range of pulse-repetition frequencies were examined. There was a significant reduction of K-current amplitude and a significant increase of Ca-current amplitude during trains with high repetition frequencies. Frequency-dependent changes in K and Ca conductances may contribute to frequency-dependent spike-broadening which is exhibited during bursts of action potentials generated by these neurons.

  19. The Function of Neuroendocrine Cells in Prostate Cancer

    Science.gov (United States)

    2013-04-01

    with 10% fetal bovine serum , 2 mM L-glutamine, penicillin (100 U/ml), and streptomycin (100 mg/ml) in a humidified atmosphere of 5% CO2 maintained at 37...cells were in McCoy’s 5Amedium, and all were supplementedwith 10% fetal calf serum , 2 mM glutamine, penicillin, and streptomycin at 37 °C with 5% CO2...mortality risk and decreased serum prostate specific antigen. J Urol 2010;184:2303–7. 2. Andriole GL, Crawford ED, Grubb RL III, Buys SS, Chia D, Church TR

  20. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion.

    Science.gov (United States)

    Barrios, Juliana; Patel, Kruti R; Aven, Linh; Achey, Rebecca; Minns, Martin S; Lee, Yoonjoo; Trinkaus-Randall, Vickery E; Ai, Xingbin

    2017-09-01

    Pulmonary neuroendocrine cells (PNECs) are the only innervated airway epithelial cells. To what extent neural innervation regulates PNEC secretion and function is unknown. Here, we discover that neurotrophin 4 (NT4) plays an essential role in mucus overproduction after early life allergen exposure by orchestrating PNEC innervation and secretion of GABA. We found that PNECs were the only cellular source of GABA in airways. In addition, PNECs expressed NT4 as a target-derived mechanism underlying PNEC innervation during development. Early life allergen exposure elevated the level of NT4 and caused PNEC hyperinnervation and nodose neuron hyperactivity. Associated with aberrant PNEC innervation, the authors discovered that GABA hypersecretion was required for the induction of mucin Muc5ac expression. In contrast, NT4-/- mice were protected from allergen-induced mucus overproduction and changes along the nerve-PNEC axis without any defects in inflammation. Last, GABA installation restored mucus overproduction in NT4-/- mice after early life allergen exposure. Together, our findings provide the first evidence for NT4-dependent neural regulation of PNEC secretion of GABA in a neonatal disease model. Targeting the nerve-PNEC axis may be a valid treatment strategy for mucus overproduction in airway diseases, such as childhood asthma.-Barrios, J., Patel, K. R., Aven, L., Achey, R., Minns, M. S., Lee, Y., Trinkaus-Randall, V. E., Ai, X. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion. © FASEB.

  1. Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

    KAUST Repository

    Moritz, Tom

    2016-02-05

    The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long-branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer.

  2. Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

    Science.gov (United States)

    Papa, Anselmo; Rossi, Luigi; Verrico, Monica; Di Cristofano, Claudio; Moretti, Valentina; Strudel, Martina; Zoratto, Federica; Minozzi, Marina; Tomao, Silverio

    2017-09-01

    The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. © 2015 John Wiley & Sons Ltd.

  3. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples

    Directory of Open Access Journals (Sweden)

    Alessandro Tanca

    2016-06-01

    Full Text Available Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs. Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%. MS data are available in the PeptideAtlas repository at http://www.peptideatlas.org/PASS/PASS00375.

  4. NEUROECTODERMAL TUMORS OF THE PERIPHERAL AND THE CENTRAL-NERVOUS-SYSTEM SHARE NEUROENDOCRINE N-CAM-RELATED ANTIGENS WITH SMALL-CELL LUNG CARCINOMAS

    NARCIS (Netherlands)

    MOLENAAR, WM; DELEIJ, L; TROJANOWSKI, JQ

    1991-01-01

    The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize "neural/neuroendocrine" or "neural" antigens, as defined by their reaction pattern in normal

  5. Benign Endometrial Polyp and Primary Endometrial Small Cell Neuroendocrine Carcinoma Confined to the Polyp: A Rare Association

    Directory of Open Access Journals (Sweden)

    Pembe Oltulu

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs are a heterogeneous group of tumoral lesions originating from diffuse endo­crine system cells. They occur mostly in the gastrointes­tinal system and the lung. Primary NETs of the female reproductive tract are rare. In a widely used classification, primary small cell neuroendocrine carcinomas (SCNECs and large cell neuroendocrine carcinomas (LCNECs of the endometrium were included in a subgroup of poorly differentiated neuroendocrine carcinomas. SCNECs of the endometrium are very rare and they are often com­bined with other epithelial neoplasms. Their myometrial and extrauterine invasions are common during the initial diagnosis due to their aggressive behaviors. In this ar­ticle, we present a rare case of primary endometrial SC­NEC detected within the benign endometrial polyp and without invasion of myometrium and extrauterine tissues in a 70-year-old female patient presenting with post­menopausal bleeding. Histopathologically, the tumor cells showed positive staining with Synaptophysin, the Ki-67 labeling index was 80-90%, the mitotic index was 15/10 per HPF and there was no necrosis and lymphovascular invasion. J Clin Exp Invest 2016; 7 (1: 107-110

  6. Gene expression signatures of neuroendocrine prostate cancer and primary small cell prostatic carcinoma.

    Science.gov (United States)

    Tsai, Harrison K; Lehrer, Jonathan; Alshalalfa, Mohammed; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L

    2017-11-13

    Neuroendocrine prostate cancer (NEPC) may be rising in prevalence as patients with advanced prostate cancer potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. While prior studies comparing NEPC and prostatic adenocarcinoma have identified important candidates for targeted therapy, most have relied on few NEPC patients due to disease rarity, resulting in thousands of differentially expressed genes collectively and offering an opportunity for meta-analysis. Moreover, past studies have focused on prototypical NEPC samples with classic immunohistochemistry profiles, whereas there is increasing recognition of atypical phenotypes. In the primary setting, small cell prostatic carcinoma (SCPC) is frequently admixed with adenocarcinomas that may be clonally related, and a minority of SCPCs express markers typical of prostatic adenocarcinoma while rare cases do not express neuroendocrine markers. We derived a meta-signature of prototypical high-grade NEPC, then applied it to develop a classifier of primary SCPC incorporating disease heterogeneity. Prototypical NEPC samples from 15 patients across 6 frozen tissue microarray datasets were assessed for genes with consistent outlier expression relative to adenocarcinomas. Resulting genes were used to determine subgroups of primary SCPCs (N=16) and high-grade adenocarcinomas (N=16) profiled by exon arrays using formalin-fixed paraffin-embedded (FFPE) material from our institutional archives. A subgroup classifier was developed using differential expression for feature selection, and applied to radical prostatectomy cohorts. Sixty nine and 375 genes demonstrated consistent outlier expression in at least 80% and 60% of NEPC patients, with close resemblance in expression between NEPC and small cell lung cancer. Clustering by these genes generated 3 subgroups among primary samples from our institution. Nearest centroid classification based on the predominant phenotype from each

  7. Circadian Control of the Estrogenic Circuits Regulating GnRH Secretion and the Preovulatory Luteinizing Hormone Surge

    Directory of Open Access Journals (Sweden)

    Lance J Kriegsfeld

    2012-05-01

    Full Text Available Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary-gonadal (HPG axis functioning. In mammals, the master circadian pacemaker in the suprachaismatic nucleus (SCN of the anterior hypothalamus coordinates reproductively-relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the GnRH system in control of the preovulatory LH surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge.

  8. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia diagnosed by tranbronchoscopic cryoprobe biopsy technique

    Science.gov (United States)

    Patel, Ravi; Collazo‐Gonzalez, Carolina; Johnson, Jean; Rumbak, Mark; Smith, Maxwell

    2017-01-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) remains a poorly understood clinical entity. It is currently classified as a premalignant condition by the World Health Organization (WHO). Symptoms are similar to those associated with obstructive lung disease, including breathlessness and cough. The presentation is often initially ascribed to other diseases such as asthma or chronic obstructive pulmonary disease. Here, we present what we believe is the first described case of DIPNECH diagnosed by transbronchoscopic cryoprobe biopsy. The patient presented with chronic cough, dyspnoea, pulmonary function tests consistent with obstruction, and a computed tomography (CT) scan of chest with multiple nodules. The patient went on to have transbronchoscopic cryoprobe biopsies of the lung, which confirmed the diagnosis of DIPNECH. PMID:29026608

  9. Voltage-clamp recordings from identified dissociated neuroendocrine cells of the adult rat supraoptic nucleus.

    Science.gov (United States)

    Cobbett, P; Weiss, M L

    1990-06-01

    In vitro intracellular recordings of membrane potential obtained from the oxytocin and vasopressin neurons of the mammalian hypothalamo-neurohypophysial system in slices (1-3) and expiants (4, 5) have demonstrated many of the intrinsic properties of these magnocellular neuroendocrine cells (MNCs). Voltage-clamp techniques, which are required to study directly the currents underlying intrinsic or transmitter-evoked potential changes, have been applied to cultured embryonic (6) or neonatal supraoptic neurons (7-9) and have been successfully applied to adult supraoptic neurons in situ in only one laboratory (10, 11). We have modified a technique for dissociation of viable adult guineapig hippocampal neurons (12) to dissociate supraoptic MNCs from adult rats for voltage-clamp studies. MNCs were selectively labelled with a fluorescent dye in vivo so that they could be identified after dissociation and prior to making recordings. These data have been published in abstract form elsewhere (13, 14).

  10. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia of the Lung (DIPNECH): Current Best Evidence.

    Science.gov (United States)

    Wirtschafter, Eric; Walts, Ann E; Liu, Sandy T; Marchevsky, Alberto M

    2015-10-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.

  11. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

    Directory of Open Access Journals (Sweden)

    Sangbin Park

    2011-08-01

    Full Text Available Drosophila neuroendocrine cells comprising the corpora cardiaca (CC are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

  12. Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm is regulated by Notch signaling.

    Science.gov (United States)

    Park, Sangbin; Bustamante, Erika L; Antonova, Julie; McLean, Graeme W; Kim, Seung K

    2011-08-01

    Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.

  13. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  14. [Inhibitory effects of Notch1 overexpression on proliferation and neuroendocrine marker expression in a small cell lung cancer cell line].

    Science.gov (United States)

    Wang, Jie-Xin; Zhang, Xiu-ming; Wang, Ling-ling; Cheng, Hui; Yao, Gen-you

    2009-05-01

    To investigate the effects of Notch1 signal activation on proliferation and neuroendocrine marker expression in small cell lung cancer cells. The active form of Notch1 (NIC) was over-expressed in NCI-H446 cells by constitutive transfection and a stable transfected cell line was established. Proliferation of NCI-H446 cells was analysed by MTT assay on 6 successive days. Expression of neuroendocrine markers (CgA, NSE) was observed by immunohistochemistry and Western blot analysis. Statistical analysis was conducted to compare the results in cells with NIC transfected and those in control groups. MTT assay showed that absorbance (A) of cells overexpressing Notch1 was significantly depressed compared with that of the control cells (PNIC transfected group, sham group and negative control group were 8.81 +/- 0.77, 38.10 +/- 1.55, 38.97 +/- 0.80, respectively, the former one was significantly smaller than that of the latter two (PNIC transfected group, sham group and negative control group were 7.21 +/- 0.59, 28.25 +/- 1.46, 30.57 +/- 1.31, respectively, the former one was significantly smaller than that in the latter two (PNIC transfected group and sham group were 0.54 +/- 0.03 and 0.99 +/- 0.05, respectively, (gray scale of the negative control set as 1.00), the former one was significantly smaller than that of the other two groups (PNIC transfected group and sham group were 0.43 +/- 0.02 and 1.07 +/- 0.09, respectively (gray scale of the negative control set as 1.00), the former one was significantly smaller than that of the other two groups (P<0.01). Notch1 may behave as a tumor suppressor in small cell lung cancer. Notch1 signal activation can inhibit the proliferation and neuroendocrine marker expression in small cell lung cancer cells, suggesting that Notch1 gene could be a new target for small cell lung cancer treatment and probable relief of paraneoplastic syndrome.

  15. Acute damage by naphthalene triggers expression of the neuroendocrine marker PGP9.5 in airway epithelial cells

    DEFF Research Database (Denmark)

    Poulsen, T.T.; Naizhen, X.; Linnoila, R.I.

    2008-01-01

    Protein Gene Product 9.5 (PGP9.5) is highly expressed in nervous tissue. Recently PGP9.5 expression has been found to be upregulated in the pulmonary epithelium of smokers and in non-small cell lung cancer, suggesting that it also plays a role in carcinogen-inflicted lung epithelial injury...... neuroendocrine markers was found in the non-neuroendocrine epithelial cells after naphthalene exposure. In contrast, immunostaining for the cell cycle regulator p27(Kip1), which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27(Kip1) in naphthalene exposed...... and further strengthens the accumulating evidence of PGP9.5 as a central player in lung epithelial damage and early carcinogenesis Udgivelsesdato: 2008/9/26...

  16. Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

    Directory of Open Access Journals (Sweden)

    John Wysocki

    2014-01-01

    Full Text Available Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC. Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas.

  17. The influences of GnRH, oxytocin and vasoactive intestinal peptide on LH and PRL secretion by porcine pituitary cells in vitro.

    Science.gov (United States)

    Bogacka, I; Siawrys, G; Okrasa, S; Kaminski, T; Przala, J

    2002-09-01

    The aim of the present study was to evaluate the possible direct effects of GnRH, oxytocin (OT) and vasoactive intestinal peptide (VIP) on the release of LH and PRL by dispersed porcine anterior pituitary cells. Pituitary glands were obtained from mature gilts, which were ovariectomized (OVX) one month before slaughter. Gilts randomly assigned to one of the four groups were treated: in Group 1 (n = 8) with 1 ml/100 kg b.w. corn oil (placebo); in Group 2 (n = 8) and Group 3 (n = 8) with estradiol benzoate (EB) at the dose 2.5 mg/100 kg b.w., respectively, 30-36 h and 60-66 h before slaughter; and in Group 4 (n = 9) with progesterone (P4) at the dose 120 mg/ 100 kg b.w. for five consecutive days before slaughter. In gilts of Group 2 and Group 3 treatments with EB have induced the negative and positive feedback in LH secretion, respectively. Isolated anterior pituitary cells (10(6)/well) were cultured in McCoy's 5a medium with horse serum and fetal calf serum for 3 days at 37 degrees C under the atmosphere of 95% air and 5% CO2. Subsequently, the culture plates were rinsed with fresh McCoy's 5A medium and the cells were incubated for 3.5 h at 37 degrees C in the same medium containing one of the following agents: GnRH (100 ng/ml), OT (10-1000 nM) or VIP (1-100 nM). The addition of GnRH to cultured pituitary cells resulted in marked increases in LH release (p gilts representing the positive feedback phase (Group 3). In contrast, OT and VIP were without any effect on LH release in Group 1 (placebo) and Group 2 (the negative feedback). Pituitary cells obtained from OVX gilts primed with P4 produced significantly higher amounts (p gilts of all experimental groups. Oxytocin also failed to alter PRL secretion in Group 1 and Group 2. However, pituitary cells from animals primed with EB 60-66 h before slaughter and P4 produced markedly increased amounts of PRL in the presence of OT. Neuropeptide VIP stimulated PRL release from pituitary cells of OVX gilts primed with EB

  18. A Network Model of the Periodic Synchronization Process in the Dynamics of Calcium Concentration in GnRH Neurons

    Science.gov (United States)

    2013-01-01

    Mathematical neuroendocrinology is a branch of mathematical neurosciences that is specifically interested in endocrine neurons, which have the uncommon ability of secreting neurohormones into the blood. One of the most striking features of neuroendocrine networks is their ability to exhibit very slow rhythms of neurosecretion, on the order of one or several hours. A prototypical instance is that of the pulsatile secretion pattern of GnRH (gonadotropin releasing hormone), the master hormone controlling the reproductive function, whose origin remains a puzzle issue since its discovery in the seventies. In this paper, we investigate the question of GnRH neuron synchronization on a mesoscopic scale, and study how synchronized events in calcium dynamics can arise from the average electric activity of individual neurons. We use as reference seminal experiments performed on embryonic GnRH neurons from rhesus monkeys, where calcium imaging series were recorded simultaneously in tens of neurons, and which have clearly shown the occurrence of synchronized calcium peaks associated with GnRH pulses, superposed on asynchronous, yet oscillatory individual background dynamics. We design a network model by coupling 3D individual dynamics of FitzHugh–Nagumo type. Using phase-plane analysis, we constrain the model behavior so that it meets qualitative and quantitative specifications derived from the experiments, including the precise control of the frequency of the synchronization episodes. In particular, we show how the time scales of the model can be tuned to fit the individual and synchronized time scales of the experiments. Finally, we illustrate the ability of the model to reproduce additional experimental observations, such as partial recruitment of cells within the synchronization process or the occurrence of doublets of synchronization. PMID:23574739

  19. Perifosine-mediated Akt inhibition in neuroendocrine tumor cells: role of specific Akt isoforms.

    Science.gov (United States)

    Zitzmann, Kathrin; Vlotides, George; Brand, Stephan; Lahm, Harald; Spöttl, Gerald; Göke, Burkhard; Auernhammer, Christoph J

    2012-06-01

    The majority of neuroendocrine tumors (NETs) of the gastroenteropancreatic system show aberrant Akt activity. Several inhibitors of the phosphoinositide 3-kinase (PI(3)K)-Akt-mTOR signaling pathway are currently being evaluated in clinical phase II and III studies for the treatment of NETs with promising results. However, the molecular mechanisms and particularly the role of different Akt isoforms in NET signaling are not fully understood. In this study, we examine the effect of Akt inhibition on NET cells of heterogeneous origin. We show that the Akt inhibitor perifosine effectively inhibits Akt phosphorylation and cell viability in human pancreatic (BON1), bronchus (NCI-H727), and midgut (GOT1) NET cells. Perifosine treatment suppressed the phosphorylation of Akt downstream targets such as GSK3α/β, MDM2, and p70S6K and induced apoptosis. To further investigate the role of individual Akt isoforms for NET cell function, we specifically blocked Akt1, Akt2, and Akt3 via siRNA transfection. In contrast to Akt2 knockdown, knockdown of Akt isoforms 1 and 3 decreased phosphorylation levels of GSK3α/β, MDM2, and p70S6K and suppressed NET cell viability and colony-forming capacity. The inhibitory effect of simultaneous downregulation of Akt1 and Akt3 on tumor cell viability was significantly stronger than that caused by downregulation of all Akt isoforms, suggesting a particular role for Akt1 and Akt3 in NET signaling. Akt3 siRNA-induced apoptosis while all three isoform-specific siRNAs impaired BON1 cell invasion. Together, our data demonstrate potent antitumor effects of the pan-Akt inhibitor perifosine on NET cells in vitro and suggest that selective targeting of Akt1 and/or Akt3 might improve the therapeutic potential of Akt inhibition in NET disease.

  20. Physiology of the gonadotrophin-releasing hormone (GnRH) neurone: studies from embryonic GnRH neurones.

    Science.gov (United States)

    Constantin, S

    2011-06-01

    Gonadotrophin-releasing hormone (GnRH)-secreting neurones are the final output of the central nervous system driving fertility in all mammals. Although it has been known for decades that the efficiency of communication between the hypothalamus and the pituitary depends on the pulsatile profile of GnRH secretion, how GnRH neuronal activity is patterned to generate pulses at the median eminence is unknown. To date, the scattered distribution of the GnRH cell bodies remains the main limitation to assessing the cellular events that could lead to pulsatile GnRH secretion. Taking advantage of the unique developmental feature of GnRH neurones, the nasal explant model allows primary GnRH neurones to be maintained within a micro-network where pulsatile secretion is preserved and where individual cellular activity can be monitored simultaneously across the cell population. This review summarises the data obtained from work using this in vitro model, and brings some insights into GnRH cellular physiology. © 2011 The Author. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  1. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome.

    Science.gov (United States)

    Elsenbruch, Sigrid; Lucas, Ayscha; Holtmann, Gerald; Haag, Sebastian; Gerken, Guido; Riemenschneider, Natalie; Langhorst, Jost; Kavelaars, Annemieke; Heijnen, Cobi J; Schedlowski, Manfred

    2006-10-01

    Augmented neuroendocrine stress responses and altered immune functions may play a role in the manifestation of functional gastrointestinal (GI) disorders. We tested the hypothesis that IBS patients would demonstrate enhanced psychological and endocrine responses, as well as altered stress-induced redistribution of circulating leukocytes and lymphocytes, in response to an acute psychosocial stressor when compared with healthy controls. Responses to public speaking stress were analyzed in N = 17 IBS patients without concurrent psychiatric conditions and N = 12 healthy controls. At baseline, immediately following public speaking, and after a recovery period, state anxiety, acute GI symptoms, cardiovascular responses, serum cortisol and plasma adrenocorticotropic hormone (ACTH) were measured, and numbers of circulating leukocytes and lymphocyte subpopulations were analyzed by flow cytometry. Public speaking led to significant cardiovascular activation, a significant increase in ACTH, and a redistribution of circulating leukocytes and lymphocyte subpopulations, including significant increases in natural killer cells and cytotoxic/suppressor T cells. IBS patients demonstrated significantly greater state anxiety both at baseline and following public speaking. However, cardiovascular and endocrine responses, as well as the redistribution of circulating leukocytes and lymphocyte subpopulations after public speaking stress, did not differ for IBS patients compared with controls. In IBS patients without psychiatric comorbidity, the endocrine response as well as the circulation pattern of leukocyte subpopulations to acute psychosocial stress do not differ from healthy controls in spite of enhanced emotional responses. Future studies should discern the role of psychopathology in psychological and biological stress responses in IBS.

  2. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    INTRODUCTION. Neuroendocrine tumors comprise heterogeneous group of neoplasms which originate from endocrine cells, both within endocrine organs and within the cells of diffuse endocrine system. These tumors have vari- able clinical behavior ranging from well-differentiated, slow growing tumors to ...

  3. Clinical analysis of 50 Eastern Asian patients with primary pulmonary large-cell neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang XK

    2015-05-01

    Full Text Available Xin-ke Zhang,1,* Tao Qin,1,* Yin-duo Zeng,1,2,* Yuan-yuan Zhao,1 Xue Hou,1 Wen-feng Fang,1 Shao-dong Hong,1 Ting Zhou,1 Zhi-huang Hu,1 Yun-peng Yang,1 Yu-xiang Ma,1 Cong Xue,1 Yan Huang,1 Hong-yun Zhao,1 Li Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: To understand the clinicopathological features of patients with primary pulmonary large-cell neuroendocrine carcinoma (LCNEC, including the frequency of epidermal growth factor receptor (EGFR mutation, and to explore prognostic factors.Methods: We investigated a cohort of 50 individuals from our center database who were diagnosed with operable pulmonary LCNEC and treated in Sun Yat-sen University Cancer Center. Serum albumin (ALB and neuron-specific enolase (NSE were also collected. Survival curves were obtained with the Kaplan–Meier method, and the differences between groups in survival were tested by the log-rank test.Results: The median age was 59 years (range, 40–80 years. Fourteen patients underwent mutational analysis of EGFR; of these, 12 had wild-type EGFR and the remaining two had EGFR mutations in exons. The median disease-free survival (DFS of pulmonary LCNEC was 49.3 months and that of overall survival (OS was not reached. DFS and OS were shorter for patients with decreased serum ALB than for patients with normal serum ALB (P=0.003 and P=0.004, respectively. Meanwhile, a high level of NSE was also significantly associated with short DFS and OS (P=0.005 and P=0.000, respectively. Multivariate analysis showed that decrease in serum ALB was an independent prognostic factor for OS (P=0.046.Conclusion: The frequency of EGFR mutation in LCNEC patients is low. Serum ALB and NSE levels are

  4. Oligophrenin-1 Connects Exocytotic Fusion to Compensatory Endocytosis in Neuroendocrine Cells.

    Science.gov (United States)

    Houy, Sébastien; Estay-Ahumada, Catherine; Croisé, Pauline; Calco, Valérie; Haeberlé, Anne-Marie; Bailly, Yannick; Billuart, Pierre; Vitale, Nicolas; Bader, Marie-France; Ory, Stéphane; Gasman, Stéphane

    2015-08-05

    Oligophrenin-1 (OPHN1) is a protein with multiple domains including a Rho family GTPase-activating (Rho-GAP) domain, and a Bin-Amphiphysin-Rvs (BAR) domain. Involved in X-linked intellectual disability, OPHN1 has been reported to control several synaptic functions, including synaptic plasticity, synaptic vesicle trafficking, and endocytosis. In neuroendocrine cells, hormones and neuropeptides stored in large dense core vesicles (secretory granules) are released through calcium-regulated exocytosis, a process that is tightly coupled to compensatory endocytosis, allowing secretory granule recycling. We show here that OPHN1 is expressed and mainly localized at the plasma membrane and in the cytosol in chromaffin cells from adrenal medulla. Using carbon fiber amperometry, we found that exocytosis is impaired at the late stage of membrane fusion in Ophn1 knock-out mice and OPHN1-silenced bovine chromaffin cells. Experiments performed with ectopically expressed OPHN1 mutants indicate that OPHN1 requires its Rho-GAP domain to control fusion pore dynamics. On the other hand, compensatory endocytosis assessed by measuring dopamine-β-hydroxylase (secretory granule membrane) internalization is severely inhibited in Ophn1 knock-out chromaffin cells. This inhibitory effect is mimicked by the expression of a truncated OPHN1 mutant lacking the BAR domain, demonstrating that the BAR domain implicates OPHN1 in granule membrane recapture after exocytosis. These findings reveal for the first time that OPHN1 is a bifunctional protein that is able, through distinct mechanisms, to regulate and most likely link exocytosis to compensatory endocytosis in chromaffin cells. Copyright © 2015 the authors 0270-6474/15/3511045-11$15.00/0.

  5. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

    Science.gov (United States)

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-02-16

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

  6. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract

    Directory of Open Access Journals (Sweden)

    Yu Yu Thar

    2016-01-01

    Full Text Available Small cell neuroendocrine carcinoma (SNEC is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

  7. Pancreatic neuroendocrine cell tumor secreting parathyroid hormone-related protein and gastrin: Report of a case.

    Science.gov (United States)

    Morita, Yoshifumi; Suzuki, Shohachi; Sakaguchi, Takanori; Oishi, Kosuke; Suzuki, Atsushi; Fukumoto, Kazuhiko; Inaba, Keisuke; Baba, Satoshi; Takehara, Yasuo; Konno, Hiroyuki

    2010-12-01

    This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy.

  8. Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Diez Soraya

    2010-03-01

    Full Text Available Abstract Background Wnt-11 is a secreted protein that modulates cell growth, differentiation and morphogenesis during development. We previously reported that Wnt-11 expression is elevated in hormone-independent prostate cancer and that the progression of prostate cancer from androgen-dependent to androgen-independent proliferation correlates with a loss of mutual inhibition between Wnt-11- and androgen receptor-dependent signals. However, the prevalence of increased expression of Wnt-11 in patient tumours and the functions of Wnt-11 in prostate cancer cells were not known. Results Wnt-11 protein levels in prostate tumours were determined by immunohistochemical analysis of prostate tumour tissue arrays. Wnt-11 protein was elevated in 77/117 of tumours when compared with 27 benign prostatic hypertrophy specimens and was present in 4/4 bone metastases. In addition, there was a positive correlation between Wnt-11 expression and PSA levels above 10 ng/ml. Androgen-depleted LNCaP prostate cancer cells form neurites and express genes associated with neuroendocrine-like differentiation (NED, a feature of prostate tumours that have a poor prognosis. Since androgen-depletion increases expression of Wnt-11, we examined the role of Wnt-11 in NED. Ectopic expression of Wnt-11 induced expression of NSE and ASCL1, which are markers of NED, and this was prevented by inhibitors of cyclic AMP-dependent protein kinase, consistent with the known role of this kinase in NED. In contrast, Wnt-11 did not induce NSE expression in RWPE-1 cells, which are derived from benign prostate, suggesting that the role of Wnt-11 in NED is specific to prostate cancer. In addition, silencing of Wnt-11 expression in androgen-depleted LNCaP cells prevented NED and resulted in apoptosis. Silencing of Wnt-11 gene expression in androgen-independent PC3 cells also reduced expression of NSE and increased apoptosis. Finally, silencing of Wnt-11 reduced PC3 cell migration and ectopic

  9. Targeted Mutagenesis of the Hypophysiotropic Gnrh3 in Zebrafish (Danio rerio Reveals No Effects on Reproductive Performance.

    Directory of Open Access Journals (Sweden)

    Olivia Smith Spicer

    Full Text Available Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form function in zebrafish (Danio rerio to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis. Using the TALEN technology, we developed a gnrh3-/- zebrafish line that harbors a 62 bp deletion in the gnrh3 gene. Our gnrh3-/- zebrafish line represents the first targeted and heritable mutation of a Gnrh isoform in any organism. Using immunohistochemistry, we verified that gnrh3-/- fish do not possess Gnrh3 peptide in any regions of the brain. However, other than changes in mRNA levels of pituitary gonadotropin genes (fshb, lhb, and cga during early development, which are corrected by adulthood, there were no changes in ontogeny and reproduction in gnrh3-/- fish. The gnrh3-/- zebrafish are fertile, displaying normal gametogenesis and reproductive performance in males and females. Together with our previous results that Gnrh3 cell ablation causes infertility, these results indicate that a compensatory mechanism is being activated, which is probably primed early on upon Gnrh3 neuron differentiation and possibly confined to Gnrh3 neurons. Potential compensation factors and sensitive windows of time for compensation during development and puberty should be explored.

  10. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

    Directory of Open Access Journals (Sweden)

    Sparrow Malcolm P

    2005-10-01

    Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  11. Insulin/IGF-regulated size scaling of neuroendocrine cells expressing the bHLH transcription factor Dimmed in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jiangnan Luo

    Full Text Available Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS. By targeted genetic manipulations of insulin receptor (dInR expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM. Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B, whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin signaling components, such as Rheb (small GTPase, TOR and S6K (S6 kinase. After Dimm-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of Dimm. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.

  12. Pulmonary Neuroendocrine Cell Hyperplasia in Hemoglobin Bart-induced Hydrops Fetalis: A model for Chronic Intrauterine Hypoxia.

    Science.gov (United States)

    Taweevisit, Mana; Theerasantipong, Boochit; Taothong, Kanlaya; Thorner, Paul Scott

    2017-01-01

    The pulmonary neuroendocrine system includes pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) that are distributed throughout respiratory epithelium and regulate lung growth and maturation antenatally. Abnormalities in this system have been linked to many hypoxia-associated pediatric pulmonary disorders. Hemoglobin (Hb) Bart disease is a severe form of α-thalassemia resulting in marked intrauterine hypoxia with hydrops fetalis (HF) and usually death in utero. Affected fetuses can serve as a naturally occurring human model for the effects of intrauterine hypoxia, and we postulated that these effects should include changes in the pulmonary neuroendocrine system. Bombesin immunostaining was used to assess PNECs and NEBs in stillborn fetuses with Hb Bart HF ( n = 16) and with HF from other causes ( n = 14) in comparison to non-HF controls. Hb Bart HF showed a significant increase in the proportion of PNECs in respiratory epithelium ( P = .002), mean number of NEB nuclei ( P = .03), and mean size of NEBs ( P = .002), compared to normal non-HF controls. Significant differences were not observed between HF due to other causes and non-HF controls with normal lungs. Non-HF controls with pulmonary hypoplasia showed significant increases in PNECs compared to HF cases not due to Hb Bart HF, implying HF alone does not cause such increases. In contrast, no significant differences were noted between non-HF controls with pulmonary hypoplasia and Hb Bart cases. Hb Bart HF may provide a useful model for studying the pulmonary neuroendocrine system under chronic intrauterine hypoxia.

  13. Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258 and its Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Shalini S. Yadav

    2017-06-01

    Full Text Available Prostate cancer (PCa remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT; however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC. With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC. This, along with previous observations of an increase in the number of such NE cells in aggressive tumors, has been suggested as a mechanism of resistance development during prostate cancer progression. Dovitinib (TKI-258/CHIR-258 is a pan receptor tyrosine kinase (RTK inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It has shown efficacy in mouse-model of PCa bone metastasis, and is presently in clinical trials for several cancers. We observed that both androgen receptor (AR positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. The NE differentiation was also observed when mice harboring PC3-xenografted tumors were systemically treated with Dovitinib. The mechanistic underpinnings of this differentiation are unclear, but seem to be supported through MAPK-, PI3K-, and Wnt-signaling pathways. Further elucidation of the differentiation process will enable the identification of alternative salvage or combination therapies to overcome the potential resistance development.

  14. EFFECT OF INVIVO PRETREATMENT WITH ESTRADIOL AND EITHER GNRH, GNRH AGONISTIC ANALOG OR GNRH ANTAGONISTIC ANALOG ON GNRH-STIMULATED SECRETION OF LH INVITRO

    NARCIS (Netherlands)

    SCHUILING, GA; KOITER, TR; MOES, H

    1991-01-01

    In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting

  15. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia in a patient with multiple pulmonary nodules: case report and literature review

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    Yamin HS

    2017-12-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare pulmonary disease, where carcinoid tumorlets invade the pulmonary parenchyma and bronchioles. These nests of cells release a variety of mediators including bombesin and gastrin releasing peptide that cause heterogeneous bronchoconstriction, creating a mosaic appearance on chest imaging studies, especially on expiratory scans. Clinically patients usually have long standing symptoms of shortness of breath (SOB and cough that are difficult to distinguish from asthma. In this article we describe a case of DIPNECH in a patient with several years’ history of SOB and cough, and review 179 cases of DIPNECH reported in the literature since 1992.

  16. Gonadotropin-releasing hormone (GnRH) agonist triptorelin inhibits estradiol-induced serum response element (SRE) activation and c-fos expression in human endometrial, ovarian and breast cancer cells.

    Science.gov (United States)

    Gründker, Carsten; Günthert, Andreas R; Hellriegel, Martin; Emons, Günter

    2004-11-01

    The majority of human endometrial (>80%), ovarian (>80%) and breast (>50%) cancers express GnRH receptors. Their spontaneous and epidermal growth-factor-induced proliferation is dose- and time-dependently reduced by treatment with GnRH and its agonists. In this study, we demonstrate that the GnRH agonist triptorelin inhibits estradiol (E2)-induced cancer cell proliferation. The proliferation of quiescent estrogen receptor alpha (ER alpha)-/ER beta-positive, but not of ER alpha-negative/ER beta-positive endometrial, ovarian and breast cancer cell lines, was significantly stimulated (P<0.001) (ANOVA) after treatment with E2 (10(-8) M). This effect was time- and dose-dependently antagonized by simultaneous treatment with triptorelin. The inhibitory effect was maximal at 10(-5) M concentration of triptorelin (P<0.001). In addition, we could show that, in ER alpha-/ER beta-positive cell lines, E2 induces activation of serum response element (SRE) and expression of the immediate early-response gene c-fos. These effects were blocked by triptorelin (P<0.001). E2-induced activation of estrogen-response element (ERE) was not affected by triptorelin. The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.

  17. Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

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    Christian Cortés-Campos

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

  18. Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

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    Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

    2011-06-01

    Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

  19. Neuroendocrine Tumor, diagnostic difficulties

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    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  20. The prognostic influence of neuroendocrine cells in prostate cancer: Results of a long-term follow-up study with patients treated by radical prostatectomy

    NARCIS (Netherlands)

    M.A. Noordzij (Marinus); Th.H. van der Kwast (Theo); G.J. van Steenbrugge (Gert Jan); W.C.J. Hop (Wim); F.H. Schröder (Fritz)

    1995-01-01

    textabstractThe distribution of immunohistochemically defined neuroen-docrine (NE) cells in benign, pre-cancerous and neoplastic prostatic tissues and the prognostic value of these cells in prostate cancer were studied in the radical prostatectomy specimens of 90 patients from whom complete

  1. CD200 Expression in Neuroendocrine Neoplasms.

    Science.gov (United States)

    Love, Jason E; Thompson, Kimberly; Kilgore, Mark R; Westerhoff, Maria; Murphy, Claire E; Papanicolau-Sengos, Antonios; McCormick, Kinsey A; Shankaran, Veena; Vandeven, Natalie; Miller, Faith; Blom, Astrid; Nghiem, Paul T; Kussick, Steven J

    2017-09-01

    CD200 expression has been well studied in hematopoietic malignancies; however, CD200 expression has not been well-characterized in neuroendocrine neoplasms. We examined CD200 expression in 391 neuroendocrine neoplasms from various anatomic sites. Tissue blocks containing pulmonary small cell carcinoma, pulmonary carcinoid, large cell neuroendocrine carcinoma, pancreatic neuroendocrine tumor, gastrointestinal carcinoid, and Merkel cell carcinoma were evaluated for CD200 expression by immunohistochemistry. A set of nonneuroendocrine carcinomas was stained for comparison. CD200 was expressed in 87% of the neuroendocrine neoplasms studied, including 60 of 72 (83%) pulmonary small cell carcinomas, 15 of 22 (68%) pulmonary carcinoids, three of four (75%) pulmonary large cell neuroendocrine carcinomas, 125 of 146 (86%) Merkel cell carcinomas, 79 of 83 (95%) gastrointestinal luminal carcinoids, and 56 of 60 (93%) pancreatic neuroendocrine tumors. Thirty-two of 157 (20%) nonneuroendocrine carcinomas expressed CD200. In gastrointestinal carcinoid and pancreatic neuroendocrine neoplasms, CD200 negativity correlated with higher grade. CD200 is a relatively sensitive marker of neuroendocrine neoplasms and represents a potential therapeutic target in these difficult-to-treat malignancies.

  2. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  3. Primary small-cell neuroendocrine carcinoma of the male breast: a rare case report with review of the literature

    Directory of Open Access Journals (Sweden)

    Jiang J

    2014-05-01

    Full Text Available Jian Jiang,1 Guixin Wang,1 Li Lv,2 Caigang Liu,1 Xi Liang,1 Haidong Zhao11Department of Breast Surgery, 2Department of Pathology, the Second Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of ChinaAbstract: In this case study and review, we present a case of a primary small-cell neuroendocrine carcinoma (SCNC of the male breast. Primary SCNC of the breast is a rare tumor with less than 30 cases reported in the literature. Most cases are found in women. Another exceptional point is that human epidermal growth factor receptor-2 (Her-2 immunoreactivity was positive in our recent case, which differed to previous reports detailing SCNC in women. We have no evidence to demonstrate the differences between treatment and prognoses for males and females, because we do not have sufficient cases to undertake an evidence-based investigation. We provide this rare case history; review the literature on SCNC of the breast; and discuss detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, surgical and adjuvant treatment, and prognosis.Keywords: small-cell carcinoma, SMCC, neuroendocrine, male breast cancer, SCNC neoplasm

  4. Neuroendocrine breast cancer.

    Science.gov (United States)

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-08-13

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast lump. Physical examination, mammography and ultrasonography showed a 2.4 cm nodule, probably a benign lesion (BI-RADS 3). A fine needle aspiration biopsy was performed and revealed proliferative epithelial papillary lesion. She was submitted to excisional biopsy and histology showed endocrine breast cancer well differentiated (G1). Immunohistochemically, tumour cells were positive for synaptophysin. These breast cancers are characterised for their excellent prognosis and conservative treatment is almost always enough to obtain patient cure.

  5. Immune-Neuroendocrine Interactions and Autoimmune Diseases

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    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  6. Neuroendocrine Role for VGF

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    Jo Edward Lewis

    2015-02-01

    Full Text Available The vgf gene (non-acronymic is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain derived neurotrophic factor, and glial derived growth factor. The VGF gene gives rise to a 68kDa precursor polypeptide which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific pro-hormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly the hypothalamus and hippocampus, and in peripheral tissues including the pituitary gland, the adrenal glands and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles and in this mini-review we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction and cognition.

  7. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Wagner, Ludwig; Brandt Sørensen, Flemming

    2005-01-01

    , synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas...

  8. Small cell neuroendocrine carcinoma of tracheostomy site in a patient with a history of juvenile laryngeal papillomatosis.

    Science.gov (United States)

    Violet Wilmot, Victoria; Nixon, Iain James; Nixon, Ioanna Fragkandrea

    2016-08-09

    Juvenile laryngeal papillomatosis is the commonest cause of benign epithelial tumours of the larynx. Following diagnostic biopsy, surgical debulking is the mainstay of therapy. The condition is often recurrent with further papillomas forming after debridement, requiring serial procedures and occasionally demanding tracheostomy. Rarely, the disease can undergo malignant transformation; most commonly to squamous cell carcinoma. We describe the first reported case of small cell neuroendocrine carcinoma occurring in the previous tracheostomy site of a 29-year-old male with a history of juvenile laryngeal papillomatosis. The patient, with a background of multiple treatments for juvenile papillomas, presented with voice change, breathing difficultly and erythema at the site of previous tracheostomy. Induction chemotherapy followed by chemoradiation was used to treat the lesion with a good response to initial therapy. 2016 BMJ Publishing Group Ltd.

  9. Characterization of Gnrh/Gnih elements in the olfacto-retinal system and ovary during zebrafish ovarian maturation.

    Science.gov (United States)

    Corchuelo, Sheryll; Martinez, Emanuel R M; Butzge, Arno J; Doretto, Lucas B; Ricci, Juliana M B; Valentin, Fernanda N; Nakaghi, Laura S O; Somoza, Gustavo M; Nóbrega, Rafael H

    2017-07-15

    Gonadotropin releasing hormone (GnRH) is one of the key players of brain-pituitary-gonad axis, exerting overall control over vertebrate reproduction. In zebrafish, two variants were characterized and named as Gnrh2 and Gnrh3. In this species, Gnrh3, the hypohysiotropic form, is expressed by neurons of the olfactory-retinal system, where it is related with food detection, intra/interspecific recognition, visual acuity and retinal processing modulation. Previous studies have reported the presence of Gnrh receptors in the zebrafish retina, but not yet in the zebrafish olfactory epithelium. The current study analyzed the presence of gnrh2 and gnrh3, their receptors (gnrhr 1,2,3 and 4) and gnih (gonadotropin inhibitory hormone) transcripts, as well as the Gnrh3 protein in the olfactory epithelium (OE), olfactory bulb (OB), retina and ovary during zebrafish ovarian maturation. We found an increase of gnrh receptors transcripts in the OE at the final stages of ovarian maturation. In the OE, Gnrh3 protein was detected in the olfactory receptor neurons cilia and in the olfactory nerve fibers. Interestingly, in the OB, we found an inverse expression pattern between gnih and gnrh3. In the retina, gnrhr4 mRNA was found in the nuclei of amacrine, bipolar, and ganglion cells next to Gnrh3 positive fibers. In the ovary, gnrh3, gnrhr2 and gnrhr4 transcripts were found in perinucleolar oocytes, while gnih in oocytes at the cortical alveolus stage. Our results suggested that Gnrh/Gnih elements are involved in the neuromodulation of the sensorial system particularly at the final stages of maturation, playing also a paracrine role in the ovary. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. HPV positive neuroendocrine cervical cancer cells are dependent on Myc but not E6/E7 viral oncogenes

    Science.gov (United States)

    Yuan, Hang; Krawczyk, Ewa; Blancato, Jan; Albanese, Christopher; Zhou, Dan; Wang, Naidong; Paul, Siddartha; Alkhilaiwi, Faris; Palechor-Ceron, Nancy; Dakic, Aleksandra; Fang, Shuang; Choudhary, Sujata; Hou, Tung-Wei; Zheng, Yun-Ling; Haddad, Bassem R.; Usuda, Yukari; Hartmann, Dan; Symer, David; Gillison, Maura; Agarwal, Seema; Wangsa, Danny; Ried, Thomas; Liu, Xuefeng; Schlegel, Richard

    2017-01-01

    Using conditional cell reprogramming, we generated a stable cell culture of an extremely rare and aggressive neuroendocrine cervical cancer. The cultured cells contained HPV-16, formed colonies in soft agar and rapidly produced tumors in immunodeficient mice. The HPV-16 genome was integrated adjacent to the Myc gene, both of which were amplified 40-fold. Analysis of RNA transcripts detected fusion of the HPV/Myc genes, arising from apparent microhomologous recombination. Spectral karyotyping (SKY) and fluorescent-in-situ hybridization (FISH) demonstrated coordinate localization and translocation of the amplified Myc and HPV genes on chromosomes 8 and 21. Similar to the primary tumor, tumor cell cultures expressed very high levels of the Myc protein and, in contrast to all other HPV-positive cervical cancer cell lines, they harbored a gain-of-function mutation in p53 (R273C). Unexpectedly, viral oncogene knockdown had no effect on the growth of the cells, but it did inhibit the proliferation of a conventional HPV-16 positive cervical cancer cell line. Knockdown of Myc, but not the mutant p53, significantly inhibited tumor cell proliferation. On the basis of these data, we propose that the primary driver of transformation in this aggressive cervical cancer is not HPV oncogene expression but rather the overexpression of Myc. PMID:28378747

  11. Primary Small Cell Neuroendocrine Carcinoma of the Nasal Cavity After Successful Curative Therapy of Nasopharyngeal Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Chien-Heng Lin

    2009-03-01

    Full Text Available Patients with head and neck cancer have a greater risk of developing second primary malignant neoplasms than patients with any other type of malignancy. Small cell neuroendocrine carcinoma (SNEC mainly occurs in the lung, and is rarely found in the head and neck region. Only a few cases of sinonasal SNEC have been reported in the English literature. A woman aged 53 years, who had undergone successful curative radiotherapy for nasopharyngeal carcinoma 10 years earlier, presented with a history of bleeding from the left nostril for several weeks. A computed tomography scan of the head and neck showed a mass in the left nasal cavity with extension into the maxillary sinus. A biopsy specimen was taken and pathology revealed SNEC. The patient underwent a full course of concurrent chemoradiotherapy. No local recurrence or distant metastasis was noted during the 12 months of follow-up.

  12. Controle sobre GnRH durante o anestro pós-parto em bovinos GnRH control during bovine postpartum anestrous

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    João Francisco Coelho de Oliveira

    2010-12-01

    Full Text Available O pós-parto em bovinos é caracterizado como um momento em que as fêmeas bovinas não ovulam, principalmente devido a uma inadequada liberação de gonadotrofinas. Os conceitos e os mecanismos regulatórios do hormônio liberador de gonadotrofinas (GnRH têm sido descritos isoladamente. Esta revisão aborda a influência da nutrição e amamentação, com enfoque na regulação do GnRH, e fornece conceitos atuais do controle neuroendocrinológico da secreção de GnRH durante o pós-parto em bovinos. Conhecimentos atuais das funções do hormônio inibitório de gonadotrofinas (GnIH, da leptina, dos estrógenos, da kisspeptina e da adiponectina, bem como suas complexas inter-relações durante este período estão detalhados para melhor entendimento do assunto.The bovine postpartum period is characterized as a moment when the ovulation is suppressed, mainly in consequence of insufficient release of gonadotropins. Concepts and regulatory mechanisms of gonadotropin-releasing hormone (GnRH had been described independently. This review covers the influence of nutrition and suckling with emphasis on GnRH regulation, and provides up to date concepts of neuroendocrine control of GnRH secretion during postpartum in cattle. Current knowledge of gonadotropin-inhibitory hormone (GnIH, leptin, estrogens and kisspeptin during this period are presented in order to provide a better understanding of the subject.

  13. Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

    Science.gov (United States)

    Meehan, R. T.

    1986-01-01

    Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

  14. Neuroendocrine Cell Carcinoma of Unknown Primary Arising in Long Standing History of Multiple Sclerosis

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    Stergios Boussios

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease that targets myelinated axons in the central nervous system (CNS. Cancer of unknown primary site (CUP is a well-recognised clinical disorder, accounting for 3–5% of all malignant epithelial tumors. CUP is clinically characterised as an aggressive disease with early dissemination. Studies of cancer risk in MS patients have shown inconsistent findings. An increased risk of malignancy in patients with MS has been suggested, but recently serious questions have been raised regarding this association. Use of disease-modifying therapies might contribute to an increased cancer risk in selected MS patients. The concurrence of MS and CUP is exceptionally rare. Here we describe the case of a neuroendocrine carcinoma of unknown primary diagnosed in a male patient with a nine-year history of MS. The discussion includes data from all available population-based register studies with estimates of certain malignancies in patients with MS.

  15. [Nontraditional "large-cell" neuroendocrine formations (accessory nuclei) in the brain of Anamnia and Amniota].

    Science.gov (United States)

    Grinevich, V V; Polenov, A L; Danilova, O A; Kuzik, V V; Romanova, I V

    1995-01-01

    Using immunochemical PAP-method nonapeptidergic neuroendocrine formations in the hypothalamus and adjacent brain areas of fishes (the sterlet Acipenser ruthenus, the shark Scylliorhinus canicula), amphibians (the frog Rana temporaria), reptiles (the snake Natrix natrix), mammals (rats and dogs) and human have been studied. In Amniota and human accessory nuclei (AN) in addition to main "magnocellular" nuclei (supraoptic, postoptic and paraventricular) were discovered. Two AN, circular and dorsolateral ones, were found in snakes, and circular, dorsolateral, forniceal and extrahypothalamic AN were revealed in rat, dog and human brain. In Anamnia, sharks and frogs, in contrast to sterlets, the dorsolateral sub-nucleus inside preoptic nucleus was identified. AN similarity in the phylogenetic row of vertebrates and mechanisms of AN creation in phylo- and ontogenesis were discussed.

  16. Autophagy pathway is required for IL-6 induced neuroendocrine differentiation and chemoresistance of prostate cancer LNCaP cells.

    Directory of Open Access Journals (Sweden)

    Pei-Ching Chang

    Full Text Available Prostate cancer (PCa cells undergoing neuroendocrine differentiation (NED are clinically relevant to the development of relapsed castration-resistant PCa. Increasing evidences show that autophagy involves in the development of neuroendocrine (NE tumors, including PCa. To clarify the effect of autophagy on NED, androgen-sensitive PCa LNCaP cells were examined. Treatment of LNCaP cells with IL-6 resulted in an induction of autophagy. In the absence of androgen, IL-6 caused an even stronger activation of autophagy. Similar result was identified in NED induction. Inhibition of autophagy with chloroquine (CQ markedly decreased NED. This observation was confirmed by beclin1 and Atg5 silencing experiments. Further supporting the role of autophagy in NED, we found that LC3 was up-regulated in PCa tissue that had relapsed after androgen-deprivation therapy when compared with their primary tumor counterpart. LC3 staining in relapsed PCa tissue showed punctate pattern similar to the staining of chromogranin A (CgA, a marker for NED cells. Moreover, autophagy inhibition induced the apoptosis of IL-6 induced NE differentiated PCa cells. Consistently, inhibition of autophagy by knockdown of beclin1 or Atg5 sensitized NE differentiated LNCaP cells to etoposide, a chemotherapy drug. To identify the mechanisms, phosphorylation of IL-6 downstream targets was analyzed. An increase in phospho-AMPK and a decrease in phospho-mTOR were found, which implies that IL-6 regulates autophagy through the AMPK/mTOR pathway. Most important to this study is the discovery of REST, a neuronal gene-specific transcriptional repressor that is involved in autophagy activation. REST was down-regulated in IL-6 treatment. Knockdown experiments suggest that REST is critical to NED and autophagy activation by IL-6. Together, our studies imply that autophagy is involved in PCa progression and plays a cytoprotective role when NED is induced in PCa cells by IL-6 treatment. These results

  17. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

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    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  18. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  19. A methodology for distinguishing divergent cell fates within a common progenitor population: adenoma- and neuroendocrine-like cells are confounders of rat ileal epithelial cell (IEC-18 culture

    Directory of Open Access Journals (Sweden)

    Paxton Jessica B

    2005-01-01

    Full Text Available Abstract Background IEC-18 cells are a non-transformed, immortal cell line derived from juvenile rat ileal crypt cells. They may have experimental advantages over tumor-derived gastrointestinal lineages, including preservation of phenotype, normal endocrine responses and retention of differentiation potential. However, their proclivity for spontaneous differentiation / transformation may be stereotypical and could represent a more profound experimental confounder than previously realized. We hypothesized that IEC-18 cells spontaneously diverge towards a uniform mixture of epigenetic fates, with corresponding phenotypes, rather than persist as a single progenitor lineage. Results IEC-18 cells were cultured for 72 hours in serum free media (SFM, with and without various insulin-like growth factor agonists to differentially boost the basal rate of proliferation. A strategy was employed to identify constitutive genes as markers of divergent fates through gene array analysis by cross-referencing fold-change trends for individual genes against crypt cell abundance in each treatment. We then confirmed the cell-specific phenotype by immunolocalization of proteins corresponding to those genes. The majority of IEC-18 cells in SFM alone had a loss in expression of the adenomatous polyposis coli (APC gene at the mRNA and protein levels, consistent with adenoma-like transformation. In addition, a small subset of cells expressed the serotonin receptor 2A gene and had neuroendocrine-like morphology. Conclusions IEC-18 cells commonly undergo a change in cell fate prior to reaching confluence. The most common fate switch that we were able to detect correlates with a down regulation of the APC gene and transformation into an adenoma-like phenotype.

  20. Midgut neuroendocrine tumor presenting with acute intestinal ischemia.

    Science.gov (United States)

    Mantzoros, Ioannis; Savvala, Natalia Antigoni; Ioannidis, Orestis; Parpoudi, Styliani; Loutzidou, Lydia; Kyriakidou, Despoina; Cheva, Angeliki; Intzos, Vasileios; Tsalis, Konstantinos

    2017-12-07

    Neuroendocrine tumors represent a heterogeneous group of neoplasms that arise from neuroendocrine cells and secrete various peptides and bioamines. While gastrointestinal neuroendocrine tumors, commonly called carcinoids, account for about 2/3 of all neuroendocrine tumors, they are relatively rare. Small intestine neuroendocrine tumors originate from intestinal enterochromaffin cells and represent about 1/4 of small intestine neoplasms. They can be asymptomatic or cause nonspecific symptoms, which usually leads to a delayed diagnosis. Imaging modalities can aid diagnosis and surgery remains the mainstay of treatment. We present a case of a jejunal neuroendocrine tumor that caused nonspecific symptoms for about 1 year before manifesting with acute mesenteric ischemia. Abdominal X-rays revealed pneumatosis intestinalis and an abdominal ultrasound and computed tomography confirmed the diagnosis. The patient was submitted to segmental enterectomy. Histopathological study demonstrated a neuroendocrine tumor with perineural and arterial infiltration and lymph node metastasis. The postoperative course was uneventful and the patient denied any adjuvant treatment.

  1. The novel Raf inhibitor Raf265 decreases Bcl-2 levels and confers TRAIL-sensitivity to neuroendocrine tumour cells.

    Science.gov (United States)

    Zitzmann, Kathrin; de Toni, Enrico; von Rüden, Janina; Brand, Stephan; Göke, Burkhard; Laubender, Rüdiger P; Auernhammer, Christoph J

    2011-04-01

    The tumour-selective death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for the treatment of human cancer. However, many tumours have evolved mechanisms to resist TRAIL-induced apoptosis. A number of studies have demonstrated that aberrant PI(3)K-Akt-mTOR survival signalling may confer TRAIL resistance by altering the balance between pro- and anti-apoptotic proteins. Here, we show that neuroendocrine tumour (NET) cell lines of heterogeneous origin exhibit a range of TRAIL sensitivities and that TRAIL sensitivity correlates with the expression of FLIP(S), caspase-8, and Bcl-2. Neither single mTOR inhibition by everolimus nor dual mTOR/PI(3)K inhibition by NVP-BEZ235 was able to enhance TRAIL susceptibility in any of the tested cell lines. In contrast, dual PI(3)K-Akt-mTOR and Raf-MEK-Erk pathway inhibition by the IGF-1R inhibitor NVP-AEW541 effectively restored TRAIL sensitivity in NCI-H727 bronchus carcinoid cells. Furthermore, blocking Raf-MEK-Erk signalling by the novel Raf inhibitor Raf265 significantly enhanced TRAIL sensitivity in NCI-H727 and CM insulinoma cells. While having no effect on FLIP(S) or caspase-8 expression, Raf265 strongly decreased Bcl-2 levels in those cell lines susceptible to its TRAIL-sensitizing action. Taken together, our findings suggest that combinations of Raf-MEK-Erk pathway inhibitors and TRAIL might offer a novel therapeutic strategy in NET disease.

  2. The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.

    Science.gov (United States)

    Morell, C; Bort, A; Vara, D; Ramos-Torres, A; Rodríguez-Henche, N; Díaz-Laviada, I

    2016-09-01

    Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer. The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells. NE differentiation of prostate cancer LNCaP cells was induced by serum deprivation or by incubation with interleukin-6, for 6 days. Levels of NE markers and signaling proteins were determined by western blotting. Levels of cannabinoid receptors were determined by quantitative PCR. The involvement of signaling cascades was investigated by pharmacological inhibition and small interfering RNA. The differentiated LNCaP cells exhibited neurite outgrowth, and increased the expression of the typical NE markers neuron-specific enolase and βIII tubulin (βIII Tub). Treatment with 3 μM WIN inhibited NK differentiation of LNCaP cells. The cannabinoid WIN downregulated the PI3K/Akt/mTOR signaling pathway, resulting in NE differentiation inhibition. In addition, an activation of AMP-activated protein kinase (AMPK) was observed in WIN-treated cells, which correlated with a decrease in the NE markers expression. Our results also show that during NE differentiation the expression of cannabinoid receptors CB1 and CB2 dramatically decreases. Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.

  3. Functional Significance of GnRH and Kisspeptin, and Their Cognate Receptors in Teleost Reproduction

    Directory of Open Access Journals (Sweden)

    RENJITHA eGOPURAPPILLY

    2013-03-01

    Full Text Available Guanine nucleotide binding protein (G-protein-coupled receptors (GPCRs are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs. Kisspeptin (Kiss1 and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R, have recently been identified as a critical signalling system in the control of reproduction. The Kiss1/GPR54 system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signalling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signalling mechanisms, ligand interactions and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and will consider their physiological significance in the control of reproduction.

  4. Functional Significance of GnRH and Kisspeptin, and Their Cognate Receptors in Teleost Reproduction

    Science.gov (United States)

    Gopurappilly, Renjitha; Ogawa, Satoshi; Parhar, Ishwar S.

    2012-01-01

    Guanine nucleotide binding protein (G-protein)-coupled receptors (GPCRs) are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH) represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs). Kisspeptin (Kiss1) and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R), have recently been identified as a critical signaling system in the control of reproduction. The Kiss1/Kiss-R system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signaling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signaling mechanisms, ligand interactions, and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and consider their physiological significance in the control of reproduction. PMID:23482509

  5. Regulation versus modulation in GnRH receptor function

    Energy Technology Data Exchange (ETDEWEB)

    Zolman, J.C.; Theodoropoulos, T.J.

    1985-03-01

    Serum luteinizing hormone (LH) concentration after exposure to gonadotropin-releasing hormone (GnRH) indicates that an instantaneous increase occurs in the rate of release of LH directly from the anterior pituitary, as measured dynamically during superfusion in vitro. On the other hand, estradiol-17 beta (E2) alone shows no such instantaneous effect on LH release rate (at least for the first four hours), in either physiologic or pharmacologic concentrations. At the same time, brief (ten to 30 minute) exposure of isolated anterior pituitary plasma membranes to physiologic concentrations of E2 significantly alters the binding of a fully biologically active /sup 125/I-GnRH to its plasma membrane receptor protein. In order to characterize the effect of E2 on GnRH binding further, dispersed bovine anterior pituitary cells were preincubated for six hours in the presence or absence of physiologic concentrations of E2 (10(-10)M). Following preincubation in the presence of E2, the cell suspension was incubated for 30 minutes with physiologic concentrations (5 x 10(-11) - 5 x 10(-10)M) of a fully biologically active /sup 125/I-GnRH. The treatment, at least, doubled the number of biologically important high affinity GnRH binding sites (Kd's . 7.5 x -10(-11) - 4.5 x 10(-10)M), and changed the binding capacity of some of the binding sites up to three fold, which altered the cooperativity of GnRH-receptor interaction. Thus, the interaction of E2 with GnRH at the level of GnRH receptor is mandatory for the short-term pituitary effect of E2 on LH release in vitro and in vivo.

  6. Up-Regulated Expression of LAMP2 and Autophagy Activity during Neuroendocrine Differentiation of Prostate Cancer LNCaP Cells.

    Science.gov (United States)

    Morell, Cecilia; Bort, Alicia; Vara-Ciruelos, Diana; Ramos-Torres, Ágata; Altamirano-Dimas, Manuel; Díaz-Laviada, Inés; Rodríguez-Henche, Nieves

    2016-01-01

    Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells. Using cDNA microarrays, we compared gene expression profiles of NE cells and non-differentiated LNCaP cells. We identified up-regulation of 155 genes, among them LAMP2, a lysosomal membrane protein involved in lysosomal stability and autophagy. We then confirmed up-regulation of LAMP2 in NE cells by qRT-PCR, Western blot and confocal microscopy assays, showing that mRNA up-regulation correlated with increased levels of LAMP2 protein. Subsequently, we determined autophagy activity in NE cells by assessing the protein levels of SQSTM/p62 and LC3 by Western blot and LC3 and Atg5 mRNAs content by qRT-PCR. The decreased levels of SQSTM/p62 was accompanied by an enhanced expression of LC3 and ATG5, suggesting activation of autophagy in NE cells. Blockage of autophagy with 1μM AKT inhibitor IV, or by silencing Beclin 1 and Atg5, prevented NE cell differentiation, as revealed by decreased levels of the NE markers. In addition, AKT inhibitor IV as well as Beclin1 and Atg5 kwockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these results suggest that LAMP2 overexpression assists NE differentiation of LNCaP cells induced by serum deprivation and facilitates autophagy activity in order to attain the NE phenotype and cell survival. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer.

  7. [Neuroendocrine neoplasms of the breast].

    Science.gov (United States)

    Anlauf, M; Neumann, M; Bomberg, S; Luczak, K; Heikaus, S; Gustmann, C; Antke, C; Ezziddin, S; Fottner, C; Pavel, M; Pape, U-F; Rinke, A; Lahner, H; Schott, M; Cremer, B; Hörsch, D; Baum, R P; Groh, U; Alkatout, I; Rudlowski, C; Scheler, P; Zirbes, T K; Hoffmann, J; Fehm, T; Gabbert, H E; Baldus, S E

    2015-05-01

    Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

  8. Estrogenic Regulation of the GnRH Neuron

    Directory of Open Access Journals (Sweden)

    Sally eRadovick

    2012-04-01

    Full Text Available Reproductive function is regulated by the secretion of luteinizing hormone (LH and follicle-stimulating hormone (FSH from the pituitary and the steroid hormones from the gonads. The dynamic changes in the levels of the reproductive hormones regulate secondary sex characteristics, gametogenesis, cellular function and behavior. Hypothalamic GnRH neurons, with cell bodies located in the basal hypothalamus, represent the final common pathway for neuronally derived signals to the pituitary. As such, they serve as integrators of a dizzying array of signals including sensory inputs mediating information about circadian, seasonal, behavioral, pheromonal and emotional cues. Additionally, information about peripheral physiological function may also be included in the integrative signal to the GnRH neuron. These signals may communicate information about metabolic status, disease or infection. Gonadal steroid hormones arguably exert the most important effects on GnRH neuronal function. In both males and females, the gonadal steroid hormones exert negative feedback regulation on axis activity at both the level of the pituitary and the hypothalamus. These negative feedback loops regulate homeostasis of steroid hormone levels. In females, a cyclic reversal of estrogen feedback produces a positive feedback loop at both the hypothalamic and pituitary levels. Central positive feedback results in a dramatic increase in GnRH secretion (Sisk and others 2001; Clarke 1993; Moenter, Brand and Karsch 1992; Xia and others 1992. This is coupled with an increase in pituitary sensitivity to GnRH (Turzillo, DiGregorio and Nett 1995; Savoy-Moore and others 1980, which produces the massive surge in secretion of LH that triggers ovulation.

  9. 1α,25(OH)2D3Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Metastasis After VEGF-A Stimulation.

    Science.gov (United States)

    Chiang, Kun-Chun; Yeh, Chun-Nan; Pang, Jong-Hwei S; Hsu, Jun-Te; Yeh, Ta-Sen; Chen, Li-Wei; Kuo, Sheng-Fong; Takano, Masashi; Chen, Tai C; Kittaka, Atsushi; Hsieh, Po-Jen; Juang, Horng-Heng

    2017-11-01

    Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an advanced stage. Most patients with PanNETs die of metastasis. Vascular endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2α-(3-hydroxypropyl)-1α,25(OH) 2 D 3 ], a 1α,25-dihydroxy-vitamin D3 (1α,25(OH) 2 D 3 ) analog, on PanNET cell metastasis after VEGF-A stimulation. Migration and invasion assays, western blot, and immunofluorescent staining were applied in this study. VEGF-A increased PanNET cell migration and invasion, which was attenuated by 1α,25(OH) 2 D 3 and MART-10. VEGF-A treatment stimulated epithelial-mesenchymal transition (EMT) of PanNET cells. During this process, expression of snail family transcriptional repressor 1 and 2, and fibronectin was up-regulated. 1α,25(OH) 2 D 3 and MART-10 counteracted VEGF-A-induced EMT. In addition, expression of neuropilin 1, a key protein in VEGF-A signaling, was down-regulated by 1α,25(OH) 2 D 3 and MART-10. Furthermore, synthesis of F-actin was increased by VEGF-A and reduced by 1α,25(OH) 2 D 3 and MART-10. Our data indicate that MART-10 could be deemed a promising drug for PanNET treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Class-C SOX Transcription Factors Control GnRH Gene Expression via the Intronic Transcriptional Enhancer

    Science.gov (United States)

    Kim, Hee-Dae; Choe, Han Kyoung; Chung, Sooyoung; Kim, Myungjin; Seong, Jae Young

    2011-01-01

    GnRH is a pivotal hypothalamic neurohormone governing reproduction and sexual development. Because transcriptional regulation is crucial for the spatial and temporal expression of the GnRH gene, a region approximately 3.0 kb upstream of the mammalian GnRH promoter has been extensive studied. In the present study, we demonstrate a transcription-enhancer located in the first intron (intron A) region of the GnRH gene. This transcriptional enhancer harbors putative sex-determining region Y-related high-mobility-group box (SOX) family transcription factor-binding sites, which are well conserved across many mammalian species. The class-C SOX member proteins (SOX-C) (SOX4 and SOX11) specifically augment this transcriptional activation by binding to these SOX-binding sites. In accordance, SOX11 is highly enriched in immortalized GnRH-producing GT1-1 cells, and suppression of its expression significantly decreases GnRH gene expression as well as GnRH secretion. Chromatin immunoprecipitation shows that endogenous SOX-C factors recognize and bind to the intronic enhancer in GT1-1 cells and the hypothalamus. Accompanying immunohistochemical analysis demonstrates that SOX4 or SOX11 are highly expressed in the majority of hypothalamic GnRH neurons in adult mice. Taken together, these findings demonstrate that SOX-C transcription factors function as important transcriptional regulators of cell type-specific GnRH gene expression by acting on the intronic transcriptional enhancer. PMID:21527504

  11. Renal cell carcinoma metastasizing to pancreatic neuroendocrine neoplasm - the second case described in the world literature.

    Science.gov (United States)

    Bednarek-Rajewska, Katarzyna; Zalewski, Przemysław; Bręborowicz, Danuta; Woźniak, Aldona

    Tumor-to-tumor metastases are very rare events. We report a case of a 64-year-old man who presented with a tumor of the pancreas. The patient underwent partial pancreatectomy. Frozen section diagnosis of the tumor was an endocrine neoplasm. Paraffin block slide examination revealed a tumor consisting of two components: pancreatic endocrine neoplasm at the periphery of the tumor and the central part composed of clear cells with delicate vessels. The results of immunohistochemical stains revealed renal cell carcinoma surrounded by pancreatic endocrine neoplasm, therefore representing an unusual case of renal cell carcinoma metastasizing to a pancreatic endocrine neoplasm.

  12. The GnRH Pulse Generator

    Directory of Open Access Journals (Sweden)

    Pasha Grachev

    2016-12-01

    Full Text Available The pulsatile secretion of hormones is an efficient way of coding a large variety of chemical messages. The GnRH pulse pattern determines which gonadotropin is released when and at what concentration, prescribing a detailed set of instructions to the gonads that produce changes in the steroid hormone milieu. Although GnRH neurons possess some inherent rhythmicity, they are diffusely situated within the hypothalamus and in isolation are only capable of generating physiologically irrelevant messages, hence a synchronization module exists upstream. The identity of the neural unit comprising the GnRH pulse generator is now generally thought to include KNDy neurons in the arcuate nucleus. These neurons coexpress the neuropeptides kisspeptin, neurokinin B and dynorphin A, as well as other transmitters, and are in intimate contact with the GnRH network. The GnRH pulse generator’s function is the precise control of GnRH neuron excitability, coordinated activation, stimulation of neurosecretory events, modulation of gene transcription and the mediation of the negative feedback effect of gonadal steroids. Additionally, the GnRH pulse generator is an ideal venue for the integration of various sensory and homeostatic cues that regulate reproductive functions. In this chapter we provide a historical perspective of the elegant science that sparked interest in the central mechanisms underlying the functions of the reproductive system, explain how hypotheses surrounding GnRH pulse generation have evolved and describe the current state of knowledge within the dynamic field of GnRH pulse generator research.

  13. In vitro regulation of LH biosynthesis and release by GnRH and estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Ramey, J.W.

    1986-01-01

    Anterior pituitaries were taken from female rats at random stages of the estrous cycle, enzymatically dispersed, and cultured for 48h in steroid-free ..cap alpha..-modified Eagles medium followed by 24h in fresh medium +/- estradiol (E/sub 2/). The pituitary cells were then incubated in fresh medium containing radiolabeled precursors +/- gonadotropin releasing hormone (GnRH). Radioactive precursor incorporation into LH was determined by immuno-precipitation. The dose-dependent effects of E/sub 2/(10/sup -11/ to 10/sup -8/M) on /sup 3/H-glucosamine (/sup 3/H-Gln) and /sup 35/S-methionine (/sup 35/S-Met) incorporation into LH +/- 1 nM GnRH (4h) were investigated. GnRH (10/sup -9/M) and E/sub 2/ (all doses) significantly increased total /sup 3/H-Gln LH. Moreover, E/sub 2/ at 10/sup -9/M and 10/sup -8/M significantly enhanced GnRH stimulated LH glycosylation. In contrast, addition of GnRH and/or E/sub 2/ did not significantly increase /sup 35/S-Met incorporation into LH over a 4h period. The effects of various GnRH concentrations (10/sup -11/ to 10/sup -9/M; 8h) +/- E/sub 2/ (0.05 nM) on /sup 3/H-Gln LH and /sup 35/S-Met LH production were also investigated. In the absence of E/sub 2/, only 10/sup -9/M GnRH was effective in increasing total /sup 3/H-Gln LH and /sup 35/S-Met LH synthesis. However, in the presence of E/sub 2/, all concentrations of GnRH stimulated LH synthesis with /sup 3/H-Gln LH production responding in a dose related manner whereas /sup 35/S-Met LH production was maximally stimulated at all doses of GnRH. In the final series of experiments, pituitary cells previously exposed to estradiol were incubated for 4 h in normal calcium or low calcium medium containing /sup 3/H-Gln or /sup 35/S-Met +/- GnRH. Removal of extracellular calcium completely inhibited GnRH stimulated /sup 3/H-Gln LH and /sup 35/S-Met LH production.

  14. Expression and physiological regulation of BDNF receptors in the neuroendocrine melanotrope cell of Xenopus laevis

    NARCIS (Netherlands)

    Kidane, A.H.; Dooren, S.H. van; Roubos, E.W.; Jenks, B.G.

    2007-01-01

    Brain-derived neurotrophic factor (BDNF) and alpha-melanophore-stimulating hormone (alpha-MSH) are co-sequestered in secretory granules in melanotrope cells of the pituitary pars intermedia of the amphibian Xenopus laevis. alpha-MSH is responsible for pigment dispersion in dermal melanophores during

  15. Genomic profiling of a combined large cell neuroendocrine carcinoma of the submandibular gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Persson, Marta; Kiss, Katalin

    2016-01-01

    A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small-cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection...

  16. Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis.

    Science.gov (United States)

    Walter, Robert Fred Henry; Werner, Robert; Ting, Saskia; Vollbrecht, Claudia; Theegarten, Dirk; Christoph, Daniel Christian; Schmid, Kurt Werner; Wohlschlaeger, Jeremias; Mairinger, Fabian Dominik

    2015-09-22

    Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis. Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated. ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC. Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC. Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC.

  17. Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron.

    Science.gov (United States)

    Kirilov, Milen; Clarkson, Jenny; Liu, Xinhuai; Roa, Juan; Campos, Pauline; Porteous, Rob; Schütz, Günther; Herbison, Allan E

    2013-01-01

    Signaling between kisspeptin and its receptor, G-protein-coupled receptor 54 (Gpr54), is now recognized as being essential for normal fertility. However, the key cellular location of kisspeptin-Gpr54 signaling is unknown. Here we create a mouse with a GnRH neuron-specific deletion of Gpr54 to assess the role of gonadotropin-releasing hormone (GnRH) neurons. Mutant mice are infertile, fail to go through puberty and exhibit markedly reduced gonadal size and follicle-stimulating hormone levels alongside GnRH neurons that are unresponsive to kisspeptin. In an attempt to rescue the infertile phenotype of global Gpr54⁻/⁻ mutants, we use BAC transgenesis to target Gpr54 to the GnRH neurons. This results in mice with normal puberty onset, estrous cyclicity, fecundity and a recovery of kisspeptin's stimulatory action upon GnRH neurons. Using complimentary cell-specific knockout and knockin approaches we demonstrate here that the GnRH neuron is the key site of kisspeptin-Gpr54 signaling for fertility.

  18. Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells.

    Science.gov (United States)

    Feinshreiber, Lori; Singer-Lahat, Dafna; Friedrich, Reut; Matti, Ulf; Sheinin, Anton; Yizhar, Ofer; Nachman, Rachel; Chikvashvili, Dodo; Rettig, Jens; Ashery, Uri; Lotan, Ilana

    2010-06-01

    Regulation of exocytosis by voltage-gated K(+) channels has classically been viewed as inhibition mediated by K(+) fluxes. We recently identified a new role for Kv2.1 in facilitating vesicle release from neuroendocrine cells, which is independent of K(+) flux. Here, we show that Kv2.1-induced facilitation of release is not restricted to neuroendocrine cells, but also occurs in the somatic-vesicle release from dorsal-root-ganglion neurons and is mediated by direct association of Kv2.1 with syntaxin. We further show in adrenal chromaffin cells that facilitation induced by both wild-type and non-conducting mutant Kv2.1 channels in response to long stimulation persists during successive stimulation, and can be attributed to an increased number of exocytotic events and not to changes in single-spike kinetics. Moreover, rigorous analysis of the pools of released vesicles reveals that Kv2.1 enhances the rate of vesicle recruitment during stimulation with high Ca(2+), without affecting the size of the readily releasable vesicle pool. These findings place a voltage-gated K(+) channel among the syntaxin-binding proteins that directly regulate pre-fusion steps in exocytosis.

  19. Anti-Ri-associated paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis in a patient with mixed large cell neuroendocrine lung carcinoma.

    Science.gov (United States)

    Mitchell, Amber N; Bakhos, Charles T; Zimmerman, Earl A

    2015-02-01

    Paraneoplastic neurologic syndromes (PNS) can be the first manifestations of occult malignancies. If left untreated, PNS often lead to significant morbidity and mortality. Anti-Ri (anti-neuronal nuclear antibody type 2 [ANNA-2]) autoantibodies are commonly associated with breast and small cell lung cancers. Cases of anti-Ri paraneoplastic cerebellar degeneration are reported, but few describe severe nausea and coexisting limbic encephalitis as the major presenting features. We report a 75-year-old woman with medically-intractable emesis, encephalopathy, diplopia, vertigo, and gait ataxia for 3 months. Examination revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Anti-Ri antibodies were positive in serum only. CT scan identified a 2.0 cm left lung mass, and histopathology revealed large cell neuroendocrine carcinoma with admixed adenocarcinoma non-small cell lung carcinoma (NCSLC). Though the patient achieved nearly complete clinical recovery after tumor resection, anti-Ri levels remained high at 20 months post-resection. To our knowledge this is the first report of a paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis involving anti-Ri positivity and associated mixed neuroendocrine/NSCLC of the lung with marked improvement after tumor resection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Melatonin Inhibits GnRH-1, GnRH-3 and GnRH Receptor Expression in the Brain of the European Sea Bass, Dicentrarchus labrax

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    José Antonio Muñoz-Cueto

    2013-04-01

    Full Text Available Several evidences supported the existence of melatonin effects on reproductive system in fish. In order to investigate whether melatonin is involved in the modulation of GnRH systems in the European sea bass, we have injected melatonin (0.5 µg/g body mass in male specimens. The brain mRNA transcript levels of the three GnRH forms and the five GnRH receptors present in this species were determined by real time quantitative PCR. Our findings revealed day–night variations in the brain expression of GnRH-1, GnRH-3 and several GnRH receptors (dlGnRHR-II-1c, -2a, which exhibited higher transcript levels at mid-light compared to mid-dark phase of the photocycle. Moreover, an inhibitory effect of melatonin on the nocturnal expression of GnRH-1, GnRH-3, and GnRH receptors subtypes 1c, 2a and 2b was also demonstrated. Interestingly, the inhibitory effect of melatonin affected the expression of hypophysiotrophic GnRH forms and GnRH receptors that exhibit day–night fluctuations, suggesting that exogenous melatonin reinforce physiological mechanisms already established. These interactions between melatoninergic and GnRH systems could be mediating photoperiod effects on reproductive and other rhythmic physiological events in the European sea bass.

  1. High glucose induces N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 T-type calcium channels in neuroendocrine-like differentiated human prostate cancer cells.

    Science.gov (United States)

    Fukami, Kazuki; Asano, Erina; Ueda, Mai; Sekiguchi, Fumiko; Yoshida, Shigeru; Kawabata, Atsufumi

    2017-01-01

    Given that Cav3.2 T-type Ca(2+) channels were functionally regulated by asparagine (N)-linked glycosylation, we examined effects of high glucose on the function of Cav3.2, known to regulate secretory function, in neuroendocrine-like differentiated prostate cancer LNCaP cells. High glucose accelerated the increased channel function and overexpression of Cav3.2 during neuroendocrine differentiation, the former prevented by enzymatic inhibition of N-glycosylation and cleavage of N-glycans. Hyperglycemia thus appears to induce N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 in neuroendocrine-like differentiated prostate cancer cells. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  2. High glucose induces N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 T-type calcium channels in neuroendocrine-like differentiated human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Kazuki Fukami

    2017-01-01

    Full Text Available Given that Cav3.2 T-type Ca2+ channels were functionally regulated by asparagine (N-linked glycosylation, we examined effects of high glucose on the function of Cav3.2, known to regulate secretory function, in neuroendocrine-like differentiated prostate cancer LNCaP cells. High glucose accelerated the increased channel function and overexpression of Cav3.2 during neuroendocrine differentiation, the former prevented by enzymatic inhibition of N-glycosylation and cleavage of N-glycans. Hyperglycemia thus appears to induce N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 in neuroendocrine-like differentiated prostate cancer cells.

  3. Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

    Directory of Open Access Journals (Sweden)

    Guo S

    2017-03-01

    size was increased (10±0.28 vs 7±0.28; P<0.05 after GnRH agonist treatment. Three hundred and fifty-nine genes were differentially expressed in the GnRH agonist-treated group compared with the untreated group (218 were downregulated and 141 were upregulated. Differentially expressed genes were related to diverse biological processes, including estrogen metabolism, cell cycle, and metabolite biosynthesis.Conclusion: GnRH agonist treatment appears to improve the pregnancy outcome of adenomyosis in a mouse model. Besides pituitary down-regulation, other possible mechanisms such as the regulation of cell proliferation may play a role in this. These new insights into GnRH agonist mechanisms will be useful for future adenomyosis treatment. Keywords: adenomyosis, GnRH agonist, mouse, RNA-seq, pregnancy outcome

  4. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

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    Freddyson J Martínez-Rivera

    Full Text Available The abuse of anabolic androgenic steroids (AAS has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH. In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM. These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

  5. The Interrelationship of Estrogen Receptor and GnRH in a Basal Vertebrate, the Sea Lamprey

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    Stacia A Sower

    2011-10-01

    Full Text Available The hypothalamic-pituitary system is considered to be a vertebrate innovation and seminal event that emerged prior to or during the differentiation of the ancestral agnathans. Lampreys are the earliest evolved vertebrates for which there is a demonstrated neuroendocrine system. Lampreys have three hypothalamic GnRHs (lGnRH-I, -II, and –III and two and possibly three pituitary GnRH receptors involved in mediating reproductive processes. Estradiol is considered to be a major reproductive steroid in both male and female lampreys. The purpose of this study was to investigate estrogen receptor (ER expression in the lamprey brain in adult sea lampreys. Expression of ER mRNA was confirmed in the adult lamprey brain using RT-PCR. Using digoxigenin (DIG-labeled probes, ER expression was shown to yield moderate, but distinct reaction products in specific neuronal nuclei of the lamprey brain, including the olfactory lobe, hypothalamus, habenular area, and hindbrain. Expression of ER in the hypothalamic area of the brain provides evidence of potential interaction between estradiol and GnRH(s, and is consistent with previous evidence showing estrogen feedback on GnRH in adult lamprey brain. Earlier studies have reported that there is a close distribution of GAD (GABA and lamprey GnRH in the preoptic region in adult lampreys. The establishment of a direct estradiol-kisspeptin-GABA-GnRH interaction in lamprey has yet to be determined and will require future functional and co-localization studies. The phylogenetic position of lampreys as a basal vertebrate allows lampreys to be a basis for understanding the molecular evolution of the neuroendocrine system that arose in the vertebrates.

  6. Molecular analysis of the koala reproductive hormones and their receptors: gonadotrophin-releasing hormone (GnRH), follicle-stimulating hormone β and luteinising hormone β with localisation of GnRH.

    Science.gov (United States)

    Busby, E R; Soeta, S; Sherwood, N M; Johnston, S D

    2014-12-01

    During evolution, reproductive hormones and their receptors in the brain-pituitary-gonadal axis have been altered by genetic mechanisms. To understand how the neuroendocrine control of reproduction evolved in mammals, it is important to examine marsupials, the closest group to placental mammals. We hypothesised that at least some of the hormones and receptors found in placental mammals would be present in koala, a marsupial. We examined the expression of koala mRNA for the reproductive molecules. Koala cDNAs were cloned from brain for gonadotrophin-releasing hormones (GnRH1 and GnRH2) or from pituitary for GnRH receptors, types I and II, follicle-stimulating hormone (FSH)β and luteinising hormone (LH)β, and from gonads for FSH and LH receptors. Deduced proteins were compared by sequence alignment and phylogenetic analysis with those of other vertebrates. In conclusion, the koala expressed mRNA for these eight putative reproductive molecules, whereas at least one of these molecules is missing in some species in the amniote lineage, including humans. In addition, GnRH1 and 2 are shown by immunohistochemistry to be expressed as proteins in the brain. © 2014 British Society for Neuroendocrinology.

  7. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...... of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs...

  8. GnRH neurons on LSD: a year of rejecting hypotheses that may have made Karl Popper proud.

    Science.gov (United States)

    Moenter, Suzanne M

    2017-11-08

    Gonadotropin-releasing hormone (GnRH) neurons are critical to many aspects of fertility regulation, from producing episodic release critical to both sexes, to providing a central signal to induce the ovulatory cascade in females. This year saw progress through the rejection, and occasional support, of hypotheses in understanding how GnRH neurons contribute to these processes. This brief review provides one laboratory's view of new insights into possible roles for these cells in development, adult reproductive function, and what may go wrong with GnRH neurons in some cases of infertility. Copyright © 2017 Endocrine Society.

  9. The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.

    Directory of Open Access Journals (Sweden)

    Svenja Nölting

    Full Text Available The therapeutic options for metastatic neuroendocrine tumors (NETs are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1 and pulmonary (H727 NET cell lines.Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA.BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately.Our results suggest that the agent BYL719 could be a novel therapeutic approach to the

  10. A short history of neuroendocrine tumours and their peptide hormones

    DEFF Research Database (Denmark)

    de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark

    2016-01-01

    The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The panc...

  11. Neuroendocrine Merkel cell carcinoma is associated with mutations in key DNA repair, epigenetic and apoptosis pathways: a case-based study using targeted massively parallel sequencing.

    Science.gov (United States)

    Graves, Christian A; Jones, Ashley; Reynolds, Justin; Stuart, Jeremy; Pirisi, Lucia; Botrous, Peter; Wells, James

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma with a poorly understood molecular etiology. We implemented a comprehensive deep sequencing approach to identify mutations in the tumor DNA from a cohort of patients treated at our institution over the past 15 years. Our results indicate mutations that may constitute therapeutic targets in MCC. Five patients were treated for MCC within the study interval. Patients with adequate tissue (n = 4), positive neuroendocrine differentiation (chromogranin, synaptophysin, and cytokeratin 20), and histopathological confirmation of MCC were included in the study. DNA was extracted from archival tumor tissue samples and analyzed by massively parallel sequencing using a targeted, multiplex PCR approach followed by semiconductor sequencing. We demonstrate high-penetrance nonsense mutations in PDE4DIP (n = 4) as well as various missense mutations in the DNA damage response (PRKDC, AURKB, ERCC5, ATR, and ATRX) and epigenetic modulating enzymes (MLL3). We describe several mutations in potential disease-relevant genes and pathways. These targets should be evaluated in a larger cohort to determine their role in the molecular pathogenesis of MCC. © 2015 S. Karger AG, Basel.

  12. PET/CT in Neuroendocrine Tumors.

    Science.gov (United States)

    Castellucci, Paolo; Ambrosini, Valentina; Montini, Giancarlo

    2008-04-01

    Neuroendocrine tumors (NETs) are a rare group of neoplasms that originate from pluripotent stem cells or differentiated neuroendocrine cells, mostly localized in the bronchus, lungs, or gastroenteropancreatic tract. This issue reviews the results achieved with PET. The potential applications of the most commonly used receptor or metabolic positron-emitter radiopharmaceuticals in the field of NET to stage or restage disease, to detect unknown primary tumor, and to assess and monitor therapy response to different kind of treatments are analyzed. Copyright © 2008 Elsevier Inc. All rights reserved.

  13. Neuroendocrine differentiation in prostate cancer – a review

    Directory of Open Access Journals (Sweden)

    R. Popescu

    2015-12-01

    Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

  14. Gonadotropin-Releasing Hormone (GnRH) Receptor Structure and GnRH Binding.

    Science.gov (United States)

    Flanagan, Colleen A; Manilall, Ashmeetha

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) regulates reproduction. The human GnRH receptor lacks a cytoplasmic carboxy-terminal tail but has amino acid sequence motifs characteristic of rhodopsin-like, class A, G protein-coupled receptors (GPCRs). This review will consider how recent descriptions of X-ray crystallographic structures of GPCRs in inactive and active conformations may contribute to understanding GnRH receptor structure, mechanism of activation and ligand binding. The structures confirmed that ligands bind to variable extracellular surfaces, whereas the seven membrane-spanning α-helices convey the activation signal to the cytoplasmic receptor surface, which binds and activates heterotrimeric G proteins. Forty non-covalent interactions that bridge topologically equivalent residues in different transmembrane (TM) helices are conserved in class A GPCR structures, regardless of activation state. Conformation-independent interhelical contacts account for a conserved receptor protein structure and their importance in the GnRH receptor structure is supported by decreased expression of receptors with mutations of residues in the network. Many of the GnRH receptor mutations associated with congenital hypogonadotropic hypogonadism, including the Glu2.53(90) Lys mutation, involve amino acids that constitute the conserved network. Half of the ~250 intramolecular interactions in GPCRs differ between inactive and active structures. Conformation-specific interhelical contacts depend on amino acids changing partners during activation. Conserved inactive conformation-specific contacts prevent receptor activation by stabilizing proximity of TM helices 3 and 6 and a closed G protein-binding site. Mutations of GnRH receptor residues involved in these interactions, such as Arg3.50(139) of the DRY/S motif or Tyr7.53(323) of the N/DPxxY motif, increase or decrease receptor expression and efficiency of receptor coupling to G protein signaling, consistent with the native residues

  15. Synchronous Quadruple Primary Neoplasms: Colon Adenocarcinoma, Collision Tumor of Neuroendocrine Tumor and Schwann Cell Hamartoma and Sessile Serrated Adenoma of the Appendix.

    Science.gov (United States)

    Meeks, Marshall W; Grace, Shane; Chen, Yongxin; Petterchak, James; Bolesta, Edward; Zhou, Yihua; Lai, Jin-Ping

    2016-08-01

    Quadruple synchronous primary neoplasms are very rare with only three cases reported in the English-speaking literature to date. Collision tumors are also rare entities, especially of the appendix. We herein report a case of synchronous quadruple primary neoplasm in a 95-year-old female. She was diagnosed with colon adenocarcinoma, sessile serrated adenoma of the appendix and a collision tumor composed of a well-differentiated neuroendocrine tumor and Schwann cell hamartoma. Histological examination and immunohistochemistry supported these four lesions as separate entities. This case is unique because we report the diagnosis of quadruple synchronous primary, an extremely rare occurrence, in addition to a collision tumor of the appendix. We also provide a review of the literature for synchronous neoplasms and collision tumors. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. ERCC1 and Ki67 in Small Cell Lung Carcinoma and Other Neuroendocrine Tumors of the Lung Distribution and Impact on Survival

    DEFF Research Database (Denmark)

    Skov, Birgit Guldhammer; Holm, B.; Erreboe, A.

    2010-01-01

    ), typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LCNEC) were determined. Materials and Methods: We included a consecutive series of 186 patients with SCLC treated with platinum-based chemotherapy and surgically treated patients with TC (n = 48), AC (n = 15......) and LCNEC (n = 27). ERCC1 and Ki 67 were measured by immunohistochemistry and scored using published criteria. Results: The expression of ERCC1 was different among the different tumor types (p disease as well as extensive disease SCLC, no association of ERCC1 expression.......001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC + AC) and high grade NE (LCNEC + SCLC) (p treated...

  17. in seasonally anoestms GnRH-

    African Journals Online (AJOL)

    luteotrophic effect of progestogen priming followed by a multi- ple injection regime of GnRH. The life-span of corpora lutea induced by HCG was prolonged during postpartum anoestrus in cows pretreated with progesterone implants, but not in cows primed with oestradiol (pratt, Berardinelli, Stevens & Inskeep,. 1982).

  18. Differential fibroblast growth factor 8 (FGF8-mediated autoregulation of its cognate receptors, Fgfr1 and Fgfr3, in neuronal cell lines.

    Directory of Open Access Journals (Sweden)

    Natasha N Mott

    2010-04-01

    Full Text Available Fibroblast growth factors (FGFs mediate a vast range of CNS developmental processes including neural induction, proliferation, migration, and cell survival. Despite the critical role of FGF signaling for normal CNS development, few reports describe the mechanisms that regulate FGF receptor gene expression in the brain. We tested whether FGF8 could autoregulate two of its cognate receptors, Fgfr1 and Fgfr3, in three murine cell lines with different lineages: fibroblast-derived cells (3T3 cells, neuronal cells derived from hippocampus (HT-22 cells, and neuroendocrine cells derived from hypothalamic gonadotropin-releasing hormone (GnRH neurons (GT1-7 cells. GnRH is produced by neurons in the hypothalamus and is absolutely required for reproductive competence in vertebrate animals. Several lines of evidence strongly suggest that Fgf8 is critical for normal development of the GnRH system, therefore, the GT1-7 cells provided us with an additional endpoint, Gnrh gene expression and promoter activity, to assess potential downstream consequences of FGF8-induced modulation of FGF receptor levels. Results from this study suggest that the autoregulation of its cognate receptor represents a common downstream effect of FGF8. Further, we show that Fgfr1 and Fgfr3 are differentially regulated within the same cell type, implicating these two receptors in different biological roles. Moreover, Fgfr1 and Fgfr3 are differentially regulated among different cell types, suggesting such autoregulation occurs in a cell type-specific fashion. Lastly, we demonstrate that FGF8b decreases Gnrh promoter activity and gene expression, possibly reflecting a downstream consequence of altered FGF receptor populations. Together, our data bring forth the possibility that, in addition to the FGF synexpression group, autoregulation of FGFR expression by FGF8 represents a mechanism by which FGF8 could fine-tune its regulatory actions.

  19. The forebrain-midbrain acts as functional endocrine signaling pathway of Kiss2/Gnrh1 system controlling the gonadotroph activity in the teleost fish European sea bass (Dicentrarchus labrax).

    Science.gov (United States)

    Espigares, Felipe; Carrillo, Manuel; Gómez, Ana; Zanuy, Silvia

    2015-03-01

    Some teleost species, including European sea bass, harbor two different kisspeptin coding genes: kiss1 and kiss2. Both genes are expressed in the brain, but their differential roles in the central control of fish reproduction are only beginning to be elucidated. In this study, we have examined the effects of intracerebroventricular injections of the highly active sea bass peptides Kiss1-15 and Kiss2-12 on spermiating male sea bass. Physiological saline, Kiss1-15, or Kiss2-12 was injected into the third ventricle. To establish the gene expression cascade involved in the action of kisspeptins, the expression of the two sea bass kisspeptin receptor genes (kiss1r and kiss2r) and the three sea bass Gnrh genes (gnrh1, gnrh2, and gnrh3) were analyzed in the forebrain-midbrain and the hypothalamus. In addition, the protein levels of hypothalamic and pituitary Gnrh1 were measured. Blood samples were collected at different times after injection to analyze the effects of kisspeptins on the release of gonadotropins (Lh and Fsh) and androgens (testosterone and 11-ketotestosterone). The present results provide the first evidence that the effects of Kiss2 on central regulation of reproductive function involve the neuroendocrine areas of the forebrain-midbrain in teleost fish. The marked effect of Kiss2 on kiss2r and gnrh1 expression in the forebrain-midbrain and on Gnrh1 release suggest that this neuronal system is involved in the neuroendocrine regulation of gonadotroph activity. This hypothesis was confirmed by a surge of plasma Lh in response to Kiss2, which presumably has a strong stimulatory effect on testosterone release, and thus on sperm quality parameters. © 2015 by the Society for the Study of Reproduction, Inc.

  20. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  1. Nuclear Image Analysis Study of Neuroendocrine Tumors

    OpenAIRE

    Park, Meeja; Baek, Taehwa; Baek, Jongho; Son, Hyunjin; Kang, Dongwook; Kim, Jooheon; Lee, Hyekyung

    2012-01-01

    Background There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images. Methods We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells a...

  2. EGF Prevents the Neuroendocrine Differentiation of LNCaP Cells Induced By Serum Deprivation: The Modulator Role of P13K/Akt

    Directory of Open Access Journals (Sweden)

    Rosa M. Martín-Orozco

    2007-08-01

    Full Text Available The primary focus of this investigation was to study the relationship between neuroendocrine (NE differentiation, epidermal growth factor (EGF because both have been implicated in the progression of prostate cancer. For this purpose, we used gefitinib, trastuzumab, which are inhibitors of EGF receptor (EGFR, ErbB2, respectively. EGF prevents NE differentiation induced by androgen depletion. This effect is prevented by gefitinib, which blocks the activation of EGFR, ErbB2, stimulation of mitogen-activated protein kinase (MAPK, cell proliferation induced by EGF. Conversely, trastuzumab does not inhibit the effect of EGF on EGFR phosphorylation, MAPK activity, cell proliferation, NE differentiation, although it reduces ErbB2 levels specifically, suggesting that ErbB2 is not necessary to inhibit NE differentiation. Prevention of NE differentiation by EGF is mediated by a MAPK-dependent mechanism, requires constitutive Akt activation. The abrogation of the PI3K/Akt pathway changes the role of EGF from inhibitor to inductor of NE differentiation. We show that EGFR tyrosine kinase, MAPK, PI3K inhibitors inhibit the cell proliferation stimulated by EGF but induce the acquisition of NE phenotype. Altogether, the present data should be borne in mind when designing new clinical schedules for the treatment of prostate cancer, including the use of ErbB receptors, associated signaling pathway inhibitors.

  3. Small cell neuroendocrine carcinoma of the endometrium with pulmonary metastasis: A clinicopathologic study of a case and a brief review of the literature

    Directory of Open Access Journals (Sweden)

    Antonio D'Antonio

    2016-02-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and rare tumors that usually involve the cervix and ovary, and are seen rarely in the endometrium in perimenopausal or postmenopausal women. We presented a case of a73 year-old postmenopausal woman with vaginal bleeding and abdominal pain. A subsequent computerized tomography (CT scan of pelvis showed an enlarged uterus (20,0 × 12,0 cm with para-aortic and pelvic lymph node metastases. She underwent surgical debulking and staging of an endometrial tumor with omental metastasis and positive lymph nodes. The pathological diagnosis was primary small cell carcinoma (SCC combined with endometrioid carcinoma of uterine corpus. Her final FIGO stage was IVB. Three months after surgery CT-total body showed a metastasis to left lung of SCC. Because the small-cell component of endometrial tumor showed a strong positivity for TTF1 as pulmonary counterpart a differential diagnosis with a primary small cell carcinoma of the lung should be made. Identifying an appropriate therapeutic management for SCC of endometrium is challenging since these are extremely rare tumors. An optimal initial therapeutic approach to this rare disease, especially at an advanced stage, has not yet been clearly defined. However, in these a multidisciplinary therapy, including surgery, chemotherapy, and radiotherapy represent until this time the only therapeutic option.

  4. Benign gastric neuroendocrine tumors in three snow leopards (Panthera uncia).

    Science.gov (United States)

    Dobson, Elizabeth C; Naydan, Dianne K; Raphael, Bonnie L; McAloose, Denise

    2013-06-01

    Neuroendocrine tumors are relatively rare neoplasms arising from neuroendocrine cells that are distributed throughout the body and are predominant in the gastrointestinal tract. This report describes benign, well-differentiated gastric neuroendocrine tumors in three captive snow leopards (Panthera uncia). All tumors were well circumscribed, were within the gastric mucosa or submucosa, and had histologic and immunohistochemical features of neuroendocrine tumors. Histologic features included packeted cuboidal to columnar epithelial cells that were arranged in palisades or pseudorosettes and contained finely granular cellular cytoplasm with centrally placed, round nuclei. Cytoplasmic granules of neoplastic cells strongly expressed chromogranin A, variably expressed neuron-specific enolase, and did not express synaptophysin or gastrin. Each leopard died or was euthanatized for reasons unrelated to its tumor.

  5. Primary neuroendocrine carcinoma of the breast: report of 2 cases and literature review

    Directory of Open Access Journals (Sweden)

    Fernando Collado-Mesa, MD

    2017-03-01

    Full Text Available Neuroendocrine tumors of the breast are very rare accounting for less than 0.1% of all breast cancers and less than 1% of all neuroendocrine tumors. Focal neuroendocrine differentiation can be found in different histologic types of breast carcinoma including in situ and invasive ductal or invasive lobular. However, primary neuroendocrine carcinoma of the breast requires the expression of neuroendocrine markers in more than 50% of the cell population, the presence of ductal carcinoma in situ, and the absence of clinical evidence of concurrent primary neuroendocrine carcinoma of any other organ. Reports discussing the imaging characteristics of this rare carcinoma in different breast imaging modalities are scarce. We present 2 cases of primary neuroendocrine carcinoma of the breast for which mammography, ultrasound, and magnetic resonance imaging findings and pathology findings are described. A review of the medical literature on this particular topic was performed, and the results are presented.

  6. Mixed adenocarcinoma and neuroendocrine prostate cancer: a case report

    Directory of Open Access Journals (Sweden)

    Rittu Hingorani

    2014-11-01

    Full Text Available Background: Neuroendocrine prostate cancer is rare but lethal. It is one of the most common extra pulmonary manifestations of small cell cancer. Case presentation: Here we present a case report of a 53-year-old male who presents with a mixed adenocarcinoma and neuroendocrine prostate tumor on a background of previously normal prostate-specific antigen (PSA. His initial symptoms prior to diagnosis included decreased urine output and acute kidney injury (AKI. Conclusion: Neuroendocrine tumor does not elevate the PSA level and hence is often a late finding with a poor prognosis. Special staining on histopathogy is required to reveal this diagnosis.

  7. In silico and in situ characterization of the zebrafish (Danio rerio gnrh3 (sGnRH gene

    Directory of Open Access Journals (Sweden)

    Husebye Harald

    2002-08-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GnRH is responsible for stimulation of gonadotropic hormone (GtH in the hypothalamus-pituitary-gonadal axis (HPG. The regulatory mechanisms responsible for brain specificity make the promoter attractive for in silico analysis and reporter gene studies in zebrafish (Danio rerio. Results We have characterized a zebrafish [Trp7, Leu8] or salmon (s GnRH variant, gnrh3. The gene includes a 1.6 Kb upstream regulatory region and displays the conserved structure of 4 exons and 3 introns, as seen in other species. An in silico defined enhancer at -976 in the zebrafish promoter, containing adjacent binding sites for Oct-1, CREB and Sp1, was predicted in 2 mammalian and 5 teleost GnRH promoters. Reporter gene studies confirmed the importance of this enhancer for cell specific expression in zebrafish. Interestingly the promoter of human GnRH-I, known as mammalian GnRH (mGnRH, was shown capable of driving cell specific reporter gene expression in transgenic zebrafish. Conclusions The characterized zebrafish Gnrh3 decapeptide exhibits complete homology to the Atlantic salmon (Salmo salar GnRH-III variant. In silico analysis of mammalian and teleost GnRH promoters revealed a conserved enhancer possessing binding sites for Oct-1, CREB and Sp1. Transgenic and transient reporter gene expression in zebrafish larvae, confirmed the importance of the in silico defined zebrafish enhancer at -976. The capability of the human GnRH-I promoter of directing cell specific reporter gene expression in zebrafish supports orthology between GnRH-I and GnRH-III.

  8. Development of the Neuroendocrine Hypothalamus.

    Science.gov (United States)

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-03-15

    The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity. Copyright © 2016 John Wiley & Sons, Inc.

  9. Perinatal exposure to organohalogen pollutants decreases vasopressin content and its mRNA expression in magnocellular neuroendocrine cells activated by osmotic stress in adult rats

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported t...

  10. Neuroendocrine tumors in the urinary bladder: a literature review

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    Monika Ulamec

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs can be found in most organs, as well as in the urinary bladder. Some of the clinical and pathologic features of these tumors may be characteristic of the organ of origin, but most of the properties are shared by neuroendocrine neoplasms regardless of their anatomic site. In the bladder, NETs comprise less than 1% of all bladder tumors and can be found in a pure form or intermixed with urothelial carcinoma and its variants. Bladder NETs are classified into 2 subtypes: carcinoid tumor and neuroendocrine carcinoma, which is further subdivided into small cell and large cell neuroendocrine carcinoma. Characteristics of bladder NETs and its differential diagnosis are discussed herein.

  11. Social Crowding during Development Causes Changes in GnRH1 DNA Methylation.

    Science.gov (United States)

    Alvarado, Sebastian G; Lenkov, Kapa; Williams, Blake; Fernald, Russell D

    2015-01-01

    Gestational and developmental cues have important consequences for long-term health, behavior and adaptation to the environment. In addition, social stressors cause plastic molecular changes in the brain that underlie unique behavioral phenotypes that also modulate fitness. In the adult African cichlid, Astatotilapia burtoni, growth and social status of males are both directly regulated by social interactions in a dynamic social environment, which causes a suite of plastic changes in circuits, cells and gene transcription in the brain. We hypothesized that a possible mechanism underlying some molecular changes might be DNA methylation, a reversible modification made to cytosine nucleotides that is known to regulate gene function. Here we asked whether changes in DNA methylation of the GnRH1 gene, the central regulator of the reproductive axis, were altered during development of A. burtoni. We measured changes in methylation state of the GnRH1 gene during normal development and following the gestational and developmental stress of social crowding. We found differential DNA methylation within developing juveniles between 14-, 28- and 42-day-old. Following gestational crowding of mouth brooding mothers, we saw differential methylation and transcription of GnRH1 in their offspring. Taken together, our data provides evidence for social control of GnRH1 developmental responses to gestational cues through DNA methylation.

  12. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release.

    Science.gov (United States)

    Ansel, L; Bentsen, A H; Ancel, C; Bolborea, M; Klosen, P; Mikkelsen, J D; Simonneaux, V

    2011-09-01

    In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase in circulating testosterone. The activation of pituitary cells by Kp was inhibited by preadministration of the GNRH receptor antagonist acyline. Altogether, our results demonstrate that peripheral Kp54 activates the gonadotropic axis by stimulating GNRH release and indicate that an appropriate protocol of long-term systemic Kp administration can recrudesce a photo-inhibited reproductive axis.

  13. Large cell neuroendocrine carcinoma originating from the uterine endometrium: a report on magnetic resonance features of 2 cases with very rare and aggressive tumor

    Directory of Open Access Journals (Sweden)

    Natsuko Makihara

    2012-06-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.

  14. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity

    Science.gov (United States)

    Geenen, Vincent; Bodart, Gwennaëlle; Henry, Séverine; Michaux, Hélène; Dardenne, Olivier; Charlet-Renard, Chantal; Martens, Henri; Hober, Didier

    2013-01-01

    For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of “neuroendocrine self-peptides” has been proposed, together with the definition of “neuroendocrine self.” Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). At the same time, self-antigen presentation in the thymus generates regulatory T (Treg) cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic

  15. Chloride Accumulators NKCC1 and AE2 in Mouse GnRH Neurons: Implications for GABAA Mediated Excitation.

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    Carol Taylor-Burds

    Full Text Available A developmental "switch" in chloride transporters occurs in most neurons resulting in GABAA mediated hyperpolarization in the adult. However, several neuronal cell subtypes maintain primarily depolarizing responses to GABAA receptor activation. Among this group are gonadotropin-releasing hormone-1 (GnRH neurons, which control puberty and reproduction. NKCC1 is the primary chloride accumulator in neurons, expressed at high levels early in development and contributes to depolarization after GABAA receptor activation. In contrast, KCC2 is the primary chloride extruder in neurons, expressed at high levels in the adult and contributes to hyperpolarization after GABAA receptor activation. Anion exchangers (AEs are also potential modulators of responses to GABAA activation since they accumulate chloride and extrude bicarbonate. To evaluate the mechanism(s underlying GABAA mediated depolarization, GnRH neurons were analyzed for 1 expression of chloride transporters and AEs in embryonic, pre-pubertal, and adult mice 2 responses to GABAA receptor activation in NKCC1-/- mice and 3 function of AEs in these responses. At all ages, GnRH neurons were immunopositive for NKCC1 and AE2 but not KCC2 or AE3. Using explants, calcium imaging and gramicidin perforated patch clamp techniques we found that GnRH neurons from NKCC1-/- mice retained relatively normal responses to the GABAA agonist muscimol. However, acute pharmacological inhibition of NKCC1 with bumetanide eliminated the depolarization/calcium response to muscimol in 40% of GnRH neurons from WT mice. In the remaining GnRH neurons, HCO3- mediated mechanisms accounted for the remaining calcium responses to muscimol. Collectively these data reveal mechanisms responsible for maintaining depolarizing GABAA mediated transmission in GnRH neurons.

  16. [The role of endoscopy in gastroenteropancreatic neuroendocrine tumors].

    Science.gov (United States)

    Magno, L; Sivero, L; Napolitano, V; Ruggiero, S; Fontanarosa, G; Massa, S

    2010-01-01

    Versione italiana Riassunto: Il ruolo dell'endoscopia nei tumori neuroendocrini gastroenteropancreatici. L. Magno, L. Sivero, V. Napolitano, S. Ruggiero, G. Fontanarosa, S. Massa I tumori neuroendocrini (NET) gastro-entero-pancreatici (GEP) sono neoplasie rare che originano dalle cellule neuroendocrine del tubo digerente e del pancreas. L'endoscopia digestiva e l'ecoendoscopia rivestono un ruolo importante nella diagnosi, stadiazione e sorveglianza dei pazienti con NET. Inoltre, in casi selezionati, le tecniche endoscopiche operative consentono il trattamento di queste neoplasie in fase precoce. English version Summary: The role of endoscopy in gastroenteropancreatic neuroendocrine tumors. L. Magno, L. Sivero, V. Napolitano, S. Ruggiero, G. Fontanarosa, S. Massa Gastroenteropancreatic (GEP) neuroendocrine tumors (NET) are rare neoplasia arisen from neuroendocrine cells present in the gut mucosa and pancreas. Digestive endoscopy and endoscopic ultrasonography play a relevant role in NET diagnosis, stadiation and surveillance. Moreover, in selected patients, surgical endoscopy allows the tratment of these cancers at an early stage.

  17. Taurine, energy drinks, and neuroendocrine effects.

    Science.gov (United States)

    Caine, Jonathan J; Geracioti, Thomas D

    2016-12-01

    Taurine is an amino acid found abundantly in brain, retina, heart, and reproductive organ cells, as well as in meat and seafood. But it is also a major ingredient in popular "energy drinks," which thus constitute a major source of taurine supplementation. Unfortunately, little is known about taurine's neuroendocrine effects. The authors review the sparse data and provide a basic background on the structure, synthesis, distribution, metabolism, mechanisms, effects, safety, and currently proposed therapeutic targets of taurine. Copyright © 2016 Cleveland Clinic.

  18. Acute Disseminated Intravascular Coagulation in Neuroendocrine Carcinoma

    OpenAIRE

    Ru-Wen Teh; Tsoi, Daphne T.

    2012-01-01

    Malignancy is a common cause of disseminated intravascular coagulation and usually presents as a chronic disorder in solid organ tumours. We present a rare case of recurrent acute disseminated intravascular coagulation in neuroendocrine carcinoma after manipulation, firstly, by core biopsy and, later, by cytotoxic therapy causing a release of procoagulants and cytokines from lysed tumour cells. This is reminiscent of tumour lysis syndrome where massive quantities of intracellular electrolytes...

  19. Neuroendocrine carcinoma of the prostate gland.

    Science.gov (United States)

    Hoof, Pamela; Tsai-Nguyen, Ginger; Paulson, Scott; Syed, Almas; Mora, Adam

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease.

  20. Optimisation of GnRH antagonist use in ART

    NARCIS (Netherlands)

    Hamdine, O.

    2014-01-01

    This thesis focuses on the optimisation of controlled ovarian stimulation for IVF using exogenous FSH and GnRH antagonist co-treatment, by studying the timing of the initiation of GnRH antagonist co-medication and the role of ovarian reserve markers in optimising ovarian response and reproductive

  1. GnRH injection before artificial insemination (AI) alters follicle ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... control group of Animals no injection of GnRH was performed. GnRH administered (Gonadorelin, 5 ml, intramuscular, made by. Aburaihan company, Tehran, Iran) on Day 6 of the estrous cycle. (estrus = Day 0). Ultrasonography examination. Ovarian follicular development was monitored daily by transrectal.

  2. High grade neuroendocrine neoplasm of the antrum and orbit.

    Science.gov (United States)

    MacIntosh, Peter W; Jakobiec, Frederick A; Stagner, Anna M; Gilani, Sapideh; Fay, Aaron

    2015-01-01

    Neuroendocrine malignancies-tumors characterized by the production of dense-core secretory granules-are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient's tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV-hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons

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    Tomoko eSoga

    2016-03-01

    Full Text Available Kisspeptin, a newly discovered neuropeptide regulates gonadotropin-releasing hormone (GnRH. Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by kiss1 gene is a 145-amino acid- protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein coupled receptor 54 (GPR54 has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP labelled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP–GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1nM treatment for 36h on GnRH migration. Furthermore to determine kisspeptin-induced molecular pathways related with apoptosis, and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser captured EGFP–GnRH neurons by real time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd 26 in EGFP–GnRH neurons was up-regulated by the exposure to kisspeptin. These studies suggest that ankrd26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin-GPR54 signaling, which could be a potential pathway to suppress cell migration.

  4. Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons

    Science.gov (United States)

    Soga, Tomoko; Lim, Wei Ling; Khoo, Alan Soo-Beng; Parhar, Ishwar S.

    2016-01-01

    Kisspeptin, a newly discovered neuropeptide, regulates gonadotropin-releasing hormone (GnRH). Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by KiSS-1 gene is a 145-amino acid protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein-coupled receptor 54 (GPR54) has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP) labeled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP–GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1 nM) treatment for 36 h on GnRH migration. Furthermore, to determine kisspeptin-induced molecular pathways related with apoptosis and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser-captured EGFP–GnRH neurons by real-time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd) 26 in EGFP–GnRH neurons was upregulated by the exposure to kisspeptin. These studies suggest that ankrd 26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin–GPR54 signaling, which could be a potential pathway to suppress cell migration. PMID:26973595

  5. GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET

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    Depalo Raffaella

    2012-04-01

    Full Text Available Abstract Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

  6. Neuroendocrine Carcinoma: Immunohistochemistry Department Of Cancer Institute 1996 - 2000

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    Yazdani F

    2003-07-01

    Full Text Available Dispersed neuroendocrine system (D.N.S consists of a wide variety of cells that are present in the central and peripheral nervous system and in many classic endocrine organs and different tissues such as respiratory and gastrointestinal tracts, skin, prostate, breast and also their neoplasm show neuroendocrine differentiation by electron microscopy, immunohistochemistry or biochemical techniques:"nMaterials and Methods: The present study has been carried out by case-series method in order to evaluating the characteristics of all types of neuroendocrine carcinoma: different anatomical locations during 5 years period in immunohistochemistry department of cancer institute."nResults: The diagnosis of 109 cases of neuroendocrine carcinoma consisting of neuroendocrine carcinoma, small cell carcinoma, medullary carcinoma of thyroid, carcinoid tumor and merkel cell carcinoma are confirmed that among them the most common diagnosis was related to neuroendocrine carcinoma (50.5 percent. The most prevalent age group was 40-49 years and male to female distribution were 56 percent and 44 percent respectively. Anatomical distribution of tumor show that about 30 percent of cases were metastatic carcinoma, 30 percent in thyroid, respiratory tract and head and neck region and remainder in a variety of tissues. In over 50 percent of cases one of endocrinoid patterns as trabecular, organoid or mixed of them were seen."nConclusion: Immunohistochemically N.S.E (Neuron Specific Enolase show high sensitivity with 96 percent positive reaction and more specific endocrine markers as chromogranin A in 80 percent and synaptophysin only in 24 percent because of lesser application of the latter. Also epithelial markers such as cytokeratin and E.M.A."n(Epithelial Membrane Antigen were positive in 69 percent and 74 percent respectively. Mean survival rate of all neuroendocrine carcinoma reached to 4.8 years with lowest survival of 4.3 years among small cell carcinoma and

  7. Photoaffinity labeling of pituitary GnRH receptors: significance of the position of photolabel on the ligand

    Energy Technology Data Exchange (ETDEWEB)

    Nikolics, K.; Szonyi, E.; Ramachandran, J.

    1988-03-08

    Photoreactive derivatives of GnRH and its analogues were prepared by incorporation of the 2-nitro-4(5)-azidophenylsulfenyl (2,4(5)-NAPS) group into amino acid residues at position 1, 3, 6, or 8 of the decapeptide sequence. The modification of Trp/sup 3/ by the 2,4-NAPS group led to a complete loss of the luteinizing hormone (LH) releasing as well as LH-release-inhibiting activity of the peptide. The (D-Lys(2,4-NAPS))/sup 6/ analog was a very potent agonist that, after covalent attachment by photoaffinity labeling, caused prolonged LH secretion at a submaximal rate. (Orn(2,4-NAPS))/sup 8/-GnRH, a full agonist with a relative potency of 7% of GnRH, after photoaffinity labeling caused prolonged maximal LH release from cultured pituitary cells. In contrast, (Orn(2,5-NAPS))/sup 8/-GnRH, although being equipotent with the 2,4-NAPS isomer in terms of LH releasing ability, was unable to cause prolonged LH release after photoaffinity labeling. Thus, (Orn(2,4-NAPS))/sup 8/GnRH is very effective photolabeling ligand of the functionally significant pituitary GnRH receptor. Based on this compound, a pituitary peptidase resistant derivative, D-Phe/sup 6/, (Orn(2,4-NAPS))/sup 8/-GnRH-(1-9)-ethylamide, was synthesized. This derivative showed high-affinity binding to pituitary membranes with a K/sub d/ comparable to those of other GnRH analogues. A radioiodinated form of this peptide was used for pituitary GnRH-receptor labeling. This derivative labeled 59- and 57-kDa proteins in rat and 58- and 56-kDa proteins in bovine pituitary membrane preparations, respectively. This peptide also labeled pituitary GnRH receptors in the solubilized state and therefore appears to be a suitable ligand for the isolation and further characterization of the receptor.

  8. Molecular basis for vulnerability to mitochondrial and oxidative stress in a neuroendocrine CRI-G1 cell line.

    Directory of Open Access Journals (Sweden)

    Natasha Chandiramani

    2011-01-01

    Full Text Available Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases are linked to mitochondrial dysfunction, which leads to impaired cellular bioenergetics and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types.Starting with an insulinoma cell line as a model for a neuronal/endocrine cell type, we isolated a novel subclonal line (named CRI-G1-RS that was more susceptible to cell death induced by mitochondrial respiratory chain inhibitors than the parental CRI-G1 line (renamed CRI-G1-RR for clarity. Compared to parental RR cells, RS cells were also more vulnerable to direct oxidative stress, but equally vulnerable to mitochondrial uncoupling and less vulnerable to protein kinase inhibition-induced apoptosis. Thus, differential vulnerability to mitochondrial toxins between these two cell types likely reflects differences in their ability to handle metabolically generated reactive oxygen species rather than differences in ATP production/utilization or in downstream apoptotic machinery. Genome-wide gene expression analysis and follow-up biochemical studies revealed that, in this experimental system, increased vulnerability to mitochondrial and oxidative stress was associated with (1 inhibition of ARE/Nrf2/Keap1 antioxidant pathway; (2 decreased expression of antioxidant and phase I/II conjugation enzymes, most of which are Nrf2 transcriptional targets; (3 increased expression of molecular chaperones, many of which are also considered Nrf2 transcriptional targets; (4 increased expression of β cell-specific genes and transcription factors that specify/maintain β cell fate; and (5 reconstitution of glucose-stimulated insulin secretion.The molecular profile presented here will enable identification of individual genes or gene clusters that shape vulnerability to mitochondrial dysfunction and

  9. Prolactin and natural killer cells: evaluating the neuroendocrine-immune axis in women with primary infertility and recurrent spontaneous abortion.

    Science.gov (United States)

    Triggianese, Paola; Perricone, Carlo; Perricone, Roberto; De Carolis, Caterina

    2015-01-01

    An association between serum prolactin (PRL) and peripheral blood natural killer (NK) cells has been described in healthy women. We explored for the first time the PRL response to the thyrotrophin-releasing hormone (TRH) test and the association between PRL and NK cells in women with reproductive failure. A total of 130 women [31 primary infertility, 69 recurrent spontaneous abortion (RSA), and 30 fertile women] were evaluated by a TRH test to analyze the following: basal PRL (bPRL), peak-time PRL, PRL absolute and relative increase, decline-time PRL. Hyperprolactinaemia (HPRL) was defined as bPRL ≥15 ng/mL. NK cells were characterized by immunophenotyping. Significantly higher bPRL levels were found in the infertile women than in controls. Both the infertile and the RSA women showed significantly elevated NK levels. bPRL levels correlated with NK cells in HPRL-infertile women. In patients with HPRL, an association between NK cell and bPRL results. The dynamic test in the infertile women would help in the management of the pregnancy impairment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Interplay of CREB and ATF2 in Ionizing Radiation-Induced Neuroendocrine Differentiation of Prostate Cancer Cells

    Science.gov (United States)

    2012-06-01

    regulatory networks in Saccharomyces cerevisiae . Science 298, 799–804 Second NES in N Terminus of ATF2 8632 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 287...C4-2B or LN3) or VCaP cells were cultured in androgen-free medium in the presence or absence of the Hh inhibitor, cyclopamine. Smoothened (Smo) siRNA...To determine how these clones respond to androgen depletion treatment, we treated cells in phenol-free medium supplemented with 10% CD-FBS for 3

  11. Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells

    Directory of Open Access Journals (Sweden)

    Huang Haining

    2009-03-01

    Full Text Available Abstract In AtT-20 cells ACTH secretion is regulated by both Ca2+ and G proteins. We previously demonstrated that calnuc, an EF-hand Ca2+ binding protein which regulates Alzheimer's β-amyloid precursor protein (APP biogenesis, binds both Ca2+ as well as Gα subunits. Here we investigate calnuc's role in G protein-mediated regulation of ACTH secretion in AtT-20 neuroendocrine secretory cells stably overexpressing calnuc-GFP. Similar to endogenous calnuc, calnuc-GFP is mainly found in the Golgi, on the plasma membrane (PM, and associated with regulated secretion granules (RSG. By deconvolution immunofluorescence, calnuc-GFP partially colocalizes with Gαi1/2 and Gαi3 at the PM and on RSG. Cytosolic calnuc(ΔSS-CFP with the signal sequence deleted also partially colocalizes with RSG and partially cosediments with Gαi1/2 in fractions enriched in RSG. Overexpression of calnuc-GFP specifically increases the distribution of Gαi1/2 on the PM whereas the distribution of Gβ subunits and synaptobrevin 2 (Vamp 2 is unchanged. Overexpression of calnuc-GFP or cytosolic calnuc(ΔSS-CFP enhances ACTH secretion two-fold triggered by mastoparan or GTPγS but does not significantly affect glycosaminoglycan (GAG chain secretion along the constitutive pathway or basal secretion of ACTH. Calnuc's facilitating effects on ACTH secretion are decreased after introducing anti-Gαi1/2, Gαi3, Gβ or calnuc IgG into permeabilized cells but not when Gα12 or preimmune IgG is introduced. The results suggest that calnuc binds to Gα subunits on the Golgi and on RSG and that overexpression of calnuc causes redistribution of Gαi subunits to the PM and RSG, indicating that calnuc plays a role in dynamic distribution of only Gα but not Gβ subunits. Thus calnuc may connect G protein signaling and calcium signaling during regulated secretion.

  12. Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

    DEFF Research Database (Denmark)

    Juul, A; Müller, J; Skakkebaek, N E

    1997-01-01

    antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH...

  13. Tracer development for detection and characterization of neuroendocrine tumors with PET

    NARCIS (Netherlands)

    Neels, Olivier Christiaan

    2008-01-01

    Neuroendocrine tumors are slowly growing tumors which originate from neuroendocrine cells. These tumors can secrete several products. In case of overproduction of serotonin, symptoms such as flushing, diarrhea and right-sided heart disease can occur. Next to serotonin, other well known products are

  14. Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

    Science.gov (United States)

    Yamada, Yoshiaki; Nakamura, Kogenta; Aoki, Shigeyuki; Taki, Tomohiro; Matsubara, Hiroyuki; Sai, Shotoku; Naruse, Katsuya; Tobiume, Motoi; Katsuda, Remi; Zennami, Kenji; Honda, Nobuaki; Nakagawa, Atsuko; Ikeda, Hiroshi

    2006-05-01

    We evaluated the usefulness of overexpression of neuroendrocrine (NE) cell differentiation determined by immunohistochemical staining for chromogranin A (Cg A) in diagnostic needle biopsy specimens of bone metastatic prostate cancers. A total of 50 patients diagnosed as having bone metastatic prostate cancer were studied. The period of observation was between 6.9 and 79.4 months (median 48.7 months). Cg A was detected by immunostaining using the labeled streptavidin biotin method. Cg A-positivity was defined as the presence of immunostained cells in 10% or more of the tumor. All statistical analyses were carried out using the Statistical Package for Social Sciences Software, version 10.0 for Windows. Eleven patients (22%) were classified into the Cg A-positive group. There were no significant differences in clinical data between the Cg A-positive and Cg A-negative groups. The 5-year cause-specific survival rate was 34.1% for the Cg A-positive group and 55.2% for the Cg A-negative group (p=0.3763). The 3-year non-recurrence rate was 9.1% for the Cg A-positive group and 35.9% for the Cg A-negative group, and this difference was significant (p=0.0253). The 3-year cause-specific survival rates after recurrence were 38.4% and 42.3% respectively (p=0.8125). We consider that NE cell differentiation of the primary tumor in cases of bone metastatic prostate cancer is not a prognostic factor for outcome.

  15. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  16. The cell non-autonomous function of ATG-18 is essential for neuroendocrine regulation of Caenorhabditis elegans lifespan.

    Science.gov (United States)

    Minnerly, Justin; Zhang, Jiuli; Parker, Thomas; Kaul, Tiffany; Jia, Kailiang

    2017-05-01

    Dietary restriction (DR) and reduced insulin growth factor (IGF) signaling extend lifespan in Caenorhabditis elegans and other eukaryotic organisms. Autophagy, an evolutionarily conserved lysosomal degradation pathway, has emerged as a central pathway regulated by various longevity signals including DR and IGF signaling in promoting longevity in a variety of eukaryotic organisms. However, the mechanism remains unclear. Here we show that the autophagy protein ATG-18 acts cell non-autonomously in neuronal and intestinal tissues to maintain C. elegans wildtype lifespan and to respond to DR and IGF-mediated longevity signaling. Moreover, ATG-18 activity in chemosensory neurons that are involved in food detection sufficiently mediates the effect of these longevity pathways. Additionally, ATG-18-mediated cell non-autonomous signaling depends on the release of neurotransmitters and neuropeptides. Interestingly, our data suggest that neuronal and intestinal ATG-18 acts in parallel and converges on unidentified neurons that secrete neuropeptides to regulate C. elegans lifespan through the transcription factor DAF-16/FOXO in response to reduced IGF signaling.

  17. Dynamin-2 regulates fusion pore expansion and quantal release through a mechanism that involves actin dynamics in neuroendocrine chromaffin cells.

    Directory of Open Access Journals (Sweden)

    Arlek M González-Jamett

    Full Text Available Over the past years, dynamin has been implicated in tuning the amount and nature of transmitter released during exocytosis. However, the mechanism involved remains poorly understood. Here, using bovine adrenal chromaffin cells, we investigated whether this mechanism rely on dynamin's ability to remodel actin cytoskeleton. According to this idea, inhibition of dynamin GTPase activity suppressed the calcium-dependent de novo cortical actin and altered the cortical actin network. Similarly, expression of a small interfering RNA directed against dynamin-2, an isoform highly expressed in chromaffin cells, changed the cortical actin network pattern. Disruption of dynamin-2 function, as well as the pharmacological inhibition of actin polymerization with cytochalasine-D, slowed down fusion pore expansion and increased the quantal size of individual exocytotic events. The effects of cytochalasine-D and dynamin-2 disruption were not additive indicating that dynamin-2 and F-actin regulate the late steps of exocytosis by a common mechanism. Together our data support a model in which dynamin-2 directs actin polymerization at the exocytosis site where both, in concert, adjust the hormone quantal release to efficiently respond to physiological demands.

  18. Chicken GnRH II occurs together with mammalian GnRH in a South American species of marsupial (Monodelphis domestica).

    Science.gov (United States)

    King, J A; Hinds, L A; Mehl, A E; Saunders, N R; Millar, R P

    1990-01-01

    Two molecular forms of gonadotropin-releasing hormone (GnRH) were demonstrated in hypothalamic extracts of M. domestica using high performance liquid chromatography and radioimmunoassay with specific GnRH antisera. One form eluted in the same position as synthetic mammalian GnRH and was quantified equally by two mammalian GnRH antisera, while the second form coeluted with synthetic chicken GnRH II and was quantified equally with two chicken GnRH II antisera. The finding of chicken GnRH II in a South American species of marsupial, which has previously been reported in some Australian species of marsupial and in species of Aves, Reptilia, Amphibia, Osteichthyes and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH.

  19. GnRH antagonist versus long agonist protocols in IVF

    DEFF Research Database (Denmark)

    Lambalk, C B; Banga, F R; Huirne, J A

    2017-01-01

    was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... METHODS: The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols...... the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing pregnancy rate when the oral hormonal programming pill (OHP...

  20. GnRH tandem peptides for inducing an immunogenic response to GnRH-I without cross-reactivity to other GnRH isoforms

    NARCIS (Netherlands)

    Turkstra, J.A.; Schaaper, W.M.M.; Oonk, H.B.; Meloen, R.H.

    2005-01-01

    Gonadotropin releasing hormone (GnRH) occurs in various isoforms in mammals, i.e. GnRH-I (mammalian GnRH), GnRH-II (chicken GnRH-II), GnRH-III (salmon GnRH) and two forms of lamprey GnRH. The function of the latter four molecules have only been partially investigated. Also not much is known about

  1. Tracking Ca2+-dependent and Ca2+-independent conformational transitions in syntaxin 1A during exocytosis in neuroendocrine cells.

    Science.gov (United States)

    Greitzer-Antes, Dafna; Barak-Broner, Noa; Berlin, Shai; Oron, Yoram; Chikvashvili, Dodo; Lotan, Ilana

    2013-07-01

    A key issue for understanding exocytosis is elucidating the various protein interactions and the associated conformational transitions underlying soluble N-ethylmeleimide-sensitive factor attachment protein receptor (SNARE) protein assembly. To monitor dynamic changes in syntaxin 1A (Syx) conformation along exocytosis, we constructed a novel fluorescent Syx-based probe that can be efficiently incorporated within endogenous SNARE complexes, support exocytosis, and report shifts in Syx between 'closed' and 'open' conformations by fluorescence resonance energy transfer analysis. Using this probe we resolve two distinct Syx conformational transitions during membrane depolarization-induced exocytosis in PC12 cells: a partial 'opening' in the absence of Ca(2+) entry and an additional 'opening' upon Ca(2+) entry. The Ca(2+)-dependent transition is abolished upon neutralization of the basic charges in the juxtamembrane regions of Syx, which also impairs exocytosis. These novel findings provide evidence of two conformational transitions in Syx during exocytosis, which have not been reported before: one transition directly induced by depolarization and an additional transition that involves the juxtamembrane region of Syx. The superior sensitivity of our probe also enabled detection of subtle Syx conformational changes upon interaction with VAMP2, which were absolutely dependent on the basic charges of the juxtamembrane region. Hence, our results further suggest that the Ca(2+)-dependent transition in Syx involves zippering between the membrane-proximal juxtamembrane regions of Syx and VAMP2 and support the recently implied existence of this zippering in the final phase of SNARE assembly to catalyze exocytosis.

  2. Chromatographic and immunological evidence for mammalian GnRH and chicken GnRH II in eel (Anguilla anguilla) brain and pituitary.

    Science.gov (United States)

    King, J A; Dufour, S; Fontaine, Y A; Millar, R P

    1990-01-01

    Gonadotropin-releasing hormone (GnRH) peptides in the brain and pituitary of the European eel (Anguilla anguilla) were investigated by reverse phase high performance liquid chromatography (HPLC) and radioimmunoassay with region-specific antisera. Two GnRH molecular forms were demonstrated in brain and pituitary extracts. One form eluted in the same position as synthetic mammalian GnRH on HPLC and was recognized by antibodies directed against the NH2 and COOH termini of mammalian GnRH as well as by antibodies to the middle region. The second form eluted in the same position as synthetic chicken GnRH II and was recognized by specific antibodies to this molecule. Salmon GnRH and chicken GnRH I were not detected. The occurrence of mammalian GnRH in teleost fish suggests that this molecular form is more ancient than was previously suspected and arose earlier than in primitive tetrapods, or that it has arisen in the eel through random mutation of salmon GnRH. The lack of salmon GnRH in the eel brain indicates that this molecular form is not common to all teleost species. The finding in eel brain of chicken GnRH II, which has previously been described in species of Mammalia, Aves, Reptilia, Amphibia, Osteichthyes, and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH.

  3. Pitfalls in the diagnosis of neuroendocrine tumors: atypical clinical and radiological findings as cause of medical mistakes.

    Science.gov (United States)

    Bajetta, Emilio; Catena, Laura; Ducceschi, Monika; Pusceddu, Sara; Milione, Massimo; Maccauro, Marco; Bajetta, Roberto; Procopio, Giuseppe; Buzzoni, Roberto; Formisano, Barbara; Di Guardo, Lorenza; Platania, Marco

    2009-01-01

    Carcinoids are infrequent neoplasms arising from neuroendocrine cells. Due to blurred symptoms and the presence of equivocal diagnostic findings, these tumors are sometimes misdiagnosed. Therefore, increased rates of false neuroendocrine tumors represent an emerging problem in clinical practice. Our aim is to alert clinicians on this matter by supplying them with useful warnings. In the specialized neuroendocrine tumor study Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a neuroendocrine tumor have been recognized as having false neuroendocrine tumors. The related clinical and instrumental findings leading to a previous wrong neuroendocrine tumor diagnosis are reported. From July 2006 to December 2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the remaining 80 cases a correct Net diagnosis was carried out. Watchful differential diagnoses and skill appraisal of laboratory investigations resulted in: chronic atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases), estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome (1), and sarcoidosis (1). Neuroendocrine tumors are still relatively known clinical entities. To discriminate false neuroendocrine tumors from neuroendocrine tumors requires a good expertise and a large daily practice with the disease. Good knowledge and skillfulness in identifying biochemical alterations and false radiological positive results could avoid both patient inconvenience and very expensive workup. The importance of a multidisciplinary approach in specialized centers is emphasized.

  4. A second form of gonadotropin-releasing hormone (GnRH), with chicken GnRH II-like properties, occurs together with mammalian GnRH in marsupial brains.

    Science.gov (United States)

    King, J A; Mehl, A E; Tyndale-Biscoe, C H; Hinds, L; Millar, R P

    1989-11-01

    GnRH peptides in the hypothalami of marsupials (tammar wallaby, short-nosed bandicoot, and eastern quoll) and a monotreme (echidna) were investigated by reverse phase HPLC and RIA with region-specific antisera. In the wallaby hypothalamic extract, a single form of GnRH was present, which eluted in the same position as synthetic mammalian GnRH on HPLC and was recognized by antibodies directed against the NH2- and COOH-termini of mammalian GnRH as well as by antibodies to the middle region. Two GnRH molecular forms were demonstrated in the bandicoot and quoll hypothalamic extracts. One form eluted in the same position as synthetic mammalian GnRH on HPLC and was quantified equally by two mammalian GnRH antisera. The second form eluted in the same position as synthetic chicken GnRH II and was recognized by specific antibodies to this molecule. Quantification of this immunoreactive peak with two chicken GnRH II antisera was not equal, suggesting that the peptide has similar properties to, but may not be identical to, chicken GnRH II. Immunoreactive GnRH was also detected in the echidna hypothalamic extract. These findings demonstrate that in some mammals more than one form of GnRH is present in the brain of a single species, as has previously been found in species from all nonmammalian vertebrate classes. The finding in marsupial brain of a peptide with properties of chicken GnRH II, which has previously been reported in species of Aves, Reptilia, Amphibia, Osteichthyes, and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early early evolved and conserved form of GnRH.

  5. Neuroendocrine control of ionic balance in zebrafish.

    Science.gov (United States)

    Kwong, Raymond W M; Kumai, Yusuke; Perry, Steve F

    2016-08-01

    Zebrafish (Danio rerio) is an emerging model for integrative physiological research. In this mini-review, we discuss recent advances in the neuroendocrine control of ionic balance in this species, and identify current knowledge gaps and issues that would benefit from further investigation. Zebrafish inhabit a hypo-ionic environment and therefore are challenged by a continual loss of ions to the water. To maintain ionic homeostasis, they must actively take up ions from the water and reduce passive ion loss. The adult gill or the skin of larvae are the primary sites of ionic regulation. Current models for the uptake of major ions in zebrafish incorporate at least three types of ion transporting cells (also called ionocytes); H(+)-ATPase-rich cells for Na(+) uptake, Na(+)/K(+)-ATPase-rich cells for Ca(2+) uptake, and Na(+)/Cl(-)-cotransporter expressing cells for both Na(+) and Cl(-) uptake. The precise molecular mechanisms regulating the paracellular loss of ions remain largely unknown. However, epithelial tight junction proteins, including claudins, are thought to play a critical role in reducing ion losses to the surrounding water. Using the zebrafish model, several key neuroendocrine factors were identified as regulators of epithelial ion movement, including the catecholamines (adrenaline and noradrenaline), cortisol, the renin-angiotensin system, parathyroid hormone and prolactin. Increasing evidence also suggests that gasotransmitters, such as H2S, are involved in regulating ion uptake. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Pasupuleti Prathima

    2016-11-01

    Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

  7. Immune-Neuroendocrine Interactions: Evolution, Ecology, and Susceptibility to Illness.

    Science.gov (United States)

    Blom, Johanna M C; Ottaviani, Enzo

    2017-11-16

    The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latter, the principle player is the lymphocyte. Immunocytes are characterized by the presence of pro-opiomelanocortin (POMC) peptides, CRH, and other molecules that display a significant similarity to their mammalian counterparts regarding their functions, as both are mainly involved in fundamental functions such as immune (chemotaxis, phagocytosis, cytotoxicity, etc.) and neuroendocrine (stress) responses. Furthermore, the immune-neuroendocrine system provides vital answers to ecological and immunological demands in terms of economy and efficiency. Finally, susceptibility to disease emerges as the result of a continuous dynamic interaction between the world within and the world outside. New fields such as ecological immunology study the susceptibility to pathogens in an evolutionary perspective while the field of neuro-endocrine-immunology studies the susceptibility from a more immediate perspective.

  8. Unusual apocrine carcinoma with neuroendocrine differentiation: a cutaneous neoplasm may be analogous to neuroendocrine carcinoma with apocrine differentiation of breast.

    Science.gov (United States)

    Li, Yang; Chen, Li-li; Li, Bin; Tian, Xiao-ying; Li, Zhi

    2015-06-10

    Cutaneous apocrine carcinoma (AC) is a rare adnexal neoplasm that histologically can mimic breast carcinoma metastatic to the skin or apocrine carcinoma arising in ectopic breast tissue. As extremely rare condition, neuroendocrine differentiation may be observed in AC although its etiology and pathogenesis is still unclear. We report here a case of unusual AC with neuroendocrine differentiation in right labium majus pudenda. A 43-year-old woman presented with a 6-month history of an asymptomatic pea-sized brownish nodule in right labium majus pudenda without enlargement of inguinal lymph nodes and bilateral breast nodules. The mass was totally resected. Microscopically, the tumor was solitary and located in the deep dermis without epidermal connection. Tumor cells were arranged in a micronodular or formed massive solid nests separated by densely fibroblastic stroma. Scattered glandular or rosette-like structures were identified within the tumor nodules. Immunohistochemically, the tumor cells were diffusely positive to CK7, CEA, GCDFP-15, synaptophysin, estrogen and progesterone receptors. Part of tumor cells expressed androgen receptor, but they were negative to CK20, CK5/6, p63 and S-100. Because of its rarity and histogenesis complexity, there exist diagnostic challenges for pathologists to differentiate cutaneous AC with neuroendocrine differentiation from other carcinomas with apocrine or neuroendocrine features. Our case demonstrates that the tumor shares some features with mammary carcinoma and might originate from mammary-like sweat gland in anogenital region. The results suggest that, for the first time, primary cutaneous AC with neuroendocrine differentiation may be analogous to the mammary neuroendocrine carcinoma with apocrine differentiation in histological feature and biological behavior. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7732276716685708.

  9. Neuroendocrine effects of cytokines in the rat.

    Science.gov (United States)

    Rivier, C

    1993-01-01

    The necessity ot maintain and/or restore homeostasis is an essential feature of mammals. This requires complex interactions between body cells, such as those from the immune and neuroendocrine systems, and in particular implies that the occurrence of immune activation be conveyed to the brain. It is now widely recognized that following infection, injury or inflammation, some immune cells (particularly macrophages) produce polypeptides called cytokines, interleukins or lymphokines /48/. These proteins provide the basis for intercellular communication between leukocytes (hence the name "interleukins") and mediate the immunoinflammatory responses (in particular T and B lymphocyte proliferation) /4,177/. In addition, interleukins (IL) can enter the general circulation and reach cells of the neuroendocrine axes, a phenomenon which represents one arm of the bidirectional communication links between the immune and the endocrine systems /25/. The early events which take place after presentation of an antigen (the so-called "acute-phase response" /89/) include metabolic and endocrine changes, such as changes in the circulating levels of insulin, TSH, GH, LH and ACTH, as well as adrenal and gonadal steroids /7,14/. This article reviews our present state of knowledge with regard to the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes of the rodent in response to interleukins.

  10. Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity

    Science.gov (United States)

    León, Silvia; Barroso, Alexia; Vázquez, María J.; García-Galiano, David; Manfredi-Lozano, María; Ruiz-Pino, Francisco; Heras, Violeta; Romero-Ruiz, Antonio; Roa, Juan; Schutz, Günther; Kirilov, Milen; Gaytan, Francisco; Pinilla, Leonor; Tena-Sempere, Manuel

    2016-01-01

    Kisspeptins, ligands of the receptor, Gpr54, are potent stimulators of puberty and fertility. Yet, whether direct kisspeptin actions on GnRH neurons are sufficient for the whole repertoire of their reproductive effects remains debatable. To dissect out direct vs. indirect effects of kisspeptins on GnRH neurons in vivo, we report herein the detailed reproductive/gonadotropic characterization of a Gpr54 null mouse line with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54−/−Tg; rescued). Despite preserved fertility, adult rescued mice displayed abnormalities in gonadal microstructure, with signs of precocious ageing in females and elevated LH levels with normal-to-low testosterone secretion in males. Gpr54−/−Tg rescued mice showed also altered gonadotropin responses to negative feedback withdrawal, while luteinizing hormone responses to various gonadotropic regulators were variably affected, with partially blunted relative (but not absolute) responses to kisspeptin-10, NMDA and the agonist of tachykinin receptors, NK2R. Our data confirm that direct effects of kisspeptins on GnRH cells are sufficient to attain fertility. Yet, such direct actions appear to be insufficient to completely preserve proper functionality of gonadotropic axis, suggesting a role of kisspeptin signaling outside GnRH cells. PMID:26755241

  11. Neuroendocrine differentiation in a case of cervical cancer | Rashed ...

    African Journals Online (AJOL)

    tumor; that further showed neuroendocrine differentiation, as demonstrated by chromogranin-A positivity. It is important to differentiate small cell carcinoma from other malignant tumors of the uterine cervix. Morphological features play an important role in making a diagnosis and the immunohistochemistry study can offer an ...

  12. Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs.

    Science.gov (United States)

    Tello, Javier A; Kohout, Trudy; Pineda, Rafael; Maki, Richard A; Scott Struthers, R; Millar, Robert P

    2013-07-01

    The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mice revealed a severe reduction (7- to 8-fold) compared with the mouse Gnrhr1 in wild-type mice. ¹²⁵I-GnRH binding assays on pituitary membrane fractions corroborated reduced human GNRHR1 protein expression in ki/ki mice, as occurs with transfection of human GNRHR1 in cell lines. Female homozygous knock-in mice displayed normal pubertal onset, indicating that a large reduction in GNRHR1 expression is sufficient for this process. However, ki/ki females exhibited periods of prolonged estrous and/or metestrous and reduced fertility. No impairment was found in reproductive maturity or adult fertility in male ki/ki mice. Interestingly, the serum LH response to GnRH challenge was reduced in both knock-in males and females, indicating a reduced GNRHR1 signaling capacity. Small molecules targeting human GPCRs usually have poor activities at homologous rodent receptors, thus limiting their use in preclinical development. Therefore, we tested a human-specific GnRH1 antagonist, NBI-42902, in our mouse model and demonstrated abrogation of a GnRH1-induced serum LH rise in ki/ki mice and an absence of effect in littermates expressing the wild-type murine receptor. This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs.

  13. Reclassification of neuroendocrine tumors improves the separation of carcinoids and the prediction of survival

    DEFF Research Database (Denmark)

    Skov, B.G.; Krasnik, M.; Lantuejoul, S.

    2008-01-01

    INTRODUCTION: The classification of neuroendocrine lung tumors has changed over the last decades. Reliable diagnoses are crucial for the quality of clinical databases. The purpose of this study is to determine to which extent the use of different diagnostic criteria of neuroendocrine lung tumors.......03). However, the number of removed lymph nodes were insufficient for definitive determination of the prognostic impact of node metastases. Regarding the revised diagnoses, a significant difference in survival between typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell...

  14. Recent Development of Non-Peptide GnRH Antagonists

    Directory of Open Access Journals (Sweden)

    Feng-Ling Tukun

    2017-12-01

    Full Text Available The decapeptide gonadotropin-releasing hormone, also referred to as luteinizing hormone-releasing hormone with the sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 plays an important role in regulating the reproductive system. It stimulates differential release of the gonadotropins FSH and LH from pituitary tissue. To date, treatment of hormone-dependent diseases targeting the GnRH receptor, including peptide GnRH agonist and antagonists are now available on the market. The inherited issues associate with peptide agonists and antagonists have however, led to significant interest in developing orally active, small molecule, non-peptide antagonists. In this review, we will summarize all developed small molecule GnRH antagonists along with the most recent clinical data and therapeutic applications.

  15. Pituitary sensitizing effect of GnRH antagonists: a mechanism explaining LH escape during IVF?

    NARCIS (Netherlands)

    Banga, F.R.; Huirne, J.A.F.; Korsen, T.; Homburg, R.R.; Hompes, P.G.A.; Lambalk, C.B.

    2010-01-01

    Background GnRH antagonists have been introduced to induce persistent LH suppression. Many studies show a gradual increase of LH levels after several days of GnRH antagonist administration, the so-called escape or rebound effect. We hypothesize that, under chronic GnRH antagonist administration, a

  16. Effects of GnRH immunization in sexually mature pony stallions

    NARCIS (Netherlands)

    Turkstra, J.A.; Meer, F.J.U.M.; Knaap, J.; Rottier, P.J.M.; Teerds, K.J.; Colenbrander, B.; Meloen, R.H.

    2005-01-01

    Immunization against gonadotrophin releasing hormone (GnRH) was studied as an alternative for the commonly used surgical castration in stallions. Two GnRH vaccines comprising non-mineral oil adjuvants were evaluated for their potential to induce high antibody titers directed against GnRH and

  17. Protective Role of GnRH Antagonist on Chemotherapy-induced Spermatogenesis Disorder: A Morphological Study

    Directory of Open Access Journals (Sweden)

    Daryosh Mohammadnejad

    2013-08-01

    Full Text Available Purpose: Anti cancer drugs is one of the most important chemotherapeutic factors which can influence spermatogenesis process and germinal epithelium. Since dividing cells are mainly affected by anticancer drugs, the aim of the present study is to investigate thepreventive effect of GnRH antagonist on spermatogenic defect produced by anticancer drugs. Methods: In the present study thirty adult male mice aging 6-8 weeks were divided into 3 groups as: Control, Experimental 1 and Experimental 2. Experimental 1 group received Cisplatin for 5 days as 2.5 mg/kg intraperitoneally and Experimental 2group received 0.25 mg/kg cetrorelix (GnRH antagonist one week before cisplatin treatment and continued for 3 weeks. The mice in all groups were sacrificed 35 days after the last injection and testis specimens were fixed in boueins, formaldehyde fixativeand 2.5% Glutaraldehide then prepared for light and electron microscopic examination. Results: Light microscopy (LM study showed that the number of spermatogonial cells, thickness of germinal epithelium, was decreased in Experimental 1group. Electronmicroscopy revealed that in this group several intercellular spaces appeared between spermatogenic cells and secretory granules in interstitial cells was increased. There were several vacuolated mitochondria and destroyed organelles in spermatogonial cells but inExperimental 2 group condition was similar to control group. Conclusion: These results indicate that the cetrorelix administration before cancer treatment may protect germinal epithelium against side effects of cisplatin.

  18. Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

    During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment. Copyright © 2012 S. Karger AG, Basel.

  19. Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study

    Science.gov (United States)

    2017-01-05

    Poorly Differentiated Malignant Neuroendocrine Carcinoma; Neuroendocrine Carcinoma, Grade 3; Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

  20. Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.

    Science.gov (United States)

    Tenenbaum-Rakover, Yardena; Commenges-Ducos, Monique; Iovane, André; Aumas, Chantal; Admoni, Osnat; de Roux, Nicolas

    2007-03-01

    Loss of function of the G protein-coupled receptor of kisspeptins (GPR54) was recently described as a new cause of isolated hypogonadotropic hypogonadism. In vivo studies performed in several species have confirmed the major role of kisspeptins in neuroendocrine regulation of the gonadotropic axis and therefore sexual maturation. The objective of this study was to specify the exact contribution of kisspeptins and GPR54 to the initiation of puberty in humans. Detailed neuroendocrine descriptions were performed in five patients with isolated hypogonadotropic hypogonadism bearing a new GPR54-inactivating mutation. A homozygous mutation (T305C) leading to a leucine substitution with proline (L102P) was found in the five affected patients. This substitution completely inhibited GPR54 signaling. Phenotypic analysis revealed variable expressivity in the same family, either partial or complete gonadotropic deficiency. LH pulsatility analysis showed peaks with normal frequency but low amplitude. Repeated GnRH tests performed between 12 and 21 yr of age in one affected male revealed progressive changes in pituitary response from an early pubertal to an almost full pubertal pattern. Double GnRH test stimulations performed at a 120-min interval showed reduced dynamic pituitary response in GPR54-mutated patients. GPR54 inactivation does not impede neuroendocrine onset of puberty; rather, it delays and slows down pubertal maturation of the gonadotropic axis. The L102P loss of function mutation in GPR54 results in a more quantitative than qualitative defect of gonadotropic axis activation.

  1. Dynamic GnRH- and hCG-testing

    DEFF Research Database (Denmark)

    Bang, A Kirstine; Nordkap, Loa; Almstrup, Kristian

    2017-01-01

    1. OBJECTIVE: Gonadotropin-releasing hormone (GnRH) and Human Chorionic Gonadotropin (hCG) stimulation-tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and Testosterone after GnRH...... and hCG stimulation in healthy men, and assess the impact of six single nucleotide polymorphisms on the responses. 2. DESIGN: GnRH- and hCG-stimulation tests were performed on 77 healthy men, 18-40 years (reference group) at a specialized andrology referral center. The potential use of the tests...... and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4-58.8 U/L and 0.2-11.8 U/L, FSH decreased in nine men. Testosterone increased approximately 110% (range 18.7-67.6 nmol/l) during hCG-testing. None of the polymorphisms had any major impact on the test results...

  2. Pharmacological and toxicological assessment of a potential GnRH vaccine in young-adult male pigs

    NARCIS (Netherlands)

    Turkstra, J.A.; Staay, van der F.J.; Stockhofe-Zurwieden, N.; Woelders, H.; Meloen, R.H.; Schuurman, T.

    2011-01-01

    Active immunization against gonadotrophin-releasing hormone (GnRH) is successfully applied to prevent boar taint in pork. In men, GnRH immunization could be an alternative to hormone therapy in patients with prostate cancer. In this study, a new GnRH vaccine formulation (a modified GnRH peptide

  3. LH-independent testosterone secretion is mediated by the interaction between GNRH2 and its receptor within porcine testes

    Science.gov (United States)

    Unlike the classical gonadotropin-releasing hormone (GNRH1), the second mammalian isoform (GNRH2) is an ineffective stimulant of gonadotropin release. Species that produce GNRH2 may not maintain a functional GNRH2 receptor (GNRHR2) due to coding errors. A full length GNRHR2 gene has been identified ...

  4. Functional imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Loft, Annika

    2010-01-01

    UNLABELLED: Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In......-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), and (18)F-FDG PET. METHODS: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET on average within 40 d. The functional images were fused with low......-positive, of which 3 were also (123)I-MIBG scintigraphy-positive, giving a combined overall sensitivity of 96%. SRS also exceeded (123)I-MIBG scintigraphy and (18)F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. (123)I-MIBG scintigraphy was superior to (18)F...

  5. Towards a unified model of neuroendocrine-immune interaction.

    Science.gov (United States)

    Petrovsky, N

    2001-08-01

    Although the neuroendocrine system has immunomodulating potential, studies examining the relationship between stress, immunity and infection have, until recently, largely been the preserve of behavioural psychologists. Over the last decade, however, immunologists have begun to increasingly appreciate that neuroendocrine-immune interactions hold the key to understanding the complex behaviour of the immune system in vivo. The nervous, endocrine and immune systems communicate bidirectionally via shared messenger molecules variously called neurotransmitters, cytokines or hormones. Their classification as neurotransmitters, cytokines or hormones is more serendipity than a true reflection of their sphere of influence. Rather than these systems being discrete entities we would propose that they constitute, in reality, a single higher-order entity. This paper reviews current knowledge of neuroendocrine-immune interaction and uses the example of T-cell subset differentiation to show the previously under-appreciated importance of neuroendocrine influences in the regulation of immune function and, in particular, Th1/Th2 balance and diurnal variation there of.

  6. The role of GABA in the regulation of GnRH neurons

    Directory of Open Access Journals (Sweden)

    Miho eWatanabe

    2014-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.

  7. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...... occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  8. Androgen deprivation of the PC-310 [correction of prohormone convertase-310] human prostate cancer model system induces neuroendocrine differentiation

    NARCIS (Netherlands)

    J. Jongsma (Johan); M.H. Oomen; M.A. Noordzij (Marinus); W.M. van Weerden (Wytske); G.J. Martens; Th.H. van der Kwast (Theo); F.H. Schröder (Fritz); G.J. van Steenbrugge (Gert Jan)

    2000-01-01

    textabstractNeuroendocrine (NE) cells are androgen-independent cells and secrete growth-modulating neuropeptides via a regulated secretory pathway (RSP). We studied NE differentiation after androgen withdrawal in the androgen-dependent prostate cancer xenograft PC-310.

  9. 60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of portal vessels and self-priming.

    Science.gov (United States)

    Fink, George

    2015-08-01

    Geoffrey Harris, while still a medical student at Cambridge, was the first researcher (1937) to provide experimental proof for the then tentative view that the anterior pituitary gland was controlled by the CNS. The elegant studies carried out by Harris in the 1940s and early 1950s, alone and in collaboration with John Green and Dora Jacobsohn, established that this control was mediated by a neurohumoral mechanism that involved the transport by hypophysial portal vessel blood of chemical substances from the hypothalamus to the anterior pituitary gland. The neurohumoral control of anterior pituitary secretion was proved by the isolation and characterisation of the 'chemical substances' (mainly neuropeptides) and the finding that these substances were released into hypophysial portal blood in a manner consistent with their physiological functions. The new discipline of neuroendocrinology - the way that the brain controls endocrine glands and vice versa - revolutionised the treatment of endocrine disorders such as growth and pubertal abnormalities, infertility and hormone-dependent tumours, and it underpins our understanding of the sexual differentiation of the brain and key aspects of behaviour and mental disorder. Neuroendocrine principles are illustrated in this Thematic Review by way of Harris' major interest: hypothalamic-pituitary-gonadal control. Attention is focussed on the measurement of GnRH in hypophysial portal blood and the role played by the self-priming effect of GnRH in promoting the onset of puberty and enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory gonadotrophin surge in humans and other spontaneously ovulating mammals. © 2015 Society for Endocrinology.

  10. Kisspeptin Can Stimulate Gonadotropin-Releasing Hormone (GnRH) Release by a Direct Action at GnRH Nerve Terminals

    Science.gov (United States)

    d'Anglemont de Tassigny, Xavier; Fagg, Lisa A.; Carlton, Mark B. L.; Colledge, William H.

    2008-01-01

    The G protein-coupled receptor GPR54, and its peptide ligand kisspeptin (Kp), are crucial for the induction and maintenance of mammalian reproductive function. GPR54 is expressed by GnRH neurons and is directly activated by Kp to stimulate GnRH release. We hypothesized that Kp may be able to act at the GnRH nerve terminals located in the mediobasal hypothalamus (MBH) region. To test this hypothesis, we used organotypic culture of MBH explants challenged with Kp, followed by RIA to detect GnRH released into the cultured medium. Kp stimulation for 1 h induced GnRH release from wild-type male MBH in a dose-dependent manner, whereas this did not occur in MBH explants isolated from Gpr54 null mice. Continuous Kp stimulation caused a sustained GnRH release for 4 h, followed by a decrease of GnRH release, suggesting a desensitization of GPR54 activity. Tetrodotoxin did not alter the Kp-induced GnRH release, indicating that Kp can act directly at the GnRH nerve terminals. To localize Gpr54 expression within the MBH, we used transgenic mice, in which Gpr54 expression is tagged with an IRES-LacZ reporter gene and can be visualized by β-galactosidase staining. Gpr54 expression was detected outside of the median eminence, in the pars tuberalis. In conclusion, our results provide evidence for a potent stimulating effect of Kp at GnRH nerve terminals in the MBH of the mouse. This study suggests a new point at which Kp can act on GnRH neurons. PMID:18450966

  11. Reproductive neuroendocrine pathways of social behavior

    Directory of Open Access Journals (Sweden)

    Ishwar eParhar

    2016-03-01

    Full Text Available Social behaviors are key components of reproduction because they are essential for successful fertilization. Social behaviors such as courtship, mating, and aggression are strongly associated with sex steroids, such as testosterone, estradiol and progesterone. Secretion of sex steroids from the gonads is regulated by the hypothalamus-pituitary-gonadal (HPG axis in vertebrates. Gonadotropin-releasing hormone (GnRH is a pivotal hypothalamic neuropeptide that stimulates gonadotropin release from the pituitary. In recent years, the role of neuropeptides containing the C-terminal Arg-Phe-NH2 (RFamide peptides has been emphasized in vertebrate reproduction. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH, emerged as critical accelerator and suppressor of gonadotropin secretion. Kisspeptin stimulates GnRH release by directly acting on GnRH neurons, whereas GnIH inhibits gonadotropin release by inhibiting kisspeptin or GnRH neurons or pituitary gonadotropes. These neuropeptides can regulate social behavior by regulating the HPG axis. However, distribution of neuronal fibers of GnRH, kisspeptin and GnIH neurons are not limited within the hypothalamus, and the existence of extra-hypothalamic neuronal fibers suggests direct control of social behavior within the brain. It has traditionally been shown that central administration of GnRH can stimulate female sexual behavior in rats. Recently, it was shown that Kiss1, one of the paralogs of kisspeptin peptide family, regulates fear responses in zebrafish and GnIH inhibits socio-sexual behavior in birds. Here we highlight recent findings regarding the role of GnRH, kisspeptin and GnIH in the regulation of social behaviors in fish, birds and mammals and discuss their importance in future biological and biomedical research.

  12. An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1–7 Cells for Evaluation of the Neuroendocrine Effects of Essential Oils

    Directory of Open Access Journals (Sweden)

    Dai Mizuno

    2015-01-01

    Full Text Available Aromatherapy and plant-based essential oils are widely used as complementary and alternative therapies for symptoms including anxiety. Furthermore, it was reportedly effective for the care of several diseases such as Alzheimer’s disease and depressive illness. To investigate the pharmacological effects of essential oils, we developed an in vitro assay system using immortalized hypothalamic neuronal cells (GT1–7 cells. In this study, we evaluated the effects of essential oils on neuronal death induced by hydrogen peroxide (H2O2, aluminum, zinc, or the antagonist of estrogen receptor (tamoxifen. Among tests of various essential oils, we found that H2O2-induced neuronal death was attenuated by the essential oils of damask rose, eucalyptus, fennel, geranium, ginger, kabosu, mandarin, myrrh, and neroli. Damask rose oil had protective effects against aluminum-induced neurotoxicity, while geranium and rosemary oil showed protective activity against zinc-induced neurotoxicity. In contrast, geranium oil and ginger oil enhanced the neurotoxicity of tamoxifen. Our in vitro assay system could be useful for the neuropharmacological and endocrine pharmacological studies of essential oils.

  13. INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity.

    Science.gov (United States)

    Rooper, Lisa M; Sharma, Rajni; Li, Qing Kay; Illei, Peter B; Westra, William H

    2017-11-01

    Despite the importance of recognizing neuroendocrine differentiation when diagnosing tumors of the thoracic cavity, the sensitivity of traditional neuroendocrine markers is suboptimal, particularly for high-grade neuroendocrine carcinomas such as small cell lung carcinoma and large cell neuroendocrine carcinoma. To increase sensitivity, neuroendocrine markers are routinely ordered as panels of multiple immunostains where any single positive marker is regarded as sufficient evidence of neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a well-validated transcription factor of neuroendocrine differentiation that has only recently been evaluated for diagnostic use. We performed INSM1 immunohistochemistry on a large series of thoracic neuroendocrine and non-neuroendocrine tumors and compared its performance to synaptophysin, chromogranin, and CD56. INSM1 was positive in 94.9% of small cell lung carcinomas and 91.3% of large cell neuroendocrine carcinomas, compared with 74.4% and 78.3% with the combined panel of traditional markers. INSM1 also stained all (100%) of the atypical carcinoids, typical carcinoids and mediastinal paragangliomas, but only 3.3% of adenocarcinomas and 4.2% of squamous cell carcinomas. Overall, INSM1 demonstrated a sensitivity of 96.4% across all grades of thoracic neuroendocrine tumors, significantly more than the 87.4% using the panel of traditional markers (P=0.02). INSM1 is sufficiently sensitive and specific to serve as a standalone first-line marker of neuroendocrine differentiation. A more restrained approach to immunohistochemical analysis of small thoracic biopsies is appropriate given the expanding demand on this limited material for therapeutic biomarker analysis.

  14. A Neuroendocrine Carcinoma of Undetermined Origin in a Dog

    OpenAIRE

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-01-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-l...

  15. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

    Directory of Open Access Journals (Sweden)

    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  16. Gastrointestinal Surgery of Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Olsen, Ingrid Marie Holst; Knigge, Ulrich

    2015-01-01

    Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may...... be performed to reduce local or hormone-induced symptoms and to improve quality of life. The surgical procedures for GEP-NENs are accordingly described below. In most patients life-long follow-up is required, even following radical surgery, as recurrence may occur several years later....

  17. Neuronal Gonadotrophin-Releasing Hormone (GnRH) and Astrocytic Gonadotrophin Inhibitory Hormone (GnIH) Immunoreactivity in the Adult Rat Hippocampus.

    Science.gov (United States)

    Ferris, J K; Tse, M T; Hamson, D K; Taves, M D; Ma, C; McGuire, N; Arckens, L; Bentley, G E; Galea, L A M; Floresco, S B; Soma, K K

    2015-10-01

    Gonadotrophin-releasing hormone (GnRH) and gonadotrophin inhibitory hormone (GnIH) are neuropeptides secreted by the hypothalamus that regulate reproduction. GnRH receptors are not only present in the anterior pituitary, but also are abundantly expressed in the hippocampus of rats, suggesting that GnRH regulates hippocampal function. GnIH inhibits pituitary gonadotrophin secretion and is also expressed in the hippocampus of a songbird; its role outside of the reproductive axis is not well established. In the present study, we employed immunohistochemistry to examine three forms of GnRH [mammalian GnRH-I (mGnRH-I), chicken GnRH-II (cGnRH-II) and lamprey GnRH-III (lGnRH-III)] and GnIH in the adult rat hippocampus. No mGnRH-I and cGnRH-II+ cell bodies were present in the hippocampus. Sparse mGnRH-I and cGnRH-II+ fibres were present within the CA1 and CA3 fields of the hippocampus, along the hippocampal fissure, and within the hilus of the dentate gyrus. No lGnRH-III was present in the rodent hippocampus. GnIH-immunoreactivity was present in the hippocampus in cell bodies that resembled astrocytes. Males had more GnIH+ cells in the hilus of the dentate gyrus than females. To confirm the GnIH+ cell body phenotype, we performed double-label immunofluorescence against GnIH, glial fibrillary acidic protein (GFAP) and NeuN. Immunofluorescence revealed that all GnIH+ cell bodies in the hippocampus also contained GFAP, a marker of astrocytes. Taken together, these data suggest that GnRH does not reach GnRH receptors in the rat hippocampus primarily via synaptic release. By contrast, GnIH might be synthesised locally in the rat hippocampus by astrocytes. These data shed light on the sites of action and possible functions of GnRH and GnIH outside of the hypothalamic-pituitary-gonadal axis. © 2015 British Society for Neuroendocrinology.

  18. A neuroendocrine carcinoma of undetermined origin in a dog.

    Science.gov (United States)

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-09-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-like structures. Scattered small necrotic foci and invasion to fibrous septa were typically observed. Neoplastic cells showed round to oval-shaped nuclei with prominent nucleoli and abundant eosinophilic cytoplasm that were positive for Grimelius' silver impregnation staining and immunostaining with cytokeratin, synaptophysin, vasoactive intestinal peptide and chromogranin A, indicative of the development of a neuroendocrine carcinoma. However, judging from the distribution of tumors lacking the portion suggestive of the primary site in any organ examined, as well as no further indication of differentiation potential of neoplastic cells, this tumor has so far been diagnosed as neuroendocrine carcinoma of undetermined origin.

  19. Delayed puberty in spontaneously hypertensive rats involves a primary ovarian failure independent of the hypothalamic KiSS-1/GPR54/GnRH system.

    Science.gov (United States)

    Pinilla, L; Castellano, J M; Romero, M; Tena-Sempere, M; Gaytán, F; Aguilar, E

    2009-06-01

    Spontaneously hypertensive (SH) rats, extensively used as experimental models of essential human hypertension, display important alterations in the neuroendocrine reproductive axis, which manifest as markedly delayed puberty onset in females but whose basis remains largely unknown. We analyze herein in female SH rats: 1) possible alterations in the expression and function of KiSS-1/GPR54 and GnRH/GnRH-receptor systems, 2) the integrity of feedback mechanisms governing the hypothalamic-pituitary-ovarian axis, and 3) the control of ovarian function by gonadotropins. Our data demonstrate that, despite overtly delayed puberty, no significant decrease in hypothalamic KiSS-1, GPR54, or GnRH mRNA levels was detected in this strain. Likewise, in vivo gonadotropin responses to ovariectomy and systemic kisspeptin-10 or GnRH administration, as well as in vitro gonadotropin responses to GnRH, were fully preserved in SH rats. Moreover, circulating LH levels were grossly conserved during prepubertal maturation, whereas FSH levels were even enhanced from d 20 postpartum onwards. In striking contrast, ovarian weight and hormone (progesterone and testosterone) responses to human chorionic gonadotropin (CG) in vitro were profoundly decreased in SH rats, with impaired follicular development and delayed ovulation at puberty. Such reduced hormonal responses to human CG could not be attributed to changes in LH/CG or FSH-receptor mRNA expression but might be linked to blunted P450scc, 3beta-hydroxy steroid dehydrogenase, and aromatase mRNA levels in ovaries from SH rats. In conclusion, our results indicate that the expression and function of KiSS-1/GPR54 and GnRH/GnRH-receptor systems is normal in SH rats, whereas ovarian development, steroidogenesis, and responsiveness to gonadotropins are strongly compromised.

  20. A Case of Focal Small-cell Neuroendocrine Carcinoma in the Vicinity of the Extrahepatic Bile Duct, Adjacent to an Extensive Biliary Intraepithelial Neoplasm: A Diagnostic Challenge with Major Clinical Implications.

    Science.gov (United States)

    Aigner, Birgit; Kornprat, Peter; Schöllnast, Helmut; Kasparek, Anne-Katrin; Mischinger, Hans-Jörg; Haybaeck, Johannes

    2015-09-01

    Gastroenteropancreatic neuroendocrine tumors are known for their aggressiveness. Diagnosis of various bile duct pathologies, like biliar intraepithelial neoplasm, mixed adenoneuroendocrine carcinomas or small cell carcinomas, is challenging. This case report focuses on a rare case of a focal primary minute small cell carcinoma in the vicinity of the extrahepatic bile duct, presenting itself next to an extensive biliar intraepithelial neoplasm. This finding led to adjuvant chemotherapy, followed by major surgery. Therapeutic approach was based on CT and MRI scans but most importantly on immunohistochemistry and histological evaluation. Initially CR seemed achievable, but metastases were to be found rapidly. The authors want to underline the fact that major clinical decisions are based on sometimes tiny specimens; as literature shows it is absolutely advisable to use markers to differentiate the dignity of investigated areas. The authors call for keeping collision of tumors in mind and adding KOC staining and using it in a routine manner examining biliary duct lesions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. GnRH agonist for triggering of final oocyte maturation

    DEFF Research Database (Denmark)

    Al Humaidan, Peter Samir Heskjær; Kol, S; Papanikolaou, E G

    2011-01-01

    GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase...... deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering....

  2. Using GnRH to Improve Cow Fecundity after Calving

    Directory of Open Access Journals (Sweden)

    Nicolae Păcală

    2012-05-01

    Full Text Available At dairy cows, the increase in milk production is associated with the decrease of heat manifestation and conception rates. GnRH is mostly used for treatment of different problems of the reproductive function and for improving the pregnancy rates in cows. The aim of our paper was to contribute to increase of conception rates, at cows with ovarian activity, at first AI after calving. The experiments were conducted on 58 cows, from Romanian Black Spotted breed (Frezian and 53 cows from Romanian Spotted breed (Simmental. The animals were divided into lots as follows: for Romanian Black Spotted breed 33 of the cows in were in experimental lot and 25 were in control lot, for Romanian Spotted breed 29 ere in experimental lot and 24 were in control lot. The females form experimental lots were treated with 100 mcg (2ml Ovarelin (GnRH, at the first AI, after VWP. At the cows form Romanian Black Spotted, from the 33 females in experimental lot, 12 did not return into heat after insemination, which represents a conception rate of 36.4%. At the cows form Romanian Spotted, form the 29 cows in experimental lot 8 did not return into heat after insemination, representing a conception rate of 44.8%. Administration of 100 mcg GnRH (2 ml Ovarelin at the time of AI determines a significant increase of the conception rate with 8.4-11.5%, compared with control lot. It appears that the cows from Romanian Spotted reacts better at GnRH treatment (44.8% conception rate, compared with Romanian Black Spotted (36.4 % conception rate.

  3. A mathematical model for LH release in response to continuous and pulsatile exposure of gonadotrophs to GnRH

    Directory of Open Access Journals (Sweden)

    Reed Michael C

    2004-09-01

    Full Text Available Abstract In a previous study, a model was developed to investigate the release of luteinizing hormone (LH from pituitary cells in response to a short pulse of gonadotropin-releasing hormone (GnRH. The model included: binding of GnRH to its receptor (R, dimerization and internalization of the hormone receptor complex, interaction with a G protein, production of inositol 1,4,5-trisphosphate (IP3, release of calcium from the endoplasmic reticulum (ER, entrance of calcium into the cytosol via voltage gated membrane channels, pumping of calcium out of the cytosol via membrane and ER pumps, and release of LH. The extended model, presented in this paper, also includes the following physiologically important phenomena: desensitization of calcium channels; internalization of the dimerized receptors and recycling of some of the internalized receptors; an increase in Gq concentration near the plasma membrane in response to receptor dimerization; and basal rates of synthesis and degradation of the receptors. With suitable choices of the parameters, good agreement with a variety of experimental data of the LH release pattern in response to pulses of various durations, repetition rates, and concentrations of GnRH were obtained. The mathematical model allows us to assess the effects of internalization and desensitization on the shapes and time courses of LH response curves.

  4. Contemporary Incidence and Mortality Rates of Neuroendocrine Prostate Cancer.

    Science.gov (United States)

    Alanee, Shaheen; Moore, Aaron; Nutt, Max; Holland, Bradley; Dynda, Danuta; El-Zawahry, Ahmed; McVary, Kevin T

    2015-07-01

    The purpose of the study was to provide an update ever the incidence and mortality for neuroendocrine prostate cancer (NEPC) in the United States. Using a large national database, we examined changes in age-adjusted incidence (AAIR), mortality rates (MR) and 5-year cancer-specific survival (CSS) for 378 patients diagnosed with NEPC between 1992 and 2011. Analysis was performed for all NEPC and for its two major sub-groups [small cell carcinoma (SCC) and neuroendocrine carcinoma (NEC)]. AAIR of NEPC continues to rise in recent years (2004-2011:+6.8%/year, p>0.05). AAIR of SCC has been increasing significantly by 6.94%/year since 2001 (from 0.470 to 0.582/1,000,000 person years, pAAIR of SCC is increasing with no change in the MR of NEPC over the past 20 years. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Altered Neuroendocrine Immune Responses, a Two-Sword Weapon against Traumatic Inflammation.

    Science.gov (United States)

    Yang, Ce; Gao, Jie; Du, Juan; Yang, Xuetao; Jiang, Jianxin

    2017-01-01

    During the occurrence and development of injury (trauma, hemorrhagic shock, ischemia and hypoxia), the neuroendocrine and immune system act as a prominent navigation leader and possess an inter-system crosstalk between the reciprocal information dissemination. The fundamental reason that neuroendocrinology and immunology could mix each other and permeate toward the field of traumatology is owing to their same biological languages or chemical information molecules (hormones, neurotransmitters, neuropeptides, cytokines and their corresponding receptors) shared by the neuroendocrine and immune systems. The immune system is not only modulated by the neuroendocrine system, but also can modulate the biological functions of the neuroendocrine system. The interactive linkage of these three systems precipitates the complicated space-time patterns for the courses of traumatic inflammation. Recently, compelling evidence indicates that the network linkage pattern that initiating agents of neuroendocrine responses, regulatory elements of immune cells and effecter targets for immune regulatory molecules arouse the resistance mechanism disorders, which supplies the beneficial enlightenment for the diagnosis and therapy of traumatic complications from the view of translational medicine. Here we review the alternative protective and detrimental roles as well as possible mechanisms of the neuroendocrine immune responses in traumatic inflammation.

  6. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty.

    Science.gov (United States)

    Avendaño, M S; Vazquez, M J; Tena-Sempere, M

    2017-11-01

    Puberty is a complex developmental event, controlled by sophisticated regulatory networks that integrate peripheral and internal cues and impinge at the brain centers driving the reproductive axis. The tempo of puberty is genetically determined but is also sensitive to numerous modifiers, from metabolic and sex steroid signals to environmental factors. Recent epidemiological evidence suggests that the onset of puberty is advancing in humans, through as yet unknown mechanisms. In fact, while much knowledge has been gleaned recently on the mechanisms responsible for the control of mammalian puberty, fundamental questions regarding the intimate molecular and neuroendocrine pathways responsible for the precise timing of puberty and its deviations remain unsolved. By combining data from suitable model species and humans, we aim to provide a comprehensive summary of our current understanding of the neuroendocrine mechanisms governing puberty, with particular focus on its central regulatory pathways, underlying molecular basis and mechanisms for metabolic control. A comprehensive MEDLINE search of articles published mostly from 2003 to 2017 has been carried out. Data from cellular and animal models (including our own results) as well as clinical studies focusing on the pathophysiology of puberty in mammals were considered and cross-referenced with terms related with central neuroendocrine mechanisms, metabolic control and epigenetic/miRNA regulation. Studies conducted during the last decade have revealed the essential role of novel central neuroendocrine pathways in the control of puberty, with a prominent role of kisspeptins in the precise regulation of the pubertal activation of GnRH neurosecretory activity. In addition, different transmitters, including neurokinin-B (NKB) and, possibly, melanocortins, have been shown to interplay with kisspeptins in tuning puberty onset. Alike, recent studies have documented the role of epigenetic mechanisms, involving mainly

  8. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas

    DEFF Research Database (Denmark)

    Christensen, Lene Svendstrup; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    , a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers...... are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas....

  9. Involvement of glucocorticoids in testicular involution after active immunization of boars against GnRH.

    Science.gov (United States)

    Wagner, A; Claus, R

    2004-02-01

    Active GnRH immunization of boars inhibits LH and testicular steroids but the consequences for spermatogenesis are unknown. Six boars were immunized three times against GnRH at 20, 24 and 28 weeks. Another six boars served as controls. Plasma LH and FSH were determined at 28 and 31 weeks. Testosterone and cortisol were determined before killing the pigs at 32 weeks. Tissue samples were taken for histology and fluid from the seminiferous tubuli for steroid determination. Individual germ cells were counted in histological sections. The glucocorticoid receptor (GCR), mitosis of spermatogonia and apoptosis were characterized by immunocytochemistry. Immunization reduced LH and testosterone to base levels whereas FSH was not changed. Testis weight was reduced by 64% due to a loss of Leydig cell cytoplasm (90.3%) and a decrease of tubule diameters (60.6%). Except for A-spermatogonia, all other spermatogenic cells were reduced by about 60%. Mitosis was reduced in immunized boars. Expression of GCRs was limited to spermatogonia and differed between immunized boars (8% of spermatogonia) and controls (2%). In the controls, androgen concentrations in tubular fluid were tenfold higher compared with immunized boars. Cortisol concentrations were of the order of 40 nmol/l both in the tubular fluid and blood plasma. These concentrations did not differ between groups. Apoptosis occurred only in spermatogonia and pachytene spermatocytes and was twofold higher in immunized boars compared with controls. Thus the availability of glucocorticoids in the tubuli and the expression of GCRs initiate apoptosis, which in turn reduces sperm yield. Testosterone is known to be an inhibitor of GCR expression, thus increasing the efficiency of spermatogenesis.

  10. Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

    Directory of Open Access Journals (Sweden)

    Helga Bertani

    2011-01-01

    Full Text Available Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10% (1. Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2 cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2. Myasthenia gravis (MG is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR. MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3. No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour.

  11. Mucinous Carcinoma with Neuroendocrine Differentiation of Salivary Gland Origin.

    Science.gov (United States)

    Wong, Frankie K; Zumsteg, Zachary S; Langevin, Claude-Jean; Ali, Nabilah; Maclary, Shawn; Balzer, Bonnie L; Ho, Allen S

    2017-06-01

    Primary mucinous adenocarcinomas of the salivary gland are rare malignancies defined by aggregates of epithelial cells suspended in large pools of extracellular mucin. We report a case of a giant mucinous adenocarcinoma of salivary gland origin, with low-grade cytoarchitectural features and neuroendocrine differentiation arising in the submental region. Grossly, the tumor measured 12.5 × 13.4 × 8.2 cm and replaced the bone and soft tissues of the anterior oral cavity. Microscopically, the neoplasm was composed of large extracellular pools of mucin, which contained papillary and acinar aggregates, and small nodules of ductal type epithelium with minimal nuclear enlargement, powdery chromatin and little pleomorphism. The nodules comprised 20 % of the tumor and showed morphologic and immunohistochemical evidence of neuroendocrine differentiation. Examination revealed histologic features comparable to mammary gland analogues in mucin predominance, ductal type morphology, expression of estrogen and progesterone receptors, and GATA-3 positivity. This is the first case reported of mucin-rich carcinoma of salivary gland origin exhibiting neuroendocrine differentiation.

  12. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    -lymphocytes and natural killer cells are decreased with post-flight conditions. Of the lymphokines, interleukin-2 production, lymphocyte responsiveness, and the activity of natural killer cells are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest it is an effective simulation model for microgravity investigations. Neuroendocrine and pharmacological countermeasures are virtually nonexistent arid should become high priority items for future research. Although exercise has the potential to be an effective countermeasure for various neuroen-docrine-immune responses in microgravity, this concept must be tested before flights to Mars are scheduled.

  13. Minichromosome Maintenance Expression Defines Slow-Growing Gastroenteropancreatic Neuroendocrine Neoplasms

    Directory of Open Access Journals (Sweden)

    Simon Schimmack

    2016-10-01

    Full Text Available BACKGROUND: Small intestinal neuroendocrine neoplasm (SI-NEN proliferation is quantified by Ki67 measurements which capture G1-G2M phases of the cell cycle. G0 and early G1 phases, typical of slow-growing cells, can be detected by minichromosome maintenance protein (MCM expression. We hypothesized that these replication licensing markers may provide clinically relevant information to augment Ki67 in low-grade neuroendocrine neoplasia. METHODS: Immunohistochemical staining (IHC, Western blot analysis, quantitative polymerase chain reaction, and copy number variations of MCM2, MCM3, and Ki67 were undertaken in SI-NENs (n = 22. MCM and Ki67 expression was compared by Kaplan-Meier survival analysis (tissue microarray, independent set [n = 55]. Forty-three pancreatic NENs and 14 normal tissues were included as controls. RESULTS: In SI-NENs, MCM2 (mean: 21.2%: range: 16%-25% and MCM3 (28.7%: 22%-34% were detected in significantly more cells than Ki67 (2.3%: 0%-7%, P < .01. MCM2 mRNA correlated with Ki67 IHC (P < .05. MCM3 protein expression was higher in metastases (38-fold than in normal small intestine (P = .06 and was largely absent in normal neuroendocrine cells. There was considerable variation at the MCM copy number level (0-4 copies. MCM3 expression in proliferating cells significantly predicted overall survival (P < .002. Combinations of Ki67 and MCM2/3 in algorithms differentiated low and higher proliferative lesions (overall survival: 12 vs 6.1 years, P = .06. MCM expression was not informative in pancreatic NENs. CONCLUSION: MCMs are expressed in a higher proportion of NEN cells than Ki67 in slow-growing small intestinal lesions and correlate with survival. Assessment can be used to augment Ki67 to improve prognostic classification in these low-grade tumors.

  14. Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Engelund Luna, Iben; Monrad, Nina; Binderup, Tina

    2016-01-01

    OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological, and bio......OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological...

  15. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    OpenAIRE

    Todorović-Tirnanić Mila; Artiko Vera; Pavlović Smiljana; Šobić-Šaranović Dragana; Obradović Vladimir

    2015-01-01

    The new positron emission tomography (PET/CT) methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In-pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline a...

  16. Genetics of Isolated Hypogonadotropic Hypogonadism: Role of GnRH Receptor and Other Genes

    Directory of Open Access Journals (Sweden)

    Karges Beate

    2012-01-01

    Full Text Available Hypothalamic gonadotropin releasing hormone (GnRH is a key player in normal puberty and sexual development and function. Genetic causes of isolated hypogonadotropic hypogonadism (IHH have been identified during the recent years affecting the synthesis, secretion, or action of GnRH. Developmental defects of GnRH neurons and the olfactory bulb are associated with hyposmia, rarely associated with the clinical phenotypes of synkinesia, cleft palate, ear anomalies, or choanal atresia, and may be due to mutations of KAL1, FGFR1/FGF8, PROKR2/PROK2, or CHD7. Impaired GnRH secretion in normosmic patients with IHH may be caused by deficient hypothalamic GPR54/KISS1, TACR3/TAC3, and leptinR/leptin signalling or mutations within the GNRH1 gene itself. Normosmic IHH is predominantly caused by inactivating mutations in the pituitary GnRH receptor inducing GnRH resistance, while mutations of the β-subunits of LH or FSH are very rare. Inheritance of GnRH deficiency may be oligogenic, explaining variable phenotypes. Future research should identify additional genes involved in the complex network of normal and disturbed puberty and reproduction.

  17. The stimulation of testosterone and LH secretion by synthetic GnRH ...

    African Journals Online (AJOL)

    The effects of GnRH stimulation on plasma testosterone and luteinizing hormone (LH) levels in Cape porcupine males were examined by analysing plasma collected before and after an intravenous injection of GnRH. In six mature males and one subadult, which were given an intravenous injection of 0,5 ml saline, levels of ...

  18. Low-dose add-back therapy during postoperative GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  19. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics

    DEFF Research Database (Denmark)

    Muñoz, Manuel; Cruz, María; Humaidan, Peter

    2013-01-01

    OBJECTIVE: To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist+hCG triggering versus GnRH antagonist+GnRH agonist triggering) affect embryo development and kinetics. STUDY DESIGN: In a retrospective cohort study...

  20. Long-term effects of GnRH agonists on fertility and behaviour

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin

    2017-01-01

    This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin. Following an initial stimulation of gonadotropin and testosterone secretion...... possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour......; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option...

  1. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)

    1999-11-01

    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  2. Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Abbas Aflatoonian

    2017-08-01

    Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

  3. Primary Neuroendocrine Carcinoma of Ocular Adnexa

    Directory of Open Access Journals (Sweden)

    Daisuke Yamanouchi

    2013-01-01

    Full Text Available We present our findings in a case of primary neuroendocrine carcinoma (NEC of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

  4. Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature.

    Science.gov (United States)

    Angarita, Fernando A; Rodríguez, Jorge L; Meek, Eugenio; Sánchez, Jesus O; Tawil, Mauricio; Torregrosa, Lilian

    2013-06-05

    Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor. We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neoadjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis. The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.

  5. Lack of anti-androgenic effects of equol on reproductive neuroendocrine function in the adult male rat.

    Science.gov (United States)

    Loutchanwoot, Panida; Srivilai, Prayook; Jarry, Hubertus

    2014-01-01

    Equol (EQ), a metabolite of the soy isoflavone daidzein, has well known estrogenic properties. Data from animal studies suggested that EQ may act also as an anti-androgen. However, data regarding how EQ may affect brain functions like the regulation of neuroendocrine activity and reproductive outcomes in adult male rats are still lacking. We therefore investigated the effects of EQ on sex-steroid regulated gene expression in the brain [medial preoptic area/anterior hypothalamus (MPOA/AH) and medial basal hypothalamus/median eminence (MBH/ME)], pituitary, and prostate as a reference androgen-dependent organ. Furthermore reproductive outcomes were evaluated. The anti-androgen flutamide (FLUT) served as reference compound. Male rats (n=12 per group) were treated by gavage for 5 days with either EQ (100 or 250 mg/kgBW/day), or FLUT 100 mg/kgBW/day. All vehicle- and EQ-treated males showed successful reproductive outcomes, whereas FLUT-exposed males had severe reproductive impairments resulted in infertility. FLUT decreased relative weights of prostate, seminal vesicles and epididymides, and increased serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone and 5α-dihydrotestosterone without altering prolactin levels, whereas EQ exerted opposite effects. Both EQ and FLUT decreased gonadotropin releasing hormone (GnRH) expression in the MPOA/AH. Only FLUT upregulated levels of GnRH receptor expression both in the MBH/ME and pituitary. While EQ downregulated the hypothalamic ERα and ERβ expressions, but FLUT did not. In the prostate, only FLUT upregulated both ERα and AR mRNA expression levels. Taken together, our findings are the first data that EQ did not induce anti-androgenic effects on brain, prostate and male reproductive parameters, however, estrogenic neuroendocrine and reproductive effects of EQ were observed. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Assessment of functional changes in nanoparticle-exposed neuroendocrine cells with amperometry: exploring the generalizability of nanoparticle-vesicle matrix interactions.

    Science.gov (United States)

    Love, Sara A; Haynes, Christy L

    2010-09-01

    Using two of the most commonly synthesized noble metal nanoparticle preparations, citrate-reduced Au and Ag, the impacts of short-term accidental nanoparticle exposure are examined in primary culture murine adrenal medullary chromaffin cells. Transmission electron microscopy (TEM), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Alamar Blue viability studies revealed that nanoparticles are taken up by cells but do not decrease cell viability within 48 hours of exposure. Carbon-fiber microelectrode amperometry (CFMA) examination of exocytosis in nanoparticle-exposed cells revealed that nanoparticle exposure does lead to decreased secretion of chemical messenger molecules, of up to 32.5% at 48 hours of Au exposure. The kinetics of intravesicular species liberation also slows after nanoparticle exposure, between 30 and 50% for Au and Ag, respectively. Repeated stimulation of exocytosis demonstrated that these effects persisted during subsequent stimulations, meaning that nanoparticles do not interfere directly with the vesicle recycling machinery but also that cellular function is unable to recover following vesicle content expulsion. By comparing these trends with parallel studies done using mast cells, it is clear that similar exocytosis perturbations occur across cell types following noble metal nanoparticle exposure, supporting a generalizable effect of nanoparticle-vesicle interactions.

  7. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    Energy Technology Data Exchange (ETDEWEB)

    Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  8. Eel Kisspeptins: Identification, Functional Activity, and Inhibition on both Pituitary LH and GnRH Receptor Expression

    Directory of Open Access Journals (Sweden)

    Jérémy Pasquier

    2018-01-01

    Full Text Available The European eel (Anguilla anguilla presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. We previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of two Kiss genes. In the present study, we cloned and sequenced Kiss1 and Kiss2 cDNAs from the eel brain. The tissue distributions of Kiss1 and Kiss2 transcripts, as investigated by quantitative real-time PCR, showed that both genes are primarily expressed in the eel brain and pituitary. The two 10-residue long sequences characteristic of kisspeptin, eel Kp1(10 and Kp2(10, as well as two longer sequences, predicted as mature peptides, eel Kp1(15 and Kp2(12, were synthesized and functionally analyzed. Using rat Kiss1 receptor-transfected Chinese hamster ovary cells, we found that the four synthesized eel peptides were able to induce [Ca2+]i responses, indicating their ability to bind mammalian KissR-1 and to activate second messenger pathways. In primary culture of eel pituitary cells, all four peptides were able to specifically and dose-dependently inhibit lhβ expression, without any effect on fshβ, confirming our previous data with heterologous kisspeptins. Furthermore, in this eel in vitro system, all four peptides inhibited the expression of the type 2 GnRH receptor (gnrh-r2. Our data revealed a dual inhibitory effect of homologous kisspeptins on both pituitary lhβ and gnrh-r2 expression in the European eel.

  9. A fish model for the study of the relationship between neuroendocrine and immune cells in the intestinal epithelium: Silurus glanis infected with a tapeworm.

    Science.gov (United States)

    Dezfuli, B Sayyaf; DePasquale, J A; Castaldelli, G; Giari, L; Bosi, G

    2017-05-01

    Immunohistochemical, immunofluorescence and ultrastructural studies were conducted on a sub-population of 20 wels catfish Silurus glanis from a tributary of the River Po (Northern Italy). Fish were examined for the presence of ecto- and endo-parasites; in the intestine of 5 fish, 11 specimens of cestode Glanitaenia osculata were noted and was the only helminth species encountered. The architecture of intestine and its cellular features were nearly identical in either the uninfected S. glanis or in those harboring G. osculata. Near the site of worm's attachment, mucous cells, several mast cells (MCs), few neutrophils and some endocrine cells (ECs) were found to co-occur within the intestinal epithelium. MCs and neutrophils were abundant also in the submucosa. Immunohistochemical staining revealed that enteric ECs were immunoreactive to met-enkephalin, galanin and serotonin anti-bodies. The numbers of ECs, mucous cells and MCs were significantly higher in infected wels catfish (Mann-Whitney U test, p < 0.05). Dual immunofluorescence staining with the biotinylated lectin Sambucus nigra Agglutinin and the rabbit polyclonal anti-met-enkephalin or anti-serotonin, with parallel transmission electron microscopy, showed that ECs often made intimate contact with the mucous cells and epithelial MCs. The presence of numerous MCs in intestinal epithelium shows S. glanis to be an interesting model fish to study processes underlying intestinal inflammation elicited by an enteric worm. Immune cells, ECs and mucous cells of the intestinal epithelium have been described at the ultrastructural level and their possible functions and interactions together will be discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Dynamic evolution of the GnRH receptor gene family in vertebrates.

    Science.gov (United States)

    Williams, Barry L; Akazome, Yasuhisa; Oka, Yoshitaka; Eisthen, Heather L

    2014-10-25

    Elucidating the mechanisms underlying coevolution of ligands and receptors is an important challenge in molecular evolutionary biology. Peptide hormones and their receptors are excellent models for such efforts, given the relative ease of examining evolutionary changes in genes encoding for both molecules. Most vertebrates possess multiple genes for both the decapeptide gonadotropin releasing hormone (GnRH) and for the GnRH receptor. The evolutionary history of the receptor family, including ancestral copy number and timing of duplications and deletions, has been the subject of controversy. We report here for the first time sequences of three distinct GnRH receptor genes in salamanders (axolotls, Ambystoma mexicanum), which are orthologous to three GnRH receptors from ranid frogs. To understand the origin of these genes within the larger evolutionary context of the gene family, we performed phylogenetic analyses and probabilistic protein homology searches of GnRH receptor genes in vertebrates and their near relatives. Our analyses revealed four points that alter previous views about the evolution of the GnRH receptor gene family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans and previously presumed to be highly derived because it lacks the cytoplasmic C-terminal domain typical of most G-protein coupled receptors, is actually an ancient gene that originated in the common ancestor of jawed vertebrates (Gnathostomata). Second, unlike previous studies, we classify vertebrate GnRH receptors into five subfamilies. Third, the order of subfamily origins is the inverse of previous proposed models. Fourth, the number of GnRH receptor genes has been dynamic in vertebrates and their ancestors, with multiple duplications and losses. Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five

  11. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research.

    Science.gov (United States)

    Kockel, Lutz; Huq, Lutfi M; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E S; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E; Chisholm, Townley W; Kim, Seung K

    2016-10-13

    Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. Copyright © 2016 Kockel et al.

  12. A Drosophila LexA Enhancer-Trap Resource for Developmental Biology and Neuroendocrine Research

    Science.gov (United States)

    Kockel, Lutz; Huq, Lutfi M.; Ayyar, Anika; Herold, Emma; MacAlpine, Elle; Logan, Madeline; Savvides, Christina; Kim, Grace E. S.; Chen, Jiapei; Clark, Theresa; Duong, Trang; Fazel-Rezai, Vahid; Havey, Deanna; Han, Samuel; Jagadeesan, Ravi; Kim, Eun Soo Jackie; Lee, Diane; Lombardo, Kaelina; Piyale, Ida; Shi, Hansen; Stahr, Lydia; Tung, Dana; Tayvah, Uriel; Wang, Flora; Wang, Ja-Hon; Xiao, Sarah; Topper, Sydni M.; Park, Sangbin; Rotondo, Cheryl; Rankin, Anne E.; Chisholm, Townley W.; Kim, Seung K.

    2016-01-01

    Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila. However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals. PMID:27527793

  13. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol

    DEFF Research Database (Denmark)

    Toftager, M.; Bogstad, J; Bryndorf, T

    2016-01-01

    subjects who started gonadotrophin stimulation were included. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Δpp) = -3.8pp; 95% CI: -7.1 to -0.4; P = 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77...... gonadotrophin stimulation and per embryo transfer were all similar in the two groups. LIMITATIONS, REASONS FOR CAUTION: A possible limitation is the duration of the trial, with new methods, such as 'freeze all' and 'GnRH agonist triggering', being developed during the trial, the new methods were sought avoided......, however a total number of 32 women had 'freeze all' and 'GnRH agonist triggering' was performed in three cases. Ultrasonic measurements were performed by different physicians and inter-observer bias may be present. Measures of anti-Mullerian hormone and antral follicle count, to estimate ovarian reserve...

  14. Mucinous Carcinoma with Neuroendocrine Differentiation of Salivary Gland Origin

    OpenAIRE

    Wong, Frankie K.; Zumsteg, Zachary S.; Langevin, Claude-Jean; Ali, Nabilah; Maclary, Shawn; Balzer, Bonnie L.; Ho, Allen S.

    2016-01-01

    Primary mucinous adenocarcinomas of the salivary gland are rare malignancies defined by aggregates of epithelial cells suspended in large pools of extracellular mucin. We report a case of a giant mucinous adenocarcinoma of salivary gland origin, with low-grade cytoarchitectural features and neuroendocrine differentiation arising in the submental region. Grossly, the tumor measured 12.5 × 13.4 × 8.2 cm and replaced the bone and soft tissues of the anterior oral cavity. Microscopically, the neo...

  15. Changes in peripheral blood levels and pulse frequencies of GnRH in patients with hypopituitarism.

    Science.gov (United States)

    Hayashi, M; Takanashi, N; Yaoi, Y

    1998-09-01

    Pituitary dysfunction occasionally results from brain tumors or the surgical resection of brain tumors. The authors examined two patients with hypogonadotropic secondary amenorrhea, who had undergone surgical removal of brain tumors. Changes in immunoreactive gonadotropin-releasing hormone (GnRH) secretion are of interest in patients with a gonadotropin and gonadal steroid deficit, because both steroid and pituitary feedback systems are altered by tumors or tumor resection. The authors thus measured GnRH, luteinizing hormone, and follicle-stimulating hormone levels every 15 minutes for 4 hours by radioimmunoassay and investigated qualitative and quantitative changes in the pulsatile patterns of these hormones in two hypogonadotropic hypogonadism patients. They also performed similar multiple measurements of GnRH in two normal cycle women in follicular phase and two postmenopausal women. The concentration of plasma GnRH in two hypopituitarism patients was compared with that in two normal cycle women and two postmenopausal women. The study showed that the peripheral blood level of GnRH was significantly lower in two hypopituitarism patients than in both normal cycle and postmenopausal women, and that the pulsatile frequency was not different among these three groups. These findings suggest that alteration of feedback systems results in a decrease in the blood level of GnRH, and that pulses of GnRH maintain normal fluctuation despite the alteration of the hormonal circumstances in two hypogonadotropic hypogonadism patients.

  16. GnRH Protein Levels in Atrazine-Treated Axolotls (Ambystoma mexicanum

    Directory of Open Access Journals (Sweden)

    Sarah Leupen

    2008-01-01

    Full Text Available Atrazine is the most widely used agricultural herbicide in the United States and a known endocrine disruptor. In amphibians, it has been shown to cause gonadal malformations, feminization of males, behavioral changes, and immune suppression; however, its mechanism ofaction is unknown. We hypothesized that atrazine reduces the production of gonadotropin releasing hormone (GnRH in the hypothalamus. Axolotls (Ambystoma mexicanum were exposed to atrazine, 10-8 M ß-estradiol-3-benzoate, or no treatment and were sacrificed at 6, 8, and 10 months of age. GnRH neurons were labeled using immunocytochemistry, and labeled neurons were then counted using confocal microscopy. Although no significant difference wasfound in the total number of GnRH neurons, ectopic GnRH expression was seen in some brains. A significant negative correlation was found between presence of ectopic GnRH and number of normal GnRH neurons. Atrazine-treated animals were more likely than control or estrogentreated animals to have ectopic GnRH expression. The data implicate a central site of action of atrazine.

  17. Pulmonary neuroendocrine tumor in a female wolf (Canis lupus lupus).

    Science.gov (United States)

    Shiraki, Ayako; Yoshida, Toshinori; Kawashima, Masahi; Murayama, Hirotada; Nagahara, Rei; Ito, Nanao; Shibutani, Makoto

    2017-03-23

    A 17-year-old female wolf (Canis lupus lupus) had a right lung mass that was adhered to the thoracic cavity. Histopathological examination revealed that the mass consisted of sheets, cord or ribbon-like structures of monotonous, small, cuboidal cells with round, oval or short-spindle nuclei and scant clear cytoplasm, demarcated by a fine fibrovascular stroma. Focal necrosis, congestion and thrombi were observed. Immunohistochemically, the tumor cells diffusely expressed cytokeratin AE1/AE3, and some expressed chromogranin A, neural cell adhesion molecule (CD56) and thyroid transcription factor-1. The number of proliferating cell nuclear antigen-positive tumor cells was low. A diagnosis of pulmonary neuroendocrine tumor was based on the resemblance to carcinoids.

  18. DIABETES MELLITUS IN NEUROENDOCRINE DISEASES

    Directory of Open Access Journals (Sweden)

    I. V. Trigolosova

    2014-01-01

    early disability and death of patients with neuroendocrine diseases.

  19. Endoscopic diagnosis and treatment of neuroendocrine tumors of the digestive system

    Directory of Open Access Journals (Sweden)

    Sivero Luigi

    2016-01-01

    Full Text Available The authors evaluated the role of endoscopic techniques in the diagnosis and in the potential treatment of neuroendocrine tumors (NET localized in the gastro-entero-pancreatic system, on the basis of their experience and of the international literature. NET are rare tumors that arise from neuroendocrine cells of the gastrointestinal tract and pancreas. It is a possibility that both the digestive endoscopy and EUS play an important role in the diagnosis, staging and surveillance of this disease. In some cases, especially in the early stages, surgical endoscopy allows the treatment of such tumors.

  20. Primary neuroendocrine tumour of the breast: a case report and review of the literature.

    Science.gov (United States)

    Tato-Varela, Sara; Albalat-Fernández, Rosa; Pabón-Fernández, Sara; Zarco, Enrique Rodríguez; Calle-Marcos, Manolo La

    2015-01-01

    Primary neuroendocrine tumour of the breast is a rare entity that first appeared in the 2003 World Health Organisation (WHO) classification of breast tumours. The data currently available on its prognosis are contradictory, although it seems clear that histological varieties such as small cell neuroendocrine carcinoma have a worse prognosis, due to their low degree of differentiation. The treatment of choice is surgery, and the indications for chemotherapy or radiotherapy do not differ greatly from those used for other breast tumours. It is crucial to underline the difficulty of establishing treatment protocols due to the low incidence of this histological type.

  1. Incidental neuroendocrine tumor of the appendiceal base less ...

    African Journals Online (AJOL)

    Incidental neuroendocrine tumor of the appendiceal base less than20 mm in diameter: is appendectomy enough? Landolsi Sana, Mannai Saber. Abstract. The appendixis the second primary site for neuroendocrine tumors. The management of incidentelly discovered neuroendocrine tumor of the appendiceal base less ...

  2. Effect of reserpine on development and its neuro-endocrine regulation in Galleria mellonella

    DEFF Research Database (Denmark)

    Cymborowski, B.; Sørensen, Ilona Kryspin

    1975-01-01

    1. Studies were made on the effect of reserpine on development and its neuro-endocrine regulation in Galleria mellonella. It was shown that resperine greatly restricts the development of this insect. 2. Reserpine causes inhibition of the activity of the neurosecretory cells of pars intercerebralis...

  3. Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women.

    Science.gov (United States)

    Ronaldson, Amy; Gazali, Ahmad M; Zalli, Argita; Kaiser, Frank; Thompson, Stephen J; Henderson, Brian; Steptoe, Andrew; Carvalho, Livia

    2016-05-01

    The percentage of regulatory T cells (TRegs)-a subtype of T lymphocyte that suppresses the immune response-appears to be reduced in a number of stress-related diseases. The role of the TReg in stress-disease pathways has not yet been investigated. The aim of the study was to investigate the association between biological responsivity to acute psychosocial stress and the percentage of TRegs in healthy older adults. The secondary purpose was to measure the associations between TReg percentage and psychological and physical well-being in the participants. Salivary cortisol and plasma interleukin (IL)-6 samples were obtained from 121 healthy older men and women from the Whitehall II cohort following acute psychophysiological stress testing. Three years later at a follow-up visit, we measured TReg percentages and psychological and physical well-being were recorded using the Short Form 36 Health Survey and the Center for Epidemiologic Studies Depression Scale. Blunted cortisol responses (p = 0.004) and elevated IL-6 responses (p = 0.027) to acute psychophysiological stress were associated with greater TReg percentage independently of age, sex, BMI, smoking status, employment grade, time of testing, and baseline measures of cortisol and IL-6, respectively. Percentage of TRegs was associated cross-sectionally with lower physical (p = 0.043) and mental health status (p = 0.008), and higher levels of depressive symptoms (p = 0.002), independently of covariates. Increased levels of TRegs may act as a defence against increased inflammation and may be a pre-indication for chronically stressed individuals on the cusp of clinical illness.

  4. Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

    Science.gov (United States)

    Lipiński, Michał; Rydzewska, Grażyna; Foltyn, Wanda; Andrysiak-Mamos, Elżbieta; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Blicharz-Dorniak, Jolanta; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Falconi, Massimo; Handkiewicz-Junak, Daria; Hubalewska-Dydejczyk, Alicja; Jarząb, Barbara; Junik, Roman; Kajdaniuk, Dariusz; Kamiński, Grzegorz; Kolasińska-Ćwikła, Agnieszka; Kowalska, Aldona; Król, Robert; Królicki, Leszek; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Londzin-Olesik, Magdalena; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Poczkaj, Karolina; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; Starzyńska, Teresa; Steinhof-Radwańska, Katarzyna; Strzelczyk, Janusz; Sworczak, Krzysztof; Syrenicz, Anhelli; Szawłowski, Andrzej; Szczepkowski, Marek; Wachuła, Ewa; Zajęcki, Wojciech; Zemczak, Anna; Zgliczyński, Wojciech; Kos-Kudła, Beata

    2017-01-01

    This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.

  5. Irritable bowel syndrome: the role of gut neuroendocrine peptides.

    Science.gov (United States)

    El-Salhy, Magdy; Seim, Inge; Chopin, Lisa; Gundersen, Doris; Hatlebakk, Jan Gunnar; Hausken, Trygve

    2012-06-01

    Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 percent of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity.

  6. Mathematical modeling of the GnRH pulse and surge generator

    CERN Document Server

    Clement, Frederique

    2007-01-01

    We propose a mathematical model allowing for the alternating pulse and surge pattern of GnRH (Gonadotropin Releasing Hormone) secretion. The model is based on the coupling between two systems running on different time scales. The faster system corresponds to the average activity of GnRH neurons, while the slower one corresponds to the average activity of regulatory neurons. The analysis of the slow/fast dynamics exhibited within and between both systems allows to explain the different patterns (slow oscillations, fast oscillations and periodical surge) of GnRH secretion. Specifications on the model parameter values are derived from physiological knowledge in terms of amplitude, frequency and plateau length of oscillations. The behavior of the model is finally illustrated by numerical simulations reproducing natural ovarian cycles and either direct or indirect actions of ovarian steroids on GnRH secretion.

  7. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

    DEFF Research Database (Denmark)

    Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L

    2009-01-01

    in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

  8. Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology

    DEFF Research Database (Denmark)

    Stenbæk, D. S.; Toftager, M.; Hjordt, L. V.

    2015-01-01

    STUDY QUESTION: Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? SUMMARY ANSWER: ART treatment did not induce elevated levels...... of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. WHAT IS KNOWN ALREADY: ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological......-reported the Profile of Mood States, the Perceived Stress Scale, the Symptom Checklist-92-Revised, and the Major Depression Inventory questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up, and on the day of hCG testing. Also, a series of Profile of Mood States were reported daily during...

  9. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rinke, Anja, E-mail: sprengea@staff.uni-marburg.de; Michl, Patrick; Gress, Thomas [Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, Marburg D-35043 (Germany)

    2012-02-08

    Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-α, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  10. FDA Approves Lutathera for Neuroendocrine Tumors

    Science.gov (United States)

    FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

  11. A pancreatic neuroendocrine tumor diagnosed during the ...

    African Journals Online (AJOL)

    Pancreatic neuroendocrine tumors (PNET) are increasingly being discovered. A case of PNET diagnosed and treated during the management of acute appendicitis is presented and discussed. The importance of imaging modalities in patients with acute abdominal pain is emphasized. To the best our knowledge, this is the ...

  12. Nuclear Medicine Imaging of Neuroendocrine Tumors

    NARCIS (Netherlands)

    Brabander, Tessa; Kwekkeboom, Dik J.; Feelders, Richard A.; Brouwers, Adrienne H.; Teunissen, Jaap J. M.; Papotti, M; DeHerder, WW

    2015-01-01

    An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with In-111-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy

  13. Molecular neuroendocrine targets for obesity therapy.

    Science.gov (United States)

    de Kloet, Annette D; Woods, Stephen C

    2010-10-01

    Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy. During the review period, considerable progress occurred in the understanding of previously described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of the neuroendocrine regulation of energy homeostasis has been expanded. Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical-weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging.

  14. Other PET tracers for neuroendocrine tumors

    NARCIS (Netherlands)

    Koopmans, Klaas Pieter; Glaudemans, Andor W J M

    In this article the applicability of (124)I-MIBG and (11)C-5-HTP PET for the detection of abdominal gastro-enteropancreatic neuroendocrine tumors is discussed. (124)I-MIBG is a positron-emitting variant of (123)I-MIBG and therefore suited for PET imaging. Due to the better intrinsic characteristics

  15. Molecular neuroendocrine targets for obesity therapy

    Science.gov (United States)

    de Kloet, Annette D.; Woods, Stephen C.

    2013-01-01

    Purpose of review Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy. Recent findings During the review period, considerable progress occurred in the understanding of previously-described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of neuroendocrine regulators of energy homeostasis has been expanded. Summary Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging. PMID:20585249

  16. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Thomas Gress

    2012-02-01

    Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  17. Highly immunogenic and fully synthetic peptide-carrier constructs targetting GnRH

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Turkstra, J.A.

    1999-01-01

    using a tandem GnRH peptide as a branched polylysine construct, a lipo-thioester, a lipo-amide or a KLH conjugate in CFA, and the lipoamide peptide in an immuno-stimulating complex (ISCOM). We found the lipo-thioester and the branched polylysine constructs to be the most effective carrier molecules...... for the induction of antibodies against GnRH and immunocastration of pigs....

  18. Spaying-induced coat changes: the role of gonadotropins, GnRH and GnRH treatment on the hair cycle of female dogs.

    Science.gov (United States)

    Reichler, Iris Margaret; Welle, Monika; Eckrich, Christine; Sattler, Ursula; Barth, Andrea; Hubler, Madeleine; Nett-Mettler, Claudia S; Jöchle, Wolfgang; Arnold, Susi

    2008-04-01

    Although spaying can result in qualitative hair coat changes in dogs, the influence of spaying on the hair growth cycle has never been described. The study aims were to examine the effect of spaying and gonadotropin-releasing hormone (GnRH) treatment on canine hair coat, cycle stages of hair follicles, plasma gonadotropin concentrations and mRNA transcription of luteinizing hormone (LH) and GnRH receptors in hair follicles. Fifteen female dogs were examined before and 1 year after spaying and 24 spayed dogs before and after GnRH treatment. Spaying resulted in increased plasma gonadotropin concentrations and increased anagen : telogen ratio of hair follicles, but only 20% of the dogs developed coat changes. No differences were found in mRNA transcription of LH and GnRH receptors. GnRH treatment resulted in reduced plasma gonadotropin concentrations and improvement of coat changes in 79% of patients. This was associated with an increase in catagen hair follicles without changes in the anagen : telogen ratio. The present study demonstrated that spaying had an effect on the anagen : telogen ratio of hair follicles. Spaying-induced coat changes did not correlate with the anagen : telogen ratio. GnRH treatment reduced gonadotropin concentrations and reversed coat changes in some dogs, but had no effect on the hair growth cycle other than increasing the number of catagen hair follicles. A weak positive correlation between the plasma LH concentration and the anagen : telogen ratio was noted; however, our data did not suggest a direct receptor-mediated hormonal effect on the hair follicle. The present study did not identify the pathomechanism of spaying-induced coat changes.

  19. First-line treatment of patients with disseminated poorly differentiated neuroendocrine carcinomas with carboplatin, etoposide, and vincristine: a single institution experience

    DEFF Research Database (Denmark)

    Olsen, Ingrid Holst; Langer, Seppo W; Jepsen, Ida

    2012-01-01

    Poorly differentiated neuroendocrine carcinomas (PDECs) represent highly malignant tumors with an immense tendency to metastasize and with a poor prognosis. The treatment consists of palliative chemotherapy and corresponds to the treatment of extensive stage small cell lung cancer....

  20. Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders

    Directory of Open Access Journals (Sweden)

    Hemchand K Prasad

    2012-01-01

    Full Text Available Context: Gonadotrophin releasing hormone (GnRH stimulation test is pivotal in the assessment of children with pubertal disorders. However, lack of availability and high cost often result in the test falling into disfavor. We routinely use the GnRH analogue stimulation test as an alternative at our center. Aim: To present the data on children with endocrine disorders who underwent GnRH agonist stimulation test in pediatric endocrine clinic of a tertiary care referral hospital. Setting and Design: Pediatric endocrine clinic of a tertiary care referral hospital. Retrospective analysis of case records. Materials and Methods: The details pertaining to clinical and radiological parameters and hormonal tests were retrieved from case records of 15 children who underwent GnRH agonist stimulation test from May 2010 to April 2011. Results: Indications for testing with GnRH analogue were evaluation of delayed puberty, diagnosis of precocious puberty, assessment of hormonal suppression in treatment of precocious puberty and micropenis in two, nine, three and one cases, respectively. The results of the test and clinical and radiological parameters were in concordance. The test was also crucial in diagnosing the onset of central precocious puberty in two children with congenital adrenal hyperplasia. Conclusion: GnRH agonist test is a convenient, safe test that can be performed on an out-patient basis and can help the clinicians in the correct diagnosis and appropriate treatment of various puberty-related disorders.

  1. Reaction of cows ovaries to GnRH administration in different estrus cycle stages

    Directory of Open Access Journals (Sweden)

    Casiana Ciolac Șipețan

    2017-05-01

    Full Text Available Administration of GnRH in the luteal phase of estrous in dairy cows induces an increase of LH levels, with the modification of the growth waves of the ovarian follicles. GnRH induces ovulation or atresia of the dominant follicle and the recruitment of a new wave of follicular growth. The GnRH administration in the luteal phase of the estrous cycle induces growth waves synchronization of ovarian follicles, so that, a new wave of follicles started to grow at 5-6 days after administration. In our experiments, we administered 2ml Ovarelin (100 mcg GnRH, to three groups of cows (116 cows: in early luteal phase of the estrous cycle (days 4-5, in the middle of luteal phase (days 9-12, and late luteal phase (days 15-16. The rates of cows standing heat were 91.66% when GnRH was administered in early luteal phase, 95.22% when was administrated in the middle of luteal phase, and 73.68% in late luteal phase GnRH administration. After artificial insemination, the conception rates were 48.48% in early luteal phase, 52.5% at middle luteal phase and 46.42% in the late luteal phase of the estrous cycle.

  2. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Todorović-Tirnanić Mila

    2015-01-01

    Full Text Available The new positron emission tomography (PET/CT methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1 somatostatin analogues labeled with indium-111 (111In-pentetreotide or technetium-99m (99mTc-EDDA/HYNIC-TOC; 2 noradrenaline analogue labeled with iodine-131 or -123 (131I/123I-MIBG; or 3 99mTc(V-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F, galium-68 (68Ga, or carbon-11 (11C]: 1 glucose analogue (18FDG; 2 somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC; 3 aminoacid precursors of bioamines: [a dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine, b serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan]; or 4 dopamine analogue 18F-DA (6-18F-fluorodopamine. Conventional and contemporary (PET/ CT somatostatin receptor detection showed identical high specificity (92%, but conventional had very low sensitivity (52% compared to PET/CT (97%. It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic method. In metastatic pheochromocytoma detection contemporary (PET/ CT methods (18F-DOPA and 18F-DA have higher sensitivity than conventional (131I/123I-MIBG. In medullary thyroid carcinoma diagnostics contemporary method (18F-DOPA is more sensitive than conventional 99mTc(V-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET/CT methods for

  3. Stages of Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  4. Evidence for Changes in Numbers of Synaptic Inputs onto KNDy and GnRH Neurones during the Preovulatory LH Surge in the Ewe.

    Science.gov (United States)

    Merkley, C M; Coolen, L M; Goodman, R L; Lehman, M N

    2015-07-01

    Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto gonadotrophin-releasing hormone (GnRH) neurones. ARC kisspeptin cells that co-localise neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown in mice to also co-express the vesicular glutamate transporter, vGlut2, an established glutamatergic marker. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the the present study aimed to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, with the latter group killed at the time of the luteinising hormone (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to the luteal phase; because these did not contain kisspeptin, they do not arise from KNDy neurones. By contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in the mediobasal hypothalamus (MBH) was also increased during the LH surge, and could be attributed to an increase in the number of KNDy (double-labelled kisspeptin + vGlut2) inputs. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during

  5. Evidence for changes in numbers of synaptic inpcuts onto KNDy and GnRH neurones during the preovulatory LH surge in the ewe

    Science.gov (United States)

    Merkley, Christina M.; Coolen, Lique M.; Goodman, Robert L.; Lehman, Michael N.

    2016-01-01

    Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto GnRH neurones. ARC kisspeptin cells that co-localize neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown to also co-express the glutamatergic marker, vGlut2, in mice. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the goal of this study was to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, the latter group sacrificed at the time of the luteinising (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to luteal phase; as these did not contain kisspeptin they do not arise from KNDy neurons. In contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in both the POA and mediobasal hypothalamus was also increased during the LH surge. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during the ovine oestrous cycle, changes which may contribute to the generation of the preovulatory GnRH/LH surge. PMID:25976424

  6. Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology.

    Science.gov (United States)

    Stenbæk, D S; Toftager, M; Hjordt, L V; Jensen, P S; Holst, K K; Bryndorf, T; Holland, T; Bogstad, J; Pinborg, A; Hornnes, P; Frokjaer, V G

    2015-01-01

    Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? ART treatment did not induce elevated levels of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological characteristics, such as personality traits indexing negative emotionality, e.g. neuroticism, are likely to affect mental distress during ART treatment. A total of 83 women undergoing their first ART cycle were consecutively randomized 1:1 to GnRH antagonist (n = 42) or GnRH agonist (n = 41) protocol. The study population was a subgroup of a larger ongoing Danish clinical randomized trial and was established as an add-on in the period 2010-2012. Women in the GnRH antagonist protocol received daily injections with recombinant follicle-stimulating hormone, Puregon(®) and subcutaneous injections with GnRH antagonist, Orgalutran(®). Women in the GnRH agonist protocol received nasal administration of the GnRH agonist, Synarela(®) and subcutaneous injections with FSH, Puregon(®). The study design did not allow for a blinding procedure. All women self-reported the Profile of Mood States, the Perceived Stress Scale, the Symptom Checklist-92-Revised, and the Major Depression Inventory questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up, and on the day of hCG testing. Also, a series of Profile of Mood States were reported daily during pharmacological treatment to monitor mood fluctuations. The personality trait Neuroticism was assessed at baseline by the self-reported NEO-PI-R questionnaire. ART did not induce within- or between-protocol changes in any of the applied measures of mental distress. However, the GnRH

  7. Colonic neuroendocrine carcinoma in a child

    Energy Technology Data Exchange (ETDEWEB)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes [King Faisal Specialist Hospital and Research Centre, Department of Radiology, MBC 28, Riyadh (Saudi Arabia); Sathiapalan, Rajeev; Kofide, Amani [King Faisal Specialist Hospital and Research Centre, Department of Paediatric Haematology and Oncology, Riyadh (Saudi Arabia); Tulbah, Asthma Mahmoud Mohamed [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia); Al-Mehaidib, Ali [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia)

    2005-03-01

    A 10-year-old boy with congenital immunodeficiency (X-linked agammaglobulinaemia) presented with loss of appetite and weight, right-sided abdominal pain, diarrhoea and low-grade fever. Radiological investigations with barium follow-through, CT, PET and octreotide scans revealed a primary caecal/ascending proximal colonic mass with liver and bony metastases. Urine screen for 5HIAA was positive. Percutaneous liver biopsy confirmed the diagnosis of neuroendocrine carcinoma. The radiological work-up and the usefulness of various imaging modalities in the diagnosis of this rare paediatric tumour are discussed. The PET scan demonstrated the primary tumour and the metastatic locations more vividly than the octreotide scan, which is currently considered to be the most specific imaging modality for neuroendocrine masses. (orig.)

  8. Interventional treatment of neuroendocrine liver metastases

    DEFF Research Database (Denmark)

    Knigge, U.; Hansen, C.P.; Stadil, F.

    2008-01-01

    Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases s....... The symptomatic response rate is 90% with a mean duration of two years. Liver transplantation should be restricted to very few and highly selected patients without extrahepatic disease. Recurrence is inevitable in nearly all patients Udgivelsesdato: 2008/8......Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases...

  9. ART Outcomes in GnRH Antagonist Protocol (Flexible) and Long GnRH Agonist Protocol during Early Follicular Phase in Patients with Polycystic Ovary Syndrome: A Randomized Clinical Trial

    Science.gov (United States)

    Mokhtar, Sara; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Zafardoust, Simin; Badenush, Bita; Fatemi, Farnaz; Nazari, Fattane; Kamali, Koorosh; Mohammadzade, Afsaneh

    2015-01-01

    Background: Since increased LH in the early follicular phase in PCOS patients especially in GnRH antagonist protocol could be associated with reduced oocyte quality and pregnancy and impared implantation. The current study was conducted to determine ART outcomes in GnRH antagonist protocol (flexible) and long GnRH agonist protocol and compare them with adding GnRH antagonist in GnRH antagonist (flexible) protocol during early follicular phase in patients with polycystic ovary syndrome undergoing ICSI. Methods: In this randomized clinical trial, 150 patients with polycystic ovary syndrome undergoing ICSI were enrolled from 2012 to 2014 and randomly assigned to receive either GnRH antagonist protocol during early and late follicular phase or GnRH antagonist protocol (flexible) or long GnRH agonist protocol. The clinical and laboratory pregnancy in three groups was determined and compared. In this context, the chi-square and Fisher's exact test and ANOVA were used for data analysis. Statistical significance was defined as p<0.05. Results: There was no statistically significant difference with respect to chemical pregnancy and clinical pregnancy between the three groups. Also, other indices such as number and quality of oocytes and embryos were alike. Conclusion: Totally, according to our results, GnRH antagonist protocol during early and late follicular phase and GnRH antagonist protocol (flexible) and long GnRH agonist protocol in patients with polycystic ovary syndrome undergoing ICSI are similarly effective and use of each one based on patients' condition and physicians' opinion could be considered. PMID:26913233

  10. Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast.

    Science.gov (United States)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-07-01

    Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity added by WHO in 2003. Since then, studies have indicated that NCB potentially displays a worse prognosis than invasive ductal carcinoma. However, due to a lack of standard use of immunohistochemical staining for neuroendocrine markers and the fact that NCB may only show slight neuroendocrine morphology that can easily be overlooked, NCB is often underdiagnosed. Consequently, there is a need for fast and reliable detection method for NCB. Here, we take a first step toward finding an easy way of identifying NCB by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained for the neuroendocrine markers chromogranin A and synaptophysin. Cases positive in more than 50% of the tumor cells were accepted in accordance with WHO (2003) standards of NCB. Sensitivity and specificity for TMA sections vs whole-mount sections were found to be 100% and 97.8%, respectively, suggesting that TMA analysis is a reliable method for NCB detection. © 2013 APMIS. Published by John Wiley & Sons Ltd.

  11. [Surgical approach of gastroduodenal neuroendocrine neoplasms].

    Science.gov (United States)

    Fendrich, V; Bartsch, D K

    2016-04-01

    Gastroduodenal neuroendocrine tumors are rare but an increase in incidence has been recognized worldwide over the past 35 years. At the same time the prognosis of patients has substantially improved because the majority of these tumors can now be detected at an early stage. Neuroendocrine neoplasms (NENs) of the stomach are the most frequent neoplasms of neuroendocrine origin in the gastrointestinal tract. The therapeutic management of these tumors is complicated by the fact that they must be classified not only by staging and grading but also according to their pathophysiological background (types). These types differ in biological behavior and therefore have an influence on the therapeutic concept. Because more than 90 % of duodenal NENs are often asymptomatic and are as a rule identified at a curable stage, resection of the tumor should always be the first line of therapy. The therapeutic strategies vary from local endoscopic resection (duodenotomy with excision) up to pancreas retaining duodenectomy and pylorus retaining or classical Whipple procedures. This article presents the various surgical approaches to gastric and duodenal NENs.

  12. Reproductive disturbances in multiple neuroendocrine tumor syndromes.

    Science.gov (United States)

    Lytras, Aristides; Tolis, George

    2009-12-01

    In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

  13. ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs

    Directory of Open Access Journals (Sweden)

    Mark D. Borromeo

    2016-08-01

    Full Text Available Small cell lung carcinoma (SCLC is a high-grade pulmonary neuroendocrine tumor. The transcription factors ASCL1 and NEUROD1 play crucial roles in promoting malignant behavior and survival of human SCLC cell lines. Here, we find that ASCL1 and NEUROD1 identify heterogeneity in SCLC, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, and NFIB while NEUROD1 targets MYC. ASCL1 and NEUROD1 regulate different genes that commonly contribute to neuronal function. ASCL1 also regulates multiple genes in the NOTCH pathway including DLL3. Together, ASCL1 and NEUROD1 distinguish heterogeneity in SCLC with distinct genomic landscapes and distinct gene expression programs.

  14. The many faces of neuroendocrine differentiation in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Stephane eTerry

    2014-03-01

    Full Text Available In normal prostate, neuroendocrine (NE cells are rare and interspersed among the epithelium. These cells are believed to provide trophic signals to epithelial cell populations through the secretion of an abundance of neuropeptides that can diffuse to influence surrounding cells. In the setting of prostate cancer (PC, NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but in some cases adenocarcinoma cells themselves acquire NE characteristics. This epithelial plasticity is associated with decreased androgen receptor (AR signaling and the accumulation of neuronal and stem cell characteristics. Transformation to a NE phenotype is one proposed mechanism of resistance to contemporary AR targeted treatments, is associated with poor prognosis, and thought to represent up to 25% of lethal PCs. Importantly, the advent of high-throughput technologies has started to provide clues for understanding the complex molecular profiles of tumors exhibiting NE differentiation. Here, we discuss these recent advances, the multifaceted manner by which a NE-like state may arise during the different stages of disease progression, and the potential benefit of this knowledge for the management of patients with advanced PC

  15. Morinda Officinalis Polysaccharides Stimulate Hypothalamic GnRH Secretion in Varicocele Progression

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2017-01-01

    Full Text Available Varicoceles (VCs are the predominant cause of male infertility and are a risk factor for chronic venous disease. Morinda officinalis (M. officinalis is a traditional Chinese medicine used to tonify the kidney and strengthen yang. In this study, we evaluated the effects of water-soluble polysaccharides extracted from M. officinalis (MOPs on gonadotropin-release hormone (GnRH secretion in a classic experimental left VC (ELV rat model. Intragastric administration of MOPs at a dose ranging from 50 mg kg−1 to 100 mg kg−1 facilitated improvements in sperm parameters and seminiferous epithelial structures, modulated serum hormone profiles, and stimulated GnRH synthesis and release in the hypothalamus. MOPs also promoted spinogenesis and functional spine maturation in the arcuate nuclei (Arc, wherein they acted mainly on Kiss1 and GnRH neurons. Moreover, MOP-mediated Kisspeptin-GPR54 pathway upregulation and MAPK phosphorylation activation may have been responsible for increases in GnRH synthesis and release. Collectively, the findings of this study indicate that MOPs were effective in stimulating GnRH secretion, possibly by upregulating the Kiss1/GPR54 pathway and enhancing synaptic plasticity, and that MOPs can serve as a therapy for early VCs.

  16. Evolution of vertebrate GnRH receptors from the perspective of a basal vertebrate

    Directory of Open Access Journals (Sweden)

    Stacia A Sower

    2012-11-01

    Full Text Available This minireview provides the current status on gonadotropin-releasing hormone receptors (GnRH-R in vertebrates, from the perspective of a basal vertebrate, the sea lamprey, and provides an evolutionary scheme based on the recent advance of whole genome sequencing. In addition, we provide a perspective on the functional divergence and evolution of the receptors. In this review we use the phylogenetic classification of vertebrate GnRH receptors that groups them into three clusters: type I (mammalian and non-mammalian, type II, and type III GnRH receptors. New findings show that the sea lamprey has two type III-like GnRH receptors and an ancestral type GnRH receptor that is more closely related to the type II-like receptors. These two novel GnRH receptors along with lGnRH-R-1 share similar structural features and amino acid motifs common to other known gnathostome type II/III receptors. Recent data analyses of the lamprey genome provide strong evidence that 2 whole rounds of genome duplication (2R occurred prior to the gnathostome-agnathan split. Based on our current knowledge, it is proposed that lGnRH-R-1 evolved from an ancestor of the type II receptor following a vertebrate-shared genome duplication and that the two type III receptors resulted from a duplication within lamprey of a gene derived from a lineage shared by many vertebrates.

  17. Combined ovulation triggering with GnRH agonist and hCG in IVF patients.

    Science.gov (United States)

    Kasum, Miro; Kurdija, Kristijan; Orešković, Slavko; Čehić, Ermin; Pavičić-Baldani, Dinka; Škrgatić, Lana

    2016-11-01

    The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation.

  18. Photoperiod-independent changes in immunoreactive brain gonadotropin-releasing hormone (GnRH) in a free-living, tropical bird.

    Science.gov (United States)

    Moore, Ignacio T; Bentley, George E; Wotus, Cheryl; Wingfield, John C

    2006-01-01

    Timing of seasonal reproduction in high latitude vertebrates is generally regulated by photoperiodic cues. Increasing day length in the spring is associated with changes in the brain that are responsible for mediating reproductive activities. A primary example of this is the increased content of gonadotropin-releasing hormone (GnRH) in the preoptic area of the hypothalamus in birds as they enter the spring breeding season. Increased GnRH activity stimulates the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. These gonadotropins induce growth of the gonads and release of sex steroids which act on the brain to mediate reproductive behaviors. By contrast, seasonal breeding in the tropics can occur in the absence of significant changes in photoperiod. To our knowledge, no studies have investigated whether seasonal breeding in free-living tropical vertebrates is associated with seasonal changes in the GnRH system. We studied two populations of rufous-collared sparrows (Zonotrichia capensis) at the equator, separated by only 25 km, but with asynchronous reproductive phenologies associated with local climate and independent of photoperiodic cues. We collected brains and measured GnRH immunoreactivity (GnRH-ir) during each population's breeding and non-breeding periods. Breeding males had larger, but not more, GnRH-ir cells than non-breeding birds. The plasticity of the GnRH system was associated with local climate, such that the two populations exhibited asynchronous changes in GnRH-ir despite experiencing identical photoperiod conditions. Our results demonstrate that tropical birds can exhibit neural changes similar to those exhibited in higher latitude birds. However, these tropical populations appear to be using supplementary cues (e.g., rainfall, temperature, food availability) in a similar way to higher latitude species using an initial predictive cue (photoperiod). These results raise questions about the evolution of

  19. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist

    DEFF Research Database (Denmark)

    Humaidan, P; Bungum, L; Bungum, M

    2006-01-01

    Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to determine the clinical and endocrine effects as well the optimal timing of HCG supplementation. Forty-five normogonadotrophic IVF/ICSI p...

  20. [Advances of circulating biomarkers in gastroenteropancreatic neuroendocrine neoplasms].

    Science.gov (United States)

    Chen, Luohai; Chen, Minhu; Chen, Jie

    2017-03-25

    Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.

  1. Neuroendocrine Tumour of the Prostate: A Rare Variant

    Directory of Open Access Journals (Sweden)

    Ozer Ural Cakici

    2013-12-01

    Full Text Available About 95% of prostate cancers are adenocarcinomas. Neuroendocrine differentiation (NED is seen in virtually all cases of prostatic carcinoma, mostly in a focal pattern. Extensive NED is associated to aggressive disease with a poor prognosis and most cases are diagnosed in advanced stages.We present a 79-year- old male who was admitted to our department with severe lower urinary tract obstructive symptoms and weight loss. On digital rectal examination, the prostate was fixed to the rectum with irregular margins. Serum prostate-specific antigen (PSA level was 1.9 ng/ml.Transrectal ultrasound-guided prostate biopsies revealed small-cell carcinoma of the prostate. Multiple metastatic lesions in vertebral bones and iliac lymph nodes were detected by nuclear bone scan and abdominal computerised tomography CT. Thereafter, the patient was treated with cisplatin-based chemotherapy and palliative radiotherapy.

  2. Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

    DEFF Research Database (Denmark)

    Juul, A; Müller, J; Skakkebaek, N E

    1997-01-01

    In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific...... antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with Gn......RH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys....

  3. Immunohistochemical detection of dopamine D2 receptors in neuroendocrine tumours.

    Science.gov (United States)

    Pawlikowski, Marek; Pisarek, Hanna; Winczyk, Katarzyna

    2011-01-01

    Recently, dopamine D2 receptors (RD2) have been found to be expressed in neuroendocrine tumours (NET), the tumours which arise from the diffuse neuroendocrine cells. Moreover, successful trials of the treatment of NET with cabergoline - D2 agonist, have been reported. These findings increase the interest of investigating RD2 expression in NET. The expression of RD2 was investigated immunohistochemically using the antibody which recognises both short (S) and long (L) isoforms of the receptor in 17 NET samples taken from 15 patients. In 17 NET samples, a positive reaction with the anti-RD2 antibody occurred in 11 cases. In six cases, the localisation of the immunostaining was cytoplasmic and in nine cases it was nuclear. Only in one case was the receptor cell membrane-located, and in two cases the immunoreaction was also localised in the blood vessels walls. The relation between RD2 expression and the grade of malignancy examined by means of Ki-67 antigen expression needs further study. However, preliminary observations indicate that the nuclear localisation of RD2 is linked to higher tumour malignancy. The next investigated question was the co-expression of somatostatin and dopamine receptors. This question seems important because of the perspectives of somatostatin-dopamine chimeras application in NET treatment. In the samples examined by us, RD2 were co-expressed in 5/10 cases with sstr1, in 3/10 with sstr2A, in 2/9 with sstr2B, in 3/10 with sstr3, and in 5/10 with sstr5. Dopamine D2 receptors are revealed by means of immunohistochemistry in the majority of NET. They exhibit cytoplasmic and/or nuclear localisations, the latter being possibly linked to a higher grade of malignancy, and are often co-expressed with somatostatin receptors (mostly with subtypes1 and 5).

  4. Neuronal-glial plasticity in gonadotropin-releasing hormone release in adult female rats: role of the polysialylated form of the neural cell adhesion molecule.

    Science.gov (United States)

    Parkash, Jyoti; Kaur, Gurcharan

    2005-08-01

    The gonadotropin-releasing hormone (GnRH) neurosecretory system undergoes marked structural and functional changes during the ovarian cycle. The aim of this study was to examine the neuroanatomical relationship between GnRH neurons and a polysialylated form of neural cell adhesion molecule (PSA-NCAM), a known marker of neuronal plasticity. Using immunohistofluorescent dual labeling, we determined that axon terminals of GnRH in the median arcuate nucleus (ME-ARC) region of the hypothalamus in the proestrous phase of the estrous cycle were intimately associated with PSA-NCAM. To further examine whether PSA-NCAM expression associated with GnRH neuron terminals varies in conjugation with cyclic changes in ovarian steroid hormone levels, we examined GnRH and PSA-NCAM dual expression in ovariectomized (OVX) and estrogen-progesterone-primed OVX (EBP-OVX) rats. The expression of PSA-NCAM immunoreactivity associated with the GnRH neurons in the proestrous phase and EBP-OVX rats was significantly higher than during the diestrous phase and in OVX rats where GnRH secretion declines. We further examined whether the structural changes in GnRH axon terminals in the ME-ARC region are also associated with glial plasticity. By extension and retraction of the glial processes, the GnRH neuron terminals in the ME-ARC region could undergo dynamic plastic changes that control GnRH release during the proestrous phase. PSA-NCAM expression was also seen on glial cells in the ME-ARC region. The close association between PSA-NCAM on GnRH and glial cells in the ME-ARC region of the hypothalamus in the rat showed dynamic structural changes in GnRH neuron terminals during the estrous cycle. These observations suggested that PSA-NCAM may act as a molecular substrate to promote neuroplastic changes in the GnRH neurosecretory system.

  5. Long-term effects of GnRH agonists on fertility and behaviour.

    Science.gov (United States)

    Goericke-Pesch, S

    2017-04-01

    This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin. Following an initial stimulation of gonadotropin and testosterone secretion possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option to predict castration-related effects on behaviour and to identify animals where surgical castration will not be beneficial. No effect has been seen in reducing aggression towards humans indicating the need for behavioural therapy to control this problem. Effects on spermatogenesis, steroidogenesis and behaviour have by now been shown to be fully reversible. Knowledge in females is more limited, and particularly, the initial induction of a possibly fertile oestrus and individual variation in duration of efficacy remain problems in bitches and queens treated for suppression of fertility. However, long-term suppression of oestrous cycle and fertility seems to be possible with induced effects shown to be reversible including restoration of normal fertility after the end of efficacy/GNRH A-SRI removal. © 2016 Blackwell Verlag GmbH.

  6. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  7. Common Diagnostic Challenges in the Histopathologic Diagnosis of Neuroendocrine Lung Tumors: A Case Report

    Directory of Open Access Journals (Sweden)

    Monica Valente

    2010-07-01

    Full Text Available Bronchopulmonary neuroendocrine tumors are an uncommon group of neoplasms, accounting for about 20% of all lung carcinomas, arising from stem cells of the bronchial epithelium known as Kulchitsky cells. In the past, these tumors were grouped among benign or less aggressive malignant pulmonary tumors. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade (typical carcinoid; TC, intermediate-grade (atypical carcinoid; AC and high-grade (large-cell neuroendocrine carcinoma, LCNEC, and small-cell lung carcinoma, SCLC. They differ by morphologic, immunohistochemical and structural features. At histopathologic analysis, these tumors share progressive increase in a number of mitotic figures per 10 high-power fields and in the extent of necrosis, with TC having the lowest values and SCLC having the highest. TCs and ACs make up approximately 1–2% of all primary lung tumors. Differentiating ACs from TCs or LCNEC and SCLC is clinically important because the treatment modalities and prognoses for these types of tumors are different. We report a case of misdiagnosis of bronchopulmonary neuroendocrine tumor in a young woman which has heavily influenced her clinical history.

  8. The effects of a slow release GnRH agonist implant on male rabbits

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Groeger, Gesa; Wehrend, Axel

    2015-01-01

    . Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant...... in SG and not different from CG. Application of a slow release GnRH agonist implant does not induce hormonal castration in male rabbits over a period of 90 days indicating that it is not a suitable alternative to surgical castration in this species....

  9. Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations.

    Directory of Open Access Journals (Sweden)

    Bruno Francou

    Full Text Available CONTEXT: TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH (OMIM #146110. In the absence of animal models, studies of human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher the pathophysiology of this signaling pathway. OBJECTIVE: To evaluate the prevalence of TAC3/TACR3 mutations, characterize novel TACR3 mutations and to analyze neuroendocrine profiles in nCHH caused by deleterious TAC3/TACR3 biallelic mutations. RESULTS: From a cohort of 352 CHH, we selected 173 nCHH patients and identified nine patients carrying TAC3 or TACR3 variants (5.2%. We describe here 7 of these TACR3 variants (1 frameshift and 2 nonsense deleterious mutations and 4 missense variants found in 5 subjects. Modeling and functional studies of the latter demonstrated the deleterious consequence of one missense mutation (Tyr267Asn probably caused by the misfolding of the mutated NK3R protein. We found a statistically significant (p<0.0001 higher mean FSH/LH ratio in 11 nCHH patients with TAC3/TACR3 biallelic mutations than in 47 nCHH patients with either biallelic mutations in KISS1R, GNRHR, or with no identified mutations and than in 50 Kallmann patients with mutations in KAL1, FGFR1 or PROK2/PROKR2. Three patients with TAC3/TACR3 biallelic mutations had an apulsatile LH profile but low-frequency alpha-subunit pulses. Pulsatile GnRH administration increased alpha-subunit pulsatile frequency and reduced the FSH/LH ratio. CONCLUSION: The gonadotropin axis dysfunction associated with nCHH due to TAC3/TACR3 mutations is related to a low GnRH pulsatile frequency leading to a low frequency of alpha-subunit pulses and to an elevated FSH/LH ratio. This ratio might be useful for pre-screening nCHH patients for TAC3/TACR3 mutations.

  10. Neuroendocrine tumour in a patient with neurofibromatosis type 1 ...

    African Journals Online (AJOL)

    2015-06-26

    Jun 26, 2015 ... concomitant gastrin-producing neuroendocrine tumour was found. Neuroendocrine tumours. (NETs) are very rare neoplasms originating from a wide variety of endocrine and nervous system tissue with the ability to produce different hormones. A somatostatin- and gastrin- secreting NET in a patient with HIV ...

  11. Recognition memory tasks in neuroendocrine research.

    Science.gov (United States)

    Luine, Victoria

    2015-05-15

    The recognition memory tasks, novel object and novel object location, have been beneficial to neuroendocrine research concerning the effects of gonadal and adrenal hormones on cognitive function. This review discusses the advantages of these tasks in comparison with other learning and memory tasks. Experiments conducted across a number of laboratories show that gonadal hormones, both estradiol and testosterone, promote memory while the adrenal hormone, corticosterone, impairs memory. The effects of these steroid hormones on spine density in the prefrontal cortex and hippocampus are also briefly presented. Overall, results show that these steroid hormones are potent modulators of memory consolidation in rodent models. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system.

    Science.gov (United States)

    Morale, M C; Gallo, F; Tirolo, C; Testa, N; Caniglia, S; Marletta, N; Spina-Purrello, V; Avola, R; Caucci, F; Tomasi, P; Delitala, G; Barden, N; Marchetti, B

    2001-08-01

    Bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life. Signals generated by the hypothalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the development of immune system function. Conversely, products generated by immune system activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to preperinatal experiences, including hormonal manipulations and immune challenges, which may influence the future predisposition to several disease entities. We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the central nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate major changes in response to hormonal manipulations and pro-inflammatory triggers. The interplay between LHRH, sex steroids, GC and pro-inflammatory mediators in some physiological and pathological states, together with the potential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmacological targeting with drugs acting at the neuroendocrine-immune interface.

  13. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects

    DEFF Research Database (Denmark)

    Zhu, Xiaorong; Zhou, An; Dey, Arunangsu

    2002-01-01

    The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway. They are expressed together or separately in neuroendocrine cells throughout the brain and dispersed endocrine system in both ...

  14. Dissociative symptoms and neuroendocrine dysregulation in depression.

    Science.gov (United States)

    Bob, Petr; Fedor-Freybergh, Peter; Jasova, Denisa; Bizik, Gustav; Susta, Marek; Pavlat, Josef; Zima, Tomas; Benakova, Hana; Raboch, Jiri

    2008-10-01

    Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.

  15. A novel approach in the treatment of neuroendocrine gastrointestinal tumors: Additive antiproliferative effects of interferon-γ and meta-iodobenzylguanidine

    Directory of Open Access Journals (Sweden)

    Ahnert-Hilger Gudrun

    2004-05-01

    Full Text Available Abstract Background Therapeutic options to effectively inhibit growth and spread of neuroendocrine gastrointestinal tumors are still limited. As both meta-iodobenzylguanidine (MIBG and interferon-γ (IFNγ cause antineoplastic effects in neuroendocrine gastrointestinal tumor cells, we investigated the antiproliferative effects of the combination of IFNγ and non-radiolabeled MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells. Methods and results IFNγ receptors were expressed in both models. IFNγ dose- and time-dependently inhibited the growth of both STC-1 and of BON tumor cells with IC50-values of 95 ± 15 U/ml and 135 ± 10 U/ml, respectively. Above 10 U/ml IFNγ induced apoptosis-specific caspase-3 activity in a time-dependent manner in either cell line and caused a dose-dependent arrest in the S-phase of the cell cycle. Furthermore, IFNγ induced cytotoxic effects in NE tumor cells. The NE tumor-targeted drug MIBG is selectively taken up via norepinephrine transporters, thereby specifically inhibiting growth in NE tumor cells. Intriguingly, IFNγ treatment induced an upregulation of norepinephrine transporter expression in neuroendocrine tumors cells, as determined by semi-quantitative RT-PCR. Co-application of sub-IC50 concentrations of IFNγ and MIBG led to additive growth inhibitory effects, which were mainly due to increased cytotoxicity and S-phase arrest of the cell cycle. Conclusion Our data show that IFNγ exerts antiproliferative effects on neuroendocrine gastrointestinal tumor cells by inducing cell cycle arrest, apoptosis and cytotoxicity. The combination of IFNγ with the NE tumor-targeted agent MIBG leads to effective growth control at reduced doses of either drug. Thus, the administration of IFNγ alone and more so, in combination with MIBG, is a promising novel approach in the treatment of neuroendocrine gastrointestinal tumors.

  16. Effect of gonadotropin-releasing hormone (GnRH) treatment on ...

    African Journals Online (AJOL)

    Administrator

    2011-09-28

    Sep 28, 2011 ... 1169-1171. Eppleston J, Roberts EM (1991). Effect of time of PMSG and GnRH on the time of ovulation, LH secretion and reproductive performance after intrauterine insemination with frozen ram semen. Anim. Reprod. Sci. 26: 227-237. Evans NP, Dahl GE, Caraty A, Padmanabhan V, Thrun LA, Karsch FJ.

  17. Is the use of a GnRH antagonist effective in patients with polycystic ...

    African Journals Online (AJOL)

    offered controlled ovarian stimulation (COS) and in vitro fertilisation (IVF) technology. Aim. The aim of this study was to assess whether there was a difference in the pregnancy outcomes of women with PCOS when a standard gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) protocol was used for ovarian ...

  18. Superovulatory response in Boer goats pre-treated with a GnRH ...

    African Journals Online (AJOL)

    The aim of this study was to evaluate the ovarian response and embryo recovery rates in Boer goat does superovulated with pFSH following a pre-treatment with a GnRH agonist (GnRHa) outside the natural breeding season. Oestrus was synchronised in 22 does with CIDR\\'s for 17 days, and these were superovulated with ...

  19. Hormonal responses to GnRH injection given at different stages of ...

    African Journals Online (AJOL)

    The objective of the present study was to evaluate the hormonal responses of buffaloes to GnRH injections given at different moments of the estrous cycle. The estrous cycles of 15 buffaloes were synchronized with 2 im injections of prostaglandin F2α given 11 days apart. The buffalos were randomly assigned to 1 of 3 ...

  20. Effect of gonadotropin-releasing hormone (GnRH) treatment on ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of gonadotropin-releasing hormone (GnRH) administration on the induction of multiple births in synchronized Afshari ewes. 16 cycling, multiparous fat-tailed Iranian Afshari ewes, weighing 66.5 ± 2.5 kg, were used in the trail. Estrus was synchronized using controlled ...

  1. EFFECT TN EWES OF OESTROGEN PRIMING AND GnRH ON LH ...

    African Journals Online (AJOL)

    EFFECT TN EWES OF OESTROGEN PRIMING AND GnRH ON LH RELEASE. AND LUTEAL FUNCTION DURING EARLY LACTATION IN SPRING. Receipt of MS 22-03-1979. C.D. Hamilton*, A.W. Lishman and P.A. Lamb. Department ol Animal Science, Universitlt ol'Natol, nercrmaitzburg, 3200. (Key words. Oestrogen ...

  2. Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

    Directory of Open Access Journals (Sweden)

    Takayoshi eUbuka

    2013-03-01

    Full Text Available Seasonally breeding birds detect environmental signals, such as light, temperature, food availability and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH, activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH, inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction.

  3. A NEW INCOME IN PEDIATRIC PATHOLOGY: GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS. PART I: PANCREATIC TUMORS

    Directory of Open Access Journals (Sweden)

    Smaranda DIACONESCU

    2013-03-01

    Full Text Available Gastroenteropancreatic neuroendocrine tumors (GEP NET represent a heterogenous group of neoplasms: carcinoids (serotoninomas and gastroenteropancreatic (insulinomas, gastrinomas, VIPomas, glucagonomas, somatostatinomas respectively, unified by their origin (neuroendocrine cells, histology and immunohistochemical profile. Unlike their frequency in adults, the rarity of these lesions in childhood makes difficult their early diagnosis. Many tumors can be asymptomatic or may show non-specific features, the diagnosis being nevertheless based on clinical signs, dosage of hormonal specific peptides, nuclear medicine imaging and pathology confirmation. Baseline tests should also include chromogranine A and sinaptophysine. Localising studies comprise CT, MRI, somatostatine receptor scintigraphy and ultrasonography completed by endoscopy. Surgery is the mainstay therapy of GEP NET, as a complete removal can potentially cure the disease; debulking and metastasis surgery, together with adjuvant medical therapy can alleviate some symptoms, sometimes for a long period. Survival is variable, depending on tumour’s type, stage, histology and also on the completeness of the treatment.

  4. Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast

    DEFF Research Database (Denmark)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-01-01

    by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained...... for the neuroendocrine markers chromogranin A and synaptophysin. Cases positive in more than 50% of the tumor cells were accepted in accordance with WHO (2003) standards of NCB. Sensitivity and specificity for TMA sections vs whole-mount sections were found to be 100% and 97.8%, respectively, suggesting that TMA......Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity added by WHO in 2003. Since then, studies have indicated that NCB potentially displays a worse prognosis than invasive ductal carcinoma. However, due to a lack of standard use of immunohistochemical staining...

  5. Ectopic pregnancy risk factors for ART patients undergoing the GnRH antagonist protocol: a retrospective study.

    Science.gov (United States)

    Weiss, A; Beck-Fruchter, R; Golan, J; Lavee, M; Geslevich, Y; Shalev, E

    2016-03-23

    In-vitro fertilization is a known risk factor for ectopic pregnancies. We sought to establish the risk factors for ectopic pregnancy in GnRH antagonist cycles examining patient and stimulation parameters with an emphasis on ovulation trigger. We conducted a retrospective, cohort study of 343 patients undergoing 380 assisted reproductive technology (ART) cycles with the GnRH antagonist protocol and achieving a clinical pregnancy from November 2010 through December 2015. Significant risk factors for ectopic pregnancy in the univariate analysis included prior Cesarean section (CS), endometriosis, mechanical factor infertility, longer stimulation, elevated estradiol and progesterone levels, GnRH agonist trigger, higher number of oocytes aspirated, and insemination technique. Independent risk factors for ectopic pregnancy in the multivariate analysis included GnRH agonist trigger, higher number of oocytes aspirated, insemination technique, and prior Cesarean section. Excessive ovarian response, IVF (as opposed to ICSI), prior Cesarean section and GnRH agonist trigger were found to be independent risk factors for ectopic pregnancy. Caution should be exercised before incorporating the GnRH agonist trigger for indications other than preventing OHSS. When excessive ovarian response leads to utilization of GnRH agonist trigger, strategies for preventing ectopic pregnancy, such as a freeze all policy or blastocyst transfer, should be considered. Further studies should elucidate whether adjusting the luteal support can reduce the ectopic pregnancy risk.

  6. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    Energy Technology Data Exchange (ETDEWEB)

    Faraco, J.; Francke, U.; Toledo, S. [Stanford Univ. School of Medicine, CA (United States)

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  7. The special relationship: glia-neuron interactions in the neuroendocrine hypothalamus.

    Science.gov (United States)

    Clasadonte, Jerome; Prevot, Vincent

    2018-01-01

    Natural fluctuations in physiological conditions require adaptive responses involving rapid and reversible structural and functional changes in the hypothalamic neuroendocrine circuits that control homeostasis. Here, we discuss the data that implicate hypothalamic glia in the control of hypothalamic neuroendocrine circuits, specifically neuron-glia interactions in the regulation of neurosecretion as well as neuronal excitability. Mechanistically, the morphological plasticity displayed by distal processes of astrocytes, pituicytes and tanycytes modifies the geometry and diffusion properties of the extracellular space. These changes alter the relationship between glial cells of the hypothalamus and adjacent neuronal elements, especially at specialized intersections such as synapses and neurohaemal junctions. The structural alterations in turn lead to functional plasticity that alters the release and spread of neurotransmitters, neuromodulators and gliotransmitters, as well as the activity of discrete glial signalling pathways that mediate feedback by peripheral signals to the hypothalamus. An understanding of the contributions of these and other non-neuronal cell types to hypothalamic neuroendocrine function is thus critical both to understand physiological processes such as puberty, the maintenance of bodily homeostasis and ageing and to develop novel therapeutic strategies for dysfunctions of these processes, such as infertility and metabolic disorders.

  8. Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation.

    Science.gov (United States)

    Burger, Laura L; Haisenleder, Daniel J; Aylor, Kevin W; Marshall, John C

    2008-11-01

    Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were collected 5 min after the last pulse, bisected, and one half processed for RNA (to measure beta subunit primary transcripts [PTs]) and the other for protein. Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3 [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9, also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240-min pulses, but phosphorylation of MAPK3 was significantly greater following slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was unchanged by pulsatile GNRH in this paradigm, but as previous results showed that GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse frequency is part of the mechanisms mediating Fhb transcriptional responses to GNRH.

  9. Regulation of Intracellular Signaling Cascades by GNRH Pulse Frequency in the Rat Pituitary: Roles for CaMK II, ERK, and JNK Activation1

    Science.gov (United States)

    Burger, Laura L.; Haisenleder, Daniel J.; Aylor, Kevin W.; Marshall, John C.

    2008-01-01

    Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were collected 5 min after the last pulse, bisected, and one half processed for RNA (to measure beta subunit primary transcripts [PTs]) and the other for protein. Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3 [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9, also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240-min pulses, but phosphorylation of MAPK3 was significantly greater following slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was unchanged by pulsatile GNRH in this paradigm, but as previous results showed that GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse frequency is part of the mechanisms mediating Fhb transcriptional responses to GNRH.. PMID:18716286

  10. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... for the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3-octreotide...

  11. Neuroendocrine tumor of the inguinal node: A very rare presentation

    Directory of Open Access Journals (Sweden)

    Niharika Bisht

    2017-12-01

    Full Text Available Neuroendocrine tumors are a broad family of tumors arising most commonly in the gastrointestinal tract and the bronchus pulmonary tree. The other common sounds are the parathyroid, pituitary and adrenal gland. Inguinal node as a primary presentation of a neuroendocrine tumor is an extremely rare presentation. We present the case of a 43-year-old-male who presented with the complaints of an inguinal node swelling without any other symptoms and on further evaluation was diagnosed to have a non-metastatic neuroendocrine tumor of the inguinal node. He was treated with a combination of chemotherapy and surgery and is presently awaiting completion chemotherapy.

  12. Neuroendocrine tumor presenting like lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Vincenzi Bruno

    2011-10-01

    Full Text Available Abstract Introduction Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. Case presentation We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. Conclusion The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor.

  13. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  14. Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours.

    Science.gov (United States)

    Rodríguez-Zarco, E; Vallejo-Benítez, A; Umbría-Jiménez, S; Pereira-Gallardo, S; Pabón-Carrasco, S; Azueta, A; González-Cámpora, R; Espinal, P S; García-Escudero, A

    2017-10-01

    Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets. Copyright © 2017 AEU. All rights reserved.

  15. Reproductive performance of dairy cows with ovarian cysts after different GnRH and cloprostenol treatments.

    Science.gov (United States)

    López-Gatius, F; López-Béjar, M

    2002-10-15

    Cystic ovarian disease is an important cause of reproductive failure and economic loss for the dairy industry. This report describes two consecutive studies. The objective of the first was to evaluate the response of cows with ovarian cysts to two therapeutic treatments. In the second study, we compared the effectiveness of the best treatment established in Study 1 with that of the Ovsynch protocol. For Study 1, cows were considered to have an ovarian cyst if it was possible to observe a single follicular structure with a follicular antrum diameter > 25 min in the absence of a corpus luteum in three ultrasonographic examinations performed at 7 days intervals. At diagnosis (Day 0), cows were assigned to one of two treatment groups. Cows in Group GnRH/CLP (n = 31) were treated with 100 microg GnRH i.m. and 500 microg cloprostenol (CLP) i.m. on Day 14. Cows in Group GnRH-CLP/CLP(n = 32) were treated with 100 microg GnRH i.m. plus 500 microg CLP i.m. on Day 0, and 500 microg CLP i.m. on Day 14. The animals were inseminated at observed estrus and monitored weekly by ultrasonography for 4 weeks or until Al. Cows in the GnRH-CLP/CLP group showed a lower cystic persistence rate (15.6% 41.9%; P 3%; P = 0.02) than those in the GnRH/CLP group. For the second study, 128 cows with ovarian cysts were randomly assigned to one of two treatment groups: cows in Group Ovsynch (n = 64) were treated with 100 microg GnRH i.m. on Day 0, 500 microg CLP on Day 7, and 100 microm GnRH i.m. 36 h later. Cows in this group were inseminated 24 h after the second GnRH dose (Ovsynch protocol). Cows in Group GnRH-CLP/CLP/GnRH (n = 64)were treated as those in the GnRH-CLP/CLP group of Study 1 but received GnRH 32 h after the second CLP treatment and were inseminated 24 h after this. A further group of cows without ovarian cysts inseminated at natural estrus served as the Group Control (n = 64). Cows in the GnRH-CLP/CLP/ GnRH group showed a lower cystic persistence rate (10.9% 17.2%; P 12.5%; P 3

  16. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

    Directory of Open Access Journals (Sweden)

    Akihiro Ohmoto

    2017-01-01

    Full Text Available Pancreatic neuroendocrine neoplasms (pNENs are rare tumors accounting for only 1%–2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC, will be needed to improve the prognosis.

  17. Gastric non-secreting neuroendocrine tumor and hypochlorhydria-related hypergastrinemia: a case report.

    Science.gov (United States)

    Biolato, Marco; Alfieri, Sergio; Ianiro, Gianluca; Pizzoferrato, Marco; Gasbarrini, Giovanni

    2013-02-22

    Zollinger-Ellison syndrome is characterized by recurrent peptic ulcers and diarrhea that result from gastrin-secreting neuroendocrine tumors of the gastrointestinal tract; nevertheless, severe hypergastrinemia may also have alternative pathogenetic explanations. A 61-year-old woman of Caucasian origin presented with a history of epigastric pain and early satiety, severe hypergastrinemia (approximately 2000 pg/mL) and a neuroendocrine polyp in the corpus of her stomach. Chronic atrophic gastritis and intestinal metaplasia was present, but she denied use of acid suppressant drugs and the results of tests for Helicobacter pylori as well as gastric parietal cell and intrinsic factor antibodies were negative. She underwent a radical gastric tangential resection. Six months later, serum gastrin was still elevated despite lack of recurrence of tumor. The clinical picture was suggestive for a hypochlorhydria-related hypergastrinemia with subsequent development of a non-secreting carcinoid. We suggest a periodic endoscopic follow-up in patients with severe hypochlorhydria-related hypergastrinemia in order to earlier detect neuroendocrine polyps.

  18. Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram

    Directory of Open Access Journals (Sweden)

    Fabiana Policeni

    2016-01-01

    Full Text Available Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient′s left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI.

  19. Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

    Science.gov (United States)

    Sargos, P; Ferretti, L; Gross-Goupil, M; Orre, M; Cornelis, F; Henriques de Figueiredo, B; Houédé, N; Merino, C; Roubaud, G; Dallaudiére, B; Richaud, P; Fléchon, A

    2014-09-01

    Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

  20. Targeted Therapies Improve Survival for Patients with Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and everolimus for patients with pancreatic neuroendocrine tumors. Updated results from the everolimus trial were published in September 2016.

  1. Neuroendocrine, immune and oxidative stress in shift workers.

    Science.gov (United States)

    Faraut, Brice; Bayon, Virginie; Léger, Damien

    2013-12-01

    Shift work is commonly associated with disturbed life rhythms, resulting in chronic exposure to circadian desynchronization and sleep restriction. Epidemiological data have shown that shift workers are at an increased risk of cardiovascular disease and breast cancer. In this review, we will explore how observed increases in neuroendocrine stress, non-specific immune responses and pro-oxidative status could act as biological mediators for these damaging health risks in shift workers. To explain these risks, compelling evidence from laboratory studies links circadian misalignment but also sleep restriction to disruptions in the neuroendocrine, immune and oxidative stress systems. Assessment of neuroendocrine, oxidative and immune stress in the shift worker population is still a limited and novel field, which may have considerable clinical relevance. Finally, we will consider the potential benefits of a countermeasure, such as napping, in minimizing the neuroendocrine and immune stress and cardiovascular risk imposed by shift work. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Energy Technology Data Exchange (ETDEWEB)

    Tonelli, Francesco, E-mail: f.tonelli@dfc.unifi.it; Giudici, Francesco [Department of Clinical Physiopathology, Surgical Unit, Medical School, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy); Giusti, Francesca; Brandi, Maria Luisa [Department of Internal Medicine, Medical School and Regional Centre for Hereditary Endocrine Tumors, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy)

    2012-05-07

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

  3. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    Department of Pathology, ESIC Medical College and PGIMSR, Rajajinagar, Bangalore, India. Abstract. Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic entity till recently due ... whole body computed tomography and magnetic resonance imaging revealed no extra mammary primary tumor.

  4. Differential Diagnosis in Neuroendocrine Neoplasms of the Larynx

    NARCIS (Netherlands)

    Hunt, Jennifer L; Ferlito, Alfio; Hellquist, Henrik; Rinaldo, Alessandra; Skálová, Alena; Slootweg, Pieter J; Willems, Stefan M; Cardesa, Antonio

    2017-01-01

    The differential diagnosis of neuroendocrine neoplasms of the larynx is broad and includes lesions of epithelial, mesenchymal, and neuroectodermal origin. These lesions have overlapping clinical and pathologic aspects and must be carefully considered in the differential diagnosis of laryngeal

  5. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  6. Anxiety, Family Functioning and Neuroendocrine Biomarkers in Obese Children

    Directory of Open Access Journals (Sweden)

    Inês Pinto

    2017-04-01

    Conclusion: These results highlight the importance of taking into account family functioning, parental mental state and gender, when investigating neuroendocrine biomarkers in obese children associated with symptoms of anxiety and depression.

  7. Evaluation of the effect of GnRH on follicular ovarian cysts in dairy cows using trans-rectal ultrasonography.

    Science.gov (United States)

    Jou, P; Buckrell, B C; Liptrap, R M; Summerlee, A J; Johnson, W H

    1999-10-01

    The objectives of this study were to evaluate ovarian changes in cows with follicular ovarian cysts following treatment with either GnRH or saline. The parameters determined were the intervals from treatment to observation of a CL and from treatment to disappearance of the cyst, and the association between serum concentrations of LH, FSH and the LH/FSH ratio, before and after treatment, with the test intervals. Thirty-nine cows were identified as having follicular cysts. The GnRH treatment induced a significant increase in LH and the LH/FSH ratio. The gonadotropin response was not associated with the intervals from treatment to CL detection or to disappearance of the cyst. Survival curves for the intervals from treatment to CL detection and cyst disappearance indicate that treatment with GnRH or saline did not yield significantly different results for either parameter. The results question the efficacy of treating cystic ovarian disease with GnRH.

  8. Evidence that GnRH decreases with gonadal steroid feedback but increases with age in postmenopausal women.

    Science.gov (United States)

    Gill, Sabrina; Sharpless, Julie L; Rado, Kimberly; Hall, Janet E

    2002-05-01

    Studies of the effects of gonadal steroid negative feedback and age on the hypothalamic-pituitary axis in postmenopausal women (PMW) have identified significant but inconsistent changes in gonadotropin dynamics. In the current study, we investigated the effect of gonadal steroid replacement and age on overall GnRH secretion estimated by using submaximal GnRH receptor blockade. Twenty-four healthy PMW, 45-55 yr (n = 13) and 70-80 yr (n = 11), were studied. Subjects were studied at baseline (BL) on no hormone replacement therapy, after 1 month of transdermal estrogen (50 microg/d; E) and again after a further month of E and 7 d of transvaginal progesterone (100 mg bid; E + P). At each admission, blood was sampled every 30 min for 4 (BL and E) or 8 h (E + P) before and 10 h after sc administration of a submaximal dose (5 microg/kg) of the NAL-GLU GnRH antagonist ([Ac-D2Nal(1), D4ClPhe(2), DPal(3), Arg(5), DGlu(AA)(6), DAla(10)] GnRH). Percent inhibition of LH was calculated by expressing the difference between the nadir following GnRH antagonist administration and the preantagonist baseline as a percent of the baseline. Physiologic E and P levels were achieved with the appropriate hormone replacement regimens. Mean LH levels decreased from baseline with E alone and decreased further with E + P (81.4 +/- 6.6, 68.2 +/- 8.1 and 48.0 +/- 4.3 IU/liter, respectively; P < 0.005). Percent inhibition of LH following submaximal GnRH receptor blockade decreased with age (57.6 +/- 1.8% in young PMW vs. 51.4 +/-2.2% in old PMW; P < 0.05) implying an increase in GnRH secretion with age. There was an increase in percent inhibition of LH in response to submaximal GnRH receptor blockade with E and a further increase with E + P (54.8 +/-1.5%, 58.8 +/- 1.9% and 69.9 +/- 2.8%, respectively; P < 0.05), indicating a progressive decrease in endogenous GnRH secretion with gonadal steroid feedback. Mean LH and FSH levels were lower at baseline in old compared with young PMW. However, the

  9. Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.

    Science.gov (United States)

    Rosati, Fabiana; Sturli, Niccolò; Cungi, Maria Chiara; Morello, Matteo; Villanelli, Fabio; Bartolucci, Gianluca; Finocchi, Claudia; Peri, Alessandro; Serio, Mario; Danza, Giovanna

    2011-04-01

    Neurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex. Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.0 nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50% after 90 min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90 min and by 3.5 times after 3 h, respectively. GnRH action is mediated by LH and 1.0 nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90 min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72 h. These data indicate for the first time that GnRH regulates both cholesterol and steroid biosynthesis in human neuronal-like cells and suggest a new physiological role for GnRH in the brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Ghrelin and pre-proghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis Grelina e pré-progrelina em tumores neuroendócrinos do estômago associados à gastrite atrófica do corpo

    Directory of Open Access Journals (Sweden)

    Letícia Figueiredo Moreira

    2010-08-01

    Full Text Available INTRODUCTION: Ghrelin is a 28 amino acid peptide secreted mainly by endocrine cells present in the gastric mucosa and acknowledged as an endogenous releaser of growth hormone. The immunohistochemical expression of ghrelin has been described in neuroendocrine tumors, and it is believed that may exert modulating action related to the growth of these tumors. OBJECTIVE: To study the presence of ghrelin and preproghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis. METHODS: Endoscopic biopsies from 15 patients with neuroendocrine tumor of the gastric mucosa associated with atrophic body gastritis were performed for immunohistochemistry, and specific chromogranin, ghrelin and preproghrelin antibodies were applied. The immunohistochemical expression was assessed in tumor cells and endocrine micronodular hyperplasia present in mucosa adjacent to the tumor, and it was classified in relation to the number of stained cells. RESULTS: Chromogranin was positive in 14 out of 15 tumors. Ghrelin and preproghrelin immunoreactive cells were detected in 11 (73% and 13 (87% tumors, respectively. There was a significant correlation between the immunohistochemical results of both antigen expressions (kappa = 81%. Ghrelin and preproghrelin expression was detected in hyperplastic nodules present in the mucosa adjacent to the tumor in seven and eight cases, respectively. There was no correlation between these results and those observed in neoplastic cells. CONCLUSION: Ghrelin and preproghrelin immunoreactive cells may be found in variable number in Type I neuroendocrine gastric tumors and in hyperplastic nodules associated with these tumors. However, it remains unclear what role these peptides play on the development of these tumors.INTRODUÇÃO: Grelina é um peptídeo de 28 aminoácidos, reconhecido como liberador endógeno do hormônio do crescimento, sendo secretado principalmente por células endócrinas da mucosa g

  11. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

    DEFF Research Database (Denmark)

    Ansel, L; Bentsen, A H; Ancel, C

    2011-01-01

    In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic...... stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity...... of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase...

  12. Enhanced incorporation of nonhydrolyzable tritium in GnRH and TRF by catalytic exchange labeling

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, J.; Bienert, M.; Niedrich, H.; Mittag, E.; Toth, G.

    1987-12-01

    Gonadotropin releasing hormone (GnRH), D-Phe/sub 6/-GnRH and thyro-tropin releasing factor (TRF) were tritiated by direct catalytic exchange using RhA1/sub 2/O/sub 3/ + HT under conditions which lead in model deuterations of N..cap alpha..-acetylhistidine amide to a high incorporation of deuterium into position 5 of the histidine ring. Specific activities up to a range of 400 GBqmmol in form of nonhydrolyzable tritium are attainable after removal of the label incorporated into position 2 of the histidine ring. A crucial reason for diminished specific activities was found to be a catalyst mediated hydrogen transfer between the peptides and traces of water, contained in the reaction mixture, competing with the tritiation.

  13. Pulmonary neuroendocrine carcinoma mimicking neurocysticercosis: a case report.

    Science.gov (United States)

    Lam, John C; Robinson, Stephen R; Schell, Andrew; Vaughan, Stephen

    2016-06-02

    Neurocysticercosis occurs when the eggs of the pork tapeworm (Taenia solium) migrate and hatch into larvae within the central nervous system. Neurocysticercosis is the most common cause of seizures in the developing world and is characterized on brain imaging by cysts in different stages of evolution. In Canada, cases of neurocysticercosis are rare and most of these patients acquire the disease outside of Canada. We report the case of a patient with multiple intracranial lesions whose history and diagnostic imaging were consistent with neurocysticercosis. Pathological investigations ultimately demonstrated that her brain lesions were secondary to malignancy. Brain metastases are considered to be the most common cause of intracranial cystic lesions. We present the case of a 60-year-old Canadian-born Caucasian woman with a subacute history of ataxia, lower extremity hyper-reflexia, and otalgia who resided near a pig farm for most of her childhood. Computed tomography and magnetic resonance imaging showed that she had multiple heterogeneous intracranial cysts, suggestive of neurocysticercosis. Despite a heavy burden of disease, serological tests for cysticercosis were negative. This result and a lack of the central scolices on neuroimaging that are pathognomonic of neurocysticercosis prompted whole-body computed tomography imaging to identify another etiology. The whole-body computed tomography revealed right hilar lymphadenopathy associated with soft tissue nodules in her chest wall and abdomen. A biopsy of an anterior chest wall nodule demonstrated high-grade poorly differentiated carcinoma with necrosis, which stained strongly positive for thyroid transcription factor-1 and synaptophysin on immunohistochemistry. A diagnosis of stage 4 metastatic small cell neuroendocrine carcinoma was made and our patient was referred for oncological palliative treatment. This case illustrates the importance of the diagnostic approach to intracranial lesions. Our patient

  14. Corifollitropin alfa in a long GnRH agonist protocol: proof of concept trial.

    Science.gov (United States)

    Fatemi, Human M; Oberyé, Janine; Popovic-Todorovic, Biljana; Witjes, Han; Mannaerts, Bernadette; Devroey, Paul

    2010-10-01

    Fifty healthy women, aged 18-39 years with no known risk of ovarian hyperstimulation were treated with 100 or 150 μg corifollitropin alfa (dependent on body weight) in a long GnRH agonist protocol. At these doses, corifollitropin alfa initiated and supported growth of a large cohort of follicles during the first week of ovarian stimulation. Copyright © 2010. Published by Elsevier Inc.

  15. GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

    DEFF Research Database (Denmark)

    Humaidan, P; Kol, Stefan; Papanikolaou, E G

    2011-01-01

    GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase...... deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering....

  16. GnRH agonist trigger versus hCG trigger in GnRH antagonist in IVF/ICSI cycles: A review article

    Directory of Open Access Journals (Sweden)

    Ashraf Alyasin

    2016-09-01

    Full Text Available Routinely, a bolus of 5.000-10.000 IU human chorionic gonadotropin (hCG is used for the final follicular maturation and ovulation as a standard method. HCG has the same effect of luteinizing hormone (LH with long half-life. It has the long lutheotrophic effect which increases the risk of ovarian hyper stimulation syndrome (OHSS. Recently, gonadotropin-releasing hormone agonist (GnRH-a trigger has been used for the induction of final follicular maturation and ovulation with the aim of reducing the OHSS risk. Several studies have shown that the releases of endogenous follicular stimulating hormone (FSH and LH after administration of GnRH agonist in in vitro fertilization (IVF cycles are able to precede the final follicular maturation leading to removal of fertile oocyte with normal development of the embryo and ultimately pregnancy. But based on the results of some studies, using GnRH-a trigger leads to defect luteal-phase resulting to reduce the implantation and clinical pregnancy rates and also increase abortion in fresh embryo transfer cycles compared to routine IVF cycle with hCG triggering . Also, in recent years, studies have continued to modify the luteal phase support, so that the fresh embryo transfer is possible too. In this review, we examined the benefits, problems, and also ways to reform GnRH agonist triggering complications.

  17. Bovine ovarian follicular cysts: in vitro effects of lecirelin, a GnRH analogue.

    Science.gov (United States)

    Rizzo, Annalisa; Cosola, Claudia; Mutinati, Maddalena; Spedicato, Massimo; Minoia, Giuseppe; Sciorsci, Raffaele Luigi

    2010-12-01

    This study investigates the mechanisms of action by which a GnRH analogue may modulate the contractility of the bovine ovarian follicular wall. The in vitro evaluation of the spontaneous basal contractility of bovine preovulatory and cystic follicles was performed, followed by testing the effects of lecirelin, a GnRH analogue, on their basal contractility. Strips of tissue in isolated organ bath were employed. In addition, to better investigate the mechanism of action of lecirelin, the study of the effects of cumulative doses of nifedipine (a calcium channel blocker), phentolamine (an α-adrenoceptor antagonist) and reserpine (an inhibitor of the vesicular up-take of catecholamines) alone and, at the highest doses employed, associated to lecirelin, was set up. The results demonstrate that in basal conditions and after the addition of lecirelin, the strips from preovulatory follicles contract significantly more than strips from cysts. Furthermore, among the patterns of contractility evoked by the three drugs employed, the one induced by nifedipine was the only one unaffected by the addition of lecirelin. The data obtained provide the hypothesis that one of the main mechanisms of action of GnRH, could involve calcium channels. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Study of Positive and Negative Consequences of Using GnRH Antagonist in Intrauterine Insemination Cycles

    Directory of Open Access Journals (Sweden)

    Maryam Bagheri

    2009-01-01

    Full Text Available Background: To assess the usefulness of premature luteinization hormone (LH surge preventionin an intrauterine insemination (IUI cycle by GnRH antagonist administration.Materials and Methods: Sixty patients with unexplained or mild male infertility or minimalto mild endometriosis were enrolled in this prospective randomized controlled trial. There weretwenty patients in group A (with GnRH antagonist and 40 patients in group B (without GnRHantagonist.In all of the participants, clomiphene citrate and human menopausal gonadotropin (CC+HMG wereused for ovarian stimulation. When at least one follicle with ≥ 16 mm diameter was seen, LH surgewas checked by a urinary LH kit. In patients with negative results, human chorionic gonadotropinwas continued in both groups, but in group A 0.25 mg Ganirelix SQ was administered for two days,,then in both groups human chorionic gonadotropin (HCG was injected on the third day and IUIwas done 36-40 hours later. Ongoing pregnancy was the primary outcome.Results: Baseline characters and clinical parameters were similar in both groups with the exceptionof ≥14 mm follicles which were higher in group A (p value= 0.003. The pregnancy rate in bothgroups was not significantly different, although it was higher in group B (10% in group A and 15%in group B.Conclusion: At least in CC+HMG stimulated cycles for IUI, the occurrence of premature LHsurge could have a useful rule and GnRH antagonist administration could be an inappropriateintervention.

  19. An unusual association of neuroendocrine tumors in MEN 1A.

    Science.gov (United States)

    Varsavsky, Mariela; Reyes-García, Rebeca; Alonso García, Guillermo; Muñoz-Torres, Manuel

    2012-09-01

    Multiple Endocrine Neoplasia type 1 is an autonomic dominant disease with a high degree of penetrance. It is characterized by combinations of over 20 different endocrine and nonendocrine tumors. A 25-year-old woman was referred for 1 year-evolution amenorrhea and bilateral galactorrhea. She also had fasting hypoglycaemia and hypercalcemia, and she was diagnosed of Multiple Endocrine Neoplasia type 1A. Resection of three parathyroid glands was performed showing hyperplasia of principal cells. Post-parathyroidectomy serum levels of calcium and intact PTH were normal but 3 years later serum calcium levels rose again. A 99mTc-sestamibi scan showed increased uptake in the low right area compatible with adenoma. After biochemical test showing probable insulinoma, somatostatin receptor scintigraphy showed a focal captation in head and body of pancreas. MRI found two nodules in the same localization. An antral gastrectomy, total pancreatoduodenectomy, colecistectomy and truncal vagotomy was performed and histopathologic examination revealed a combination of neuroendocrine tumors: gastrinomas, somastotinomas, glucagonomas and insulinomas. After surgery she started with tingling in fingers, toes and lips, and calcium levels was 5.9 mg/dl and PTH intact 3 pg/ml. A new 99m Tc-sestamibi scan showed no captation and cervical ultrasonography was normal. Now, 2 years later, she continues with normal calcium and i-PTH levels. This report represents an unusual case of MEN 1A with association of insulinomas, gastrinomas glucagonomas and somatostatinomas in the same patient.

  20. Psychological and neuroendocrine reactivity to ostracism.

    Science.gov (United States)

    Zwolinski, Jennifer

    2012-01-01

    This study used the ostracism detection theory to investigate how ostracism impacts individuals in two ways: (1) immediate poststressor needs, mood, ruminative thoughts, and desire to affiliate, and (2) short-term affective and cortisol reactivity. A total of 58 college students were randomly assigned to the inclusion or ostracism conditions of Cyberball, a virtual ball-tossing game. Immediately following the experimental manipulation, ostracized participants reported more thwarted psychological need states, more negative mood, and fewer positive ruminative thoughts, relative to their included counterparts. Ostracized participants reported a greater interest in affiliating with others in online or in-person settings. In the short-term, ostracized males reported more hostility than included males, although the scores were within expected norms for most males. There was no relation between Cyberball condition and gender across time for depression, anxiety, or positive affect. Approximately 20 min after the onset of the stressor, women in the luteal phase and women taking oral contraceptives in the ostracized group displayed higher cortisol than their counterparts in the included group. Relative to baseline, however, cortisol did not reliably increase after the onset of the stressor. Ostracized females taking oral contraceptives showed the greatest decline in cortisol, compared to included oral contraceptive users. Overall, results suggest that most of the negative effects of ostracism are immediate and limited to psychological, not neuroendocrine, responses. © 2012 Wiley Periodicals, Inc.

  1. [Neuroendocrine factors in hypertension during pregnancy].

    Science.gov (United States)

    Diaconu, Minodora; Ghiciuc, Cristina-Mihaela; Tarţău, Liliana; Lupuşoru, Cătălina-Elena

    2011-01-01

    Pregnancy induced hypertension is a condition of high blood pressure during early and mid-pregnancy. This type of hypertension is much like the chronic type, but it occurs only when the woman is pregnant and resolves completely after delivery. to evaluate some stress hormones in both normotensive and hypertensive pregnant women. The study investigated the correlation between pregnancy induced hypertension and different immune/inflammatory and other markers. This exploratory investigation was performed on pregnant women diagnosed with pregnancy-induced hypertension, admitted to the lasi Cuza Voda Hospital. The psychometric assessment was performed by using the daily stress test, daily hassle scale, blood pressure measurements, and determination of anthropometrical parameters. Some parameters, such as the neuroendocrine and immune/inflammatory ones, and specific parameters for pregnancy hypertension were determined. Our study revealed that blood pressure values presented significant differences between systolic, but not diastolic blood pressure values (p < 0.05). In 75% of subjects blood cortisol levels were not changed. Daily stress level assessment proved that low potential factors and an annoying environment had a high influence on both normotensive and hypertensive pregnant women. Hypertensive women also presented leukocytosis and thrombocytopenia. The research results showed that plasma cortisol level was higher in hypertensive pregnant women, compared with normotensives.

  2. Management of neuroendocrine tumors of unknown primary.

    Science.gov (United States)

    Alexandraki, Krystallenia; Angelousi, Anna; Boutzios, Georgios; Kyriakopoulos, Georgios; Rontogianni, Dimitra; Kaltsas, Gregory

    2017-12-04

    Neuroendocrine neoplams (NENs) are mostly relatively indolent malignancies but a significant number have metastatic disease at diagnosis mainly to the liver. Although in the majority of such cases the primary origin of the tumor can be identified, in approximately 11-22% no primary tumor is found and such cases are designated as NENs of unknown primary origin (UPO). This has significant therapeutic implications with respect to potentially resectable hepatic disease and/or application of appropriate medical therapy, either chemotherapeutic agents or targeted treatment, as the response to various treatments varies according to the origin of the primary tumor. This lack of tumor specific orientated treatment may also account for the relatively poorer prognosis of NENs of UPO compared to metastatic NENs with a known primary site. In the majority of cases the primary tumors are located in the small bowel and the lung, but a number may still elude detection. Occasionally the presence of a functional syndrome may direct to the specific tissue of origin but in the majority of cases a number of biochemical, imaging, histopathological and molecular modalities are utilized to help identify the primary origin of the tumor and direct treatment accordingly. Several diagnostic algorithms have recently been developed to help localize an occult primary tumor; however, in a number of cases no lesion is identified even after prolonged follow-up. It is expected that the delineation of the molecular signature of the different NENs may help identify such cases and provide appropriate treatment.

  3. Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)

    2016-04-15

    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

  4. Transrectal ultrasonic diagnosis of ovarian follicular cysts in goats and treatment with GnRH.

    Science.gov (United States)

    Medan, M S; Watanabe, G; Sasaki, K; Taya, K

    2004-08-01

    Cystic ovarian disease is an important cause of reproductive failure. The objective of this study was to evaluate transrectal ultrasonography as a diagnostic tool and gonadotropin-releasing hormone (GnRH) as a therapeutic approach for ovarian follicular cysts in goats. Goats were considered to have a follicular cyst(s) if a non-echoic structure >10 mm in diameter was detected in the absence of corpora lutea (CL) in three ultrasonic examinations performed at 5-day intervals. After diagnosis (Day 0), goats with ovarian follicular cysts (n = 5) were treated with a single bolus injection of 10.5 microg synthetic GnRH followed by administration of 125 microg prostaglandin F2alpha (PGF2alpha) 10 days later. Five blood samples were collected at 5-day intervals for determination of progesterone and estradiol-17beta. For detection of LH surge, blood samples were collected every 2 h. Ovulation rate was determined and pregnancy was confirmed by transrectal ultrasonography. The results showed that transrectal ultrasonography is reliable for diagnosis of ovarian follicular cysts and the mean diameter of the follicular cysts was 12.6 +/- 0.4 mm. Plasma concentrations of progesterone and estradiol-17beta at the time of diagnosis of follicular cysts (Day 0) were 0.7 +/- 0.2 ng/ml and 12.7 +/- 0.9 pg/ml, respectively. The concentration of progesterone increased to 4.0 +/- 0.5 ng/ml 10 days after administration of GnRH indicating luteinization of the ovarian follicular cysts concomitant with a decrease in the concentration of estradiol-17beta (3.5 +/- 0.4 pg/ml). Administration of GnRH to cystic goats resulted in a surge of LH within 2 h of treatment. The interval from PGF2alpha injection to the preovulatory LH surge was 62.8 +/- 1.4 h. All goats exhibited estrus 55.2 +/- 2.3 h after PGF2alpha injection and four goats out of the five ovulated. The ovulation rate was 1.5 +/- 0.3. In conclusion, results of this study suggest that transrectal ultrasonography is a reliable tool for

  5. Effect of yoga on sleep quality and neuroendocrine immune response in metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Raghavendra Mohan Rao

    2017-01-01

    Full Text Available Background: Studies have shown that distress and accompanying neuroendocrine stress responses as important predictor of survival in advanced breast cancer patients. Some psychotherapeutic intervention studies have shown have modulation of neuroendocrine-immune responses in advanced breast cancer patients. In this study, we evaluate the effects of yoga on perceived stress, sleep, diurnal cortisol, and natural killer (NK cell counts in patients with metastatic cancer. Methods: In this study, 91 patients with metastatic breast cancer who satisfied selection criteria and consented to participate were recruited and randomized to receive “integrated yoga based stress reduction program” (n = 45 or standard “education and supportive therapy sessions” (n = 46 over a 3 month period. Psychometric assessments for sleep quality were done before and after intervention. Blood draws for NK cell counts were collected before and after the intervention. Saliva samples were collected for three consecutive days before and after intervention. Data were analyzed using the analysis of covariance on postmeasures using respective baseline measure as a covariate. Results: There was a significant decrease in scales of symptom distress (P < 0.001, sleep parameters (P = 0.02, and improvement in quality of sleep (P = 0.001 and Insomnia Rating Scale sleep score (P = 0.001 following intervention. There was a decrease in morning waking cortisol in yoga group (P = 0.003 alone following intervention. There was a significant improvement in NK cell percent (P = 0.03 following intervention in yoga group compared to control group. Conclusion: The results suggest modulation of neuroendocrine responses and improvement in sleep in patients with advanced breast cancer following yoga intervention.

  6. Exogenous Kisspeptin Administration as a Probe of GnRH Neuronal Function in Patients With Idiopathic Hypogonadotropic Hypogonadism

    Science.gov (United States)

    Chan, Yee-Ming; Lippincott, Margaret F.; Butler, James P.; Sidhoum, Valerie F.; Li, Cindy X.; Plummer, Lacey

    2014-01-01

    Context: Idiopathic hypogonadotropic hypogonadism (IHH) results from defective synthesis, secretion, or action of GnRH. Kisspeptin is a potent stimulus for GnRH secretion. Objective: We probed the functional capacity of the GnRH neuronal network in patients with IHH. Participants: Eleven subjects with congenital IHH (9 men and 2 women) and one male subject who underwent reversal of IHH were studied. Six of the twelve subjects had an identified genetic cause of their IHH: KAL1 (n = 1), FGFR1 (n = 3), PROKR2 (n = 1), GNRHR (n = 1). Intervention: Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to intravenous boluses of kisspeptin (0.24 nmol/kg) and GnRH (75 ng/kg) both pre- and post-six days of treatment with exogenous GnRH (25 ng/kg sc every 2 h). Results: All subjects with abiding IHH failed to demonstrate a GnRH-induced LH response to exogenous kisspeptin. In contrast, the subject who achieved reversal of his hypogonadotropism demonstrated a robust response to kisspeptin. Conclusions: The functional capacity of the GnRH neuronal network in IHH patients is impaired, as evidenced by their inability to respond to the same dose of kisspeptin that effects a robust GnRH-induced LH response in healthy men and luteal-phase women. This impairment is observed across a range of genotypes, suggesting that it reflects a fundamental property of GnRH neuronal networks that have not been properly engaged during pubertal development. In contrast, a patient who had experienced reversal of his hypogonadotropism responded to exogenous kisspeptin. PMID:25226293

  7. Impact of Prenatal Stress on Neuroendocrine Programming

    Directory of Open Access Journals (Sweden)

    Odile Viltart

    2007-01-01

    programming strongly, notably when hormonal surges occur during sensitive periods of development, so-called developmental windows of vulnerability. Stressful events occurring during the perinatal period may impinge on various aspects of the neuroendocrine programming, subsequently amending the offspring's growth, metabolism, sexual maturation, stress responses, and immune system. Such prenatal stress-induced modifications of the phenotypic plasticity of the progeny might ultimately result in the development of long-term diseases, from metabolic syndromes to psychiatric disorders. Yet, we would like to consider the outcome of this neuroendocrine programming from an evolutionary perspective. Early stressful events during gestation might indeed shape internal parameters of the developing organisms in order to adapt the progeny to its everyday environment and thus contribute to an increased reproductive success, or fitness, of the species. Moreover, parental care, adoption, or enriched environments after birth have been shown to reverse negative long-term consequences of a disturbed gestational environment. In this view, considering the higher potential for neonatal plasticity within the brain in human beings as compared to other species, long-term consequences of prenatal stress might not be as inexorable as suggested in animal-based studies published to date.

  8. Effect of estradiol on hypothalamic GnRH and pituitary and serum LH and FSH in ovariectomized pigs.

    Science.gov (United States)

    Cox, N M; Britt, J H

    1982-10-01

    Two experiments were conducted to measure pituitary gonadotropins, hypothalamic-gonadotropin releasing hormone (GnRH) and pituitary response to GnRH during periods when serum luteinizing hormone (LH) was suppressed by estradiol-17 beta (e2) in ovariectomized pigs. In the first experiment, 10 ovariectomized gilts were assigned to two groups of five each according to time of slaughter (24 or 36 h after injection). Within each group, gilts were given corn oil (n = 2) or 400 micrograms E2 (n = 3). Neither serum nor anterior pituitary (AP) concentrations of follicle-stimulating hormone (FSH) were affected by E2. Serum LH was suppressed from 12 to 26 h after E2. Concentrations of LH in AP were unchanged at 24 h, but increased at 36 h after E2 injection. Concentrations of GnRH in medial basal hypothalamus (MBH), stalk-median eminence (SME) and hypophyseal portal area (HPA) were lower at 24 h after E2 than in oil-treated gilts. At 36 h after E2, suppressive effects of E2 on LH in serum had subsided and concentrations of LH in AP and GnRH in MBH and SME were greater than in oil-treated controls. The observation that E2 suppressed LH in serum without a detectable suppression of LH in AP led to the hypothesis that E2 had caused the suppression of serum LH by suppression of GnRH release. In a second experiment, 12 ovariectomized gilts were assigned to receive corn oil (n = 4), 400 micrograms E2 (n = 4) or 400 micrograms E2 plus GnRH (1.5 micrograms/h; n = 4). Patterns of LH in sera of E2-treated animals were similar to those in the first experiment, with serum LH in E2-treated gilts suppressed from 4 to 32 h after treatment. However, in gilts receiving GnRH in addition to E2, serum LH concentrations during 20 to 32 h after treatment were intermediate between gilts receiving E2 alone and controls. Thus the pituitary of the pig is capable of responding to GnRH when LH is normally suppressed by E2. These experiments provide two lines of evidence that suppression of serum LH by E2

  9. Bronchopulmonary Neuroendocrine Neoplasms and Their Precursor Lesions in Multiple Endocrine Neoplasia Type 1.

    Science.gov (United States)

    Bartsch, Detlef K; Albers, Max B; Lopez, Caroline L; Apitzsch, Jonas C; Walthers, Eduard M; Fink, Ludger; Fendrich, Volker; Slater, Emily P; Waldmann, Jens; Anlauf, Martin

    2016-01-01

    The prevalence and clinical behavior of bronchopulmonary neuroendocrine tumors (bNET) associated with multiple endocrine neoplasia type 1 (MEN1) are not well defined. This study aimed to determine the prevalence, potential precursor lesions and prognosis of bNET in patients with MEN1. A database of 75 prospectively collected MEN1 cases was retrospectively analyzed for bNET. Patient characteristics, imaging and treatment were evaluated. Resection specimens of operated patients were reassessed by two specialized pathologists. Available CT scans of the whole cohort were reviewed to determine the prevalence of bronchopulmonary nodules. Five of the 75 MEN1 patients (6.6%; 2 male, 3 female) developed histologically confirmed bNET after a median follow-up of 134 months. The median age at diagnosis of bNET was 47 years (range 31-67), and all patients were asymptomatic. Four patients underwent anatomic lung resections with lymphadenectomy; the remaining patient with multiple lesions had only a wedge resection of the largest bNET. Tumor sizes ranged from 7 to 32 mm in diameter, and all bNET were well differentiated. Two patients had lymph node metastases. Two of 4 reevaluated resection specimens revealed multifocal bNET, and 3 specimens showed tumorlets (up to 3) associated with multifocal areas of a neuroendocrine cell hyperplasia within the subsegmental bronchi. One bNET-related death (1.3%) occurred during long-term follow-up. Review of the available CT scans of the patients without proven bNET revealed small bronchopulmonary lesions (≥3 mm) in 16 of 53 cases (30.2%). bNET in MEN1 might be more common than previously recognized. Their natural course seems to be rather benign. Multifocal tumorlets and multifocal neuroendocrine cell hyperplasia might represent their precursor lesions. © 2015 S. Karger AG, Basel.

  10. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model

    OpenAIRE

    Azeredo, Rita; Machado, Marina; Afonso, António; Fierro-Castro, Camino; Reyes-López, Felipe E.; Tort, Lluis; Gesto, Manuel; Conde-Sieira, Marta; Míguez, Jesús M.; José L. Soengas; Kreuz, Eva; Wuertz, Sven; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamin

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 ...

  11. Neuroendocrine and immune responses undertake different fates following tryptophan or methionine dietary treatment: Tales from a teleost model

    OpenAIRE

    Azeredo, Rita; Machado, Marina; Afonso, António; Fierro-Castro, Camino; Reyes-López, Felipe E.; Tort, Lluis; Gesto, Manuel; Conde-Sieira, Marta; Míguez, Jesús M.; José L. Soengas; Kreuz, Eva; Wuertz, Sven; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamin

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 ...

  12. Neuroendocrine and immune responses undertake different fates following tryptophan or methionine dietary treatment: tales from a teleost model

    OpenAIRE

    Rita Azeredo; Marina Machado; António Afonso; Camino Fierro-Castro; Reyes-López, Felipe E.; Lluis Tort; Manuel Gesto; Marta Conde-Sieira; Míguez, Jesús M.; José L. Soengas; Eva Kreuz; Sven Wuertz; Helena Peres; Aires Oliva-Teles; Benjamin Costas

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 ...

  13. [Role of somatostatin analogs in the treatment of neuroendocrine tumours].

    Science.gov (United States)

    Cuccurullo, V; Cascini, G L; Rambaldi, P F; Mansi, L

    2001-09-01

    Current therapeutic approaches in neuroendocrine tumours include surgery, radiotherapy and polychemotherapy. Different metabolic patterns of neuroendocrine tumours allow the use of a wide range of diagnostic options in nuclear medicine, due to the presence of a wide spectrum of radiotracers electively concentrating in these neoplasms. Nuclear medicine, and in particular 111In Octreotide (OCT) scintigraphy, 123I Methaiodobenzylguanidine (MIBG) and pentavalent 99mTc-DMSA (V-DMSA), together with biohumoral markers, are currently able to locate tumours also not detectable using traditional diagnostic techniques. Somatostatin analogs, such as octreotide have become increasingly important over the years in the treatment of patients with neuroendocrine tumours. At present the therapeutic use of somatostatin analogs can be schematised as 1) pharmacological treatment (with cold octreotide); 2) surgical treatment (radioguided surgery); 3) radiometabolic treatment (with marked octreotide). The development of new synthetic molecules and new radiocompounds will probably open up interesting scenarios in the near future.

  14. HER2-Positive Neuroendocrine Breast Cancer: Case Report and Review of Literature.

    Science.gov (United States)

    Gevorgyan, Arpine; Bregni, Giacomo; Galli, Giulia; Zanardi, Elisa; de Braud, Filippo; Di Cosimo, Serena

    2016-12-01

    Neuroendocrine carcinoma is an uncommon histology for breast cancer. Our patient underwent right quadrantectomy for a neuroendocrine carcinoma in 1984 and had a bone relapse 30 years later. After thorough pathological and immunohistochemical analysis the diagnosis was confirmed and HER2 amplification was observed. Here we discuss the management, rationale and results of HER2-targeted therapy in advanced neuroendocrine breast carcinoma.

  15. Annual gonadal cycles in birds: modeling the effects of photoperiod on seasonal changes in GnRH-1 secretion.

    Science.gov (United States)

    Dawson, Alistair

    2015-04-01

    This paper reviews current knowledge of photoperiod control of GnRH-1 secretion and proposes a model in which two processes act together to regulate GnRH1 secretion. Photo-induction controls GnRH1 secretion and is directly related to prevailing photoperiod. Photo-inhibition, a longer term process, acts through GnRH1 synthesis. It progresses each day during daylight hours, but reverses during darkness. Thus, photo-inhibition gradually increases when photoperiods exceed 12h, and reverses under shorter photoperiods. GnRH1 secretion on any particular day is the net result of these two processes acting in tandem. The only difference between species is their sensitivity to photo-inhibition. This can potentially explain differences in timing and duration of breeding seasons between species, why some species become absolutely photorefractory and others relatively photorefractory, why breeding seasons end at the same time at different latitudes within species, and why experimental protocols sometimes produce results that appear counter to what happens naturally. Copyright © 2014 The Author. Published by Elsevier Inc. All rights reserved.

  16. [The neuroendocrinological and histopathological assessment of normogonadotropic azoospermic patients: the usefulness of the GnRH stimulation test].

    Science.gov (United States)

    Rosete Rossetti, R; Alvarado García, A; Bustos López, H H; Barrón Vallejo, J; Sinibaldi Gómez, J

    1994-10-01

    This study evaluates the effect of gonadotropin releasing hormone (GnRH) administration on serum levels of FSH and LH. Also, relate those results with histopathologic findings of testicular biopsies. This was a prospective, clinical trial with a control group. It was done at Department of Reproductive Biology "20 de Noviembre" Hospital, ISSSTE, México City. Fifteen azoospermic, normogonadotropic patients without testicular atrophy and ten normal men use as control group. A GnRH challenge test was made in both groups, two days after we perform a testicular biopsy in patients with azoospermia. There was no significant difference in serum LH concentrations between the two groups, neither before or after GnRH challenge test. There was a statistical difference between serum FSH values of azoospermic patients, than those of control group, the former with higher values than those of the latter. As worst testicular damage was, we found also a higher FSH value on the GnRH challenge test. The GnRH challenge test perform in azoospermic, normogonadotropic patients is very helpful to detect those patients with gonadal damage. As higher the FSH values were, we found that an abnormal testicular biopsy was also more common.

  17. Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

    Science.gov (United States)

    Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

    2016-01-01

    Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

  18. Pharmacological and toxicological assessment of a potential GnRH vaccine in young-adult male pigs.

    Science.gov (United States)

    Turkstra, J A; van der Staay, F J; Stockhofe-Zurwieden, N; Woelders, H; Meloen, R H; Schuurman, T

    2011-05-12

    Active immunization against gonadotrophin-releasing hormone (GnRH) is successfully applied to prevent boar taint in pork. In men, GnRH immunization could be an alternative to hormone therapy in patients with prostate cancer. In this study, a new GnRH vaccine formulation (a modified GnRH peptide conjugate formulated with CoVaccine adjuvant) was investigated for its pharmacological efficacy and safety in young-adult male pigs. Immunization resulted in castrate-like plasma testosterone levels in all treated pigs from week 8 until the end of the study, 30 weeks after the first immunization. Testosterone depletion retarded testes growth, reduced the relative weight of the testes and accessory sex organs, and reduced sperm counts and motility. There was no clinically relevant toxicity. Typical vaccination-related adverse reactions, such as swelling at the injection site and fever, were considered acceptable. We conclude that this GnRH vaccine efficiently and rapidly reduced serum testosterone levels, without inducing chronic toxic effects, and therefore could be applicable in both veterinary and human medicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Post-traumatic intrahepatic splenosis mimicking a neuroendocrine tumour.

    Science.gov (United States)

    Leong, Chee Weng; Menon, Tulsi; Rao, Sudhakar

    2013-03-06

    A 52-year-old man presented with abdominal pain with a background of splenectomy 25 years previously. Initial investigations lead to suspicion of a neuroendocrine tumour. Positron emission tomography octreotide scanning and chromogranin were raised. He subsequently underwent a lateral segmentectomy. The histopathology was consistent with splenosis. 1. Splenosis must be considered as differential in any patient with abdominal symptoms post-traumatic splenectomy. 2. Positron emission tomography (PET) octreotide scanning can detect splenosis giving false positives for a neuroendocrine tumour. This is the first case to describe such an association.

  20. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    Science.gov (United States)

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

  1. Metastatic breast cancer presenting as a primary hindgut neuroendocrine tumour.

    Science.gov (United States)

    Okines, Alicia F C; Hawkes, Eliza A; Rao, Sheela; VAN As, Nicholas; Marsh, Henry; Riddell, Angela; Wilson, Philip O G; Osin, Peter; Wotherspoon, Andrew C; Wetherspoon, Andrew C

    2010-07-01

    The examination of limited, potentially non-representative fragments of tumour tissue from a core biopsy can be misleading and misdirect subsequent treatment, especially in cases where a primary tumour has not been identified. This case report is of a 65-year-old woman presenting with a destructive sacral mass, diagnosed on radiological imaging and core biopsy as a hindgut neuroendocrine tumour, which on histopathological review of the subsequently resected tumour was found instead to represent a metastasis from an occult hormone-positive breast cancer with neuroendocrine features.

  2. Treatment of Ovarian Cysts in Dairy Cows with Simultaneous Administration of GnRH and PGF2α has no Clear Advantage Over the Use of GnRH Alone

    Directory of Open Access Journals (Sweden)

    Rudowska Małgorzata

    2015-04-01

    Full Text Available The aim of the study was to determine the therapeutic efficacy o f simultaneous administration of GnRH and PGF2α in dairy cows with ovarian cysts. Ovarian cyst-affected dairy cows were divided into two experimental groups: 54 cows treated with GnRH and PGF2α, and 42 cows treated with GnRH alone, whereas 22 untreated cows served as the control group. Clinical response and reproductive performance were evaluated. The cumulative disappearance was better in treated cows than in the control group; however, there were no differences between the treatment groups (92.6; 95.2% vs. 72.3%. The mean interval from calving to conception was not significantly shorter (being so by 29 d in the GnRH/PGF2α group than in the cows treated with GnRH alone (P > 0.05. The intervals from treatment to conception were also similar in these groups. The pregnancy rate in both treated groups was similar (62% and higher than in the control cows (53%. In the cows with luteal cysts, the total pregnancy rate was higher in all experimental groups; however, only in GnRH-treated cows was this difference statistically significant (77.8% vs. 50.0%, P < 0.05. With time after parturition, the pregnancy rate decreased in all groups. In general, the cows treated with GnRH and PGF2α simultaneously displayed a good clinical response and slight improvement in reproductive performance compared to the single-therapy GnRH group; however, this was not fully convincing.

  3. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial

    Science.gov (United States)

    Checa, Miguel A; Brassesco, Mario; Sastre, Margalida; Gómez, Manuel; Herrero, Julio; Marque, Laura; Brassesco, Arturo; Espinós, Juan José

    2015-01-01

    The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH) for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332) was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH) antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B) or on day 20 (protocol C) of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A). The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation). The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase) and C (stimulation on luteal phase) were compared with protocol A (standard stimulation). GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency fertility preservation in cancer patients. PMID:25709506

  4. Glucagon-like peptide-1 excites firing and increases GABAergic miniature postsynaptic currents (mPSCs in gonadotropin-releasing hormone (GnRH neurons of the male mice via activation of nitric oxide (NO and suppression of endocannabinoid signaling pathways

    Directory of Open Access Journals (Sweden)

    Imre Farkas

    2016-09-01

    Full Text Available Glucagon-like peptide-1 (GLP-1, a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9-39 (1 μM. Intracellular application of the G-protein inhibitor GDP-beta-S (2 mM impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO synthesis by L-NAME (100 μM or NPLA (1 μM or intracellular scavenging of NO by CPTIO (1 mM partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using CB1 inverse-agonist AM251 (1 μM. Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the TRPV1-antagonist AMG9810 (10 μM or the FAAH-inhibitor PF3845 (5 μM impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2-AG production. Furthermore, GLP-1 immunoreactive axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and nNOS mRNAs in GnRH-GFP neurons. Immuno-electron microscopic analysis revealed the presence of neuronal nitric oxide synthase (nNOS protein in GnRH

  5. Nasal neuroendocrine carcinoma in a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus).

    Science.gov (United States)

    Kubo, M; Matsuo, Y; Okano, T; Sakai, H; Masegi, T; Asano, M; Uchida, K; Yanai, T

    2009-01-01

    Neuroendocrine carcinoma was diagnosed in the left nasal cavity of a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus). Microscopically, the tumour consisted of sheets of anaplastic cells separated by narrow zones of fibrovascular stroma. The neoplastic cells had varying numbers of cytoplasmic granules stained by the Grimelius method. Immunohistochemically, the neoplastic cells were variably labelled for cytokeratin AE1/AE3, vimentin, chromogranin A and S-100. Ultrastructurally, some of the neoplastic cells had cytoplasmic membrane-bound dense-core granules of approximate diameter 140-240nm. The tumour had infiltrated the cerebrum and metastasized to the pituitary gland, mandibular and pulmonary lymph nodes, lungs, thyroid gland and adrenal glands.

  6. Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    Purpose. The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone (GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose......-concentration dependent absorption. Methods. The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical...

  7. Population Pharmacokinetic Modeling of a Subcutaneous Depot for GnRH Antagonist Degarelix

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    2004-01-01

    Purpose. The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone ( GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose......-concentration dependent absorption. Methods. The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical...

  8. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial

    Directory of Open Access Journals (Sweden)

    Checa MA

    2015-02-01

    Full Text Available Miguel A Checa,1,2 Mario Brassesco,2 Margalida Sastre,1 Manuel Gómez,2 Julio Herrero,3 Laura Marque,3 Arturo Brassesco,2 Juan José Espinós3 1Department of Obstetrics and Gynecology, Parc de Salut Mar, Universitat Autònoma de Barcelona, 2Centro de Infertilidad y Reproducción Humana (CIRH, 3Centro de Reproducción Asistida Sagrada Familia, Clínica Sagrada Familia, Barcelona, Spain Abstract: The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332 was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B or on day 20 (protocol C of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A. The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation. The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase and C (stimulation on luteal phase were compared with protocol A (standard stimulation. GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency

  9. Ovarian cysts in lactating dairy cows: incidence, response to GnRH, and reproductive performance

    OpenAIRE

    Santos, R.M.; Démetrio, D.G.B.; Vasconcelos, J.L.M.

    2009-01-01

    A incidência de cistos ovarianos, a resposta ao tratamento com GnRH e os efeitos da ocorrência de cisto no desempenho reprodutivo e na taxa de descarte foram determinados em vacas lactantes da raça Holandesa. Vacas lactantes (n=333) foram avaliadas semanalmente por ultrassonografia a partir da quarta semana pós-parto, visando à detecção de corpos lúteos (CL) e de folículos ovarianos maiores que 10mm. Na sétima semana pós-parto, as vacas foram classificadas: em ciclando (n=248; presença de CL ...

  10. Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Devos, Michel; Humaidan, Peter

    2013-01-01

    OBJECTIVE: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. DESIGN: Retrospective pilot study. SETTING: University-based tertiary care center. PATIENT(S): Poor ovarian responders fulfilling the Bologna criteria...... developed by European Society for Human Reproduction and Embryology Consensus Group. INTERVENTION(S): Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Endocrinologic profile and ongoing pregnancy rates. RESULT(S): Among 43 women treated...... compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). CONCLUSION(S): Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH antagonist protocol results...

  11. A preclinical pharmacokinetic/pharmacodynamic approach to determine a dose of GnRH, for treatment of ovarian follicular cyst in cattle.

    Science.gov (United States)

    Monnoyer, S; Guyonnet, J; Toutain, P L

    2004-12-01

    The objective of this study was to explore the value of a preclinical PK/PD approach to determine a gonadotropin-releasing hormone (GnRH) dose in cows using the pituitary LH response as a surrogate endpoint. Using an indirect effect model with stimulation of the LH entry rate, the in vivo basic pharmacodynamic parameters of GnRH were determined. The EC(50) of GnRH was 51 +/- 16 pg/mL, the EC(50) being the GnRH plasma concentration able to produce 50% of the maximum possible stimulation (S(max)) of the hypophysis (S(max) = 48 +/- 13). From individual PK/PD parameters, the ED(50) of GnRH, i.e. the estimated dose of GnRH required to determine half the maximum possible stimulating effect on LH release, was calculated to 62 microg/h per cow. Using the PK/PD model, the GnRH dose required to achieve a selected breakpoint value of 5 ng/mL for maximum LH concentration (surrogate value for LH concentration predicting clinical efficacy for cystic conditions), was 52 +/- 18 microg and for a standard GnRH dose of 100 microg, the mean maximum plasma LH concentration predicted by the model was 7.22 +/- 0.98 ng/mL.

  12. Neuroendocrine aspects of the response to stress.

    Science.gov (United States)

    Miller, Diane B; O'Callaghan, James P

    2002-06-01

    Disruptions in homeostasis (ie, stress) place demands on the body that are met by the activation of 2 systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Stressor-induced activation of the HPA axis and the SNS results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Here we discuss the key elements of the HPA axis and the neuroendocrine response to stress. A challenge to homeostasis (a stressor) initiates the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which in turn results in release of adrenocortiotropin hormone (ACTH) into general circulation. ACTH then acts on the adrenal cortex resulting in release of a species-specific glucocorticoid into blood. Glucocorticoids act in a negative feedback fashion to terminate the release of CRH. The body strives to maintain glucocorticoid levels within certain boundaries and interference at any level of the axis will influence the other components via feedback loops. Over- or underproduction of cortisol can result in the devastating diseases of Cushing's and Addison's, respectively, but less severe dysregulation of the HPA axis can still have adverse health consequences. These include the deposition of visceral fat as well as cardiovascular disease (eg, atherosclerosis). Thus, chronic stress with its physical and psychological ramifications remains a persistent clinical problem for which new pharmacological treatment strategies are aggressively sought. To date, treatments have been based on the existing knowledge concerning the brain areas and neurobiological substrates that subserve the stress response. Thus, the CRH blocker, antalarmin, is being investigated as a treatment for chronic stress because it prevents CRH from having its

  13. Serum Anti-Müllerian Hormone Levels in Precocious Puberty Girls according to Stage of GnRH Agonist Treatment.

    Science.gov (United States)

    Nam, Hyo Kyoung; Kim, Hye Ryun; Rhie, Young Jun; Lee, Kee Hyoung

    2017-03-01

    Few studies have investigated the long-term effects of gonadotropin-releasing hormone (GnRH) agonist treatment on the reproductive function of central precocious puberty (CPP) girls. In this cross-sectional study, we assessed the ovarian function by analyzing the serum anti-Müllerian hormone (AMH) levels of CPP girls. Our study included 505 CPP girls subdivided into 5 groups according to the GnRH agonist treatment stage: group A (before treatment, n = 98), group B (3 months after initiation, n = 103), group C (12 months after initiation, n = 101), group D (24 months after initiation, n = 101), and group E (6 months after discontinuation, n = 102). We compared the serum AMH levels of the CPP girls with those of 100 bone age-matched controls (before treatment: n = 55; after discontinuation: n = 45). At baseline, the mean AMH level of the CPP girls was 5.9 ± 3.6 ng/mL. The mean AMH level after 3 months of the GnRH agonist treatment was lower (4.7 ± 3.2 ng/mL, P = 0.047) than that at baseline and recovered after 12 months of treatment. Six months after discontinuation, the AMH levels were similar to those at pre-treatment. Before and after the GnRH agonist treatment, the AMH levels were similar to those of the bone age-matched controls. In the precocious puberty girls, the AMH levels based on the GnRH agonist treatment stage were all within the normal reference range. The results of this study suggest that GnRH agonist treatment has no adverse effects on the reproductive function.

  14. Neuroendocrine tumors of the lung: major radiologic findings in a series of 22 histopathologically confirmed cases

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcel Koenigkam, E-mail: marcelk46@yahoo.com.br [Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP-USP), SP (Brazil); Department of Diagnostic and Interventional Radiology, Heidelberg University (Germany); Barreto, Andre Rodrigues Facanha [Clinica Radius, Clinica Sao Carlos Imagem and Santa Casa de Misericordia de Fortaleza, Fortaleza, CE (Brazil); Chagas Neto, Francisco Abaete [Program of Health Sciences Applied to the Locomotor System - Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, SP (Brazil); Muglia, Valdair Francisco; Elias Junior, Jorge [Division of Radiology, Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRPUSP), Ribeirao Preto, SP (Brazil)

    2012-07-15

    Objective: To describe key imaging findings in a series of cases of primary neuroendocrine tumors of the lung (NTLs), with emphasis on computed tomography changes. Materials And Methods: Imaging studies of 22 patients (12 men, mean age 60 years) with histopathologically confirmed diagnosis, evaluated in the author's institution during the last five years were retrospectively reviewed by two radiologists, with findings being consensually described focusing on changes observed at computed tomography. Results: The authors have described five typical carcinoids, three atypical carcinoids, three large-cell neuroendocrine carcinomas (LCNCs), and 11 small-cell lung cancers (SCLCs). Only one typical carcinoid presented the characteristic appearance of central endobronchial nodule with distal pulmonary atelectasis, while the others were pulmonary nodules or masses. The atypical carcinoids corresponded to peripheral heterogeneous masses. One out of the three LCNCs was a peripheral homogeneous mass, while the others were ill-defined and heterogeneous. The 11 SCLCs corresponded to central, infiltrating and heterogeneous masses with secondary pleuropulmonary changes. Calcifications were absent both in LGNCs and SCLCs. Metastases were found initially and also at follow-up of all the cases of LCNCs and SCLCs. Conclusion: Although some imaging features may be similar, radiologic findings considered together with clinical information may play a relevant role in the differentiation of histological types of NTLs. (author)

  15. Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Jacob Ø; von Holstein, Sarah L; Prause, Jan U

    2014-01-01

    hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.......A 71-year-old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological...... and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary...

  16. Everolimus Effect on Gastrin and Glucagon in Pancreatic Neuroendocrine Tumors

    NARCIS (Netherlands)

    Pavel, Marianne E.; Chen, David; He, Wei; Cushman, Stephanie; Voi, Maurizio; de Vries, Elisabeth G. E.; Baudin, Eric; Yao, James C.

    Objectives: The pharmacodynamic effects of everolimus on gastrointestinal hormone levels have not been described in patients with pancreatic neuroendocrine tumors (pNETs). We report the effects of everolimus on gastrin and glucagon levels in patients with progressive pNETin RADIANT-1 (a single-arm

  17. Surgical Treatment of an Isolated Metastatic Myocardial Neuroendocrine Tumor.

    Science.gov (United States)

    Caldeira, Christiano C B; Sayad, Dany; Strosberg, Jonathan; Faber, Cristiano; Saouma, Samer; Michaud, Tabitha

    2016-02-01

    We describe a patient diagnosed with a neuroendocrine tumor of the small intestine metastatic to the heart who underwent successful cardiac metastasectomy. The tumor was located on the right ventricle free wall, obstructing the right ventricular outflow tract. There was no valvular involvement. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

    NARCIS (Netherlands)

    Halmos, Gyorgy B; van der Laan, Tom P; van Hemel, Bettien M; Dikkers, Frederik G; Slagter-Menkema, Lorian; van der Laan, Bernard F A M; Schuuring, Ed

    The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were

  19. Neuroendocrine Tumour in a Patient with Neurofibromatosis Type 1 ...

    African Journals Online (AJOL)

    We report the case of an HIV-positive female patient with neurofibromatosis type 1 who was treated for recurrent peptic ulcer disease and later developed diabetes mellitus and chronic diarrhoea. A metastasising somatostatinoma was histologically proven and evidence of a concomitant gastrin-producing neuroendocrine ...

  20. Backbone metal cyclization: Novel {sup 99m}Tc labeled GnRH analog as potential SPECT molecular imaging agent in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barda, Yaniv; Cohen, Nasi; Lev, Vered; Ben-Aroya, Nurit; Koch, Yitzhak; Mishani, Eyal; Fridkin, Mati; Gilon, Chaim E-mail: gilon@vms.huji.ac.il

    2004-10-01

    Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted to the pituitary where it binds to specific receptors on the gonadotropes to regulate gonadotropic hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) synthesis and secretion. Specific GnRH receptors are overexpressed in breast, prostatic, ovarian, and other tumors. The aim of this study was to synthesize a cyclic GnRH analog with high affinity to GnRH receptors that can be radiolabeled with {sup 99m}Tc. A precyclic GnRH analog, [Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (Gn-2), containing two hemi-chelator groups was synthesized. It was cyclized applying the recently reported backbone metal cyclization (BMC) approach, to obtain cyclo(Re(O)1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (cyclo[Re(O)-Gn-2]). For comparative evaluations, Gn-2 was oxidized on-resin to yield cyclo(S-S,1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH, (cyclo[S-S-Gn-2]). The binding affinity of cyclo[Re(O)-Gn-2] to rat pituitary membranes showed IC{sub 50} of 50nM, compared to IC{sub 50} = 10 nM in the native GnRH. Cyclo({sup 99m}Tc(O)1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (cyclo[{sup 99m}Tc(O)-Gn-2]) was synthesized from Gn-2 and showed similar chromatographic behavior to its rhenium surrogate.

  1. Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of fasting.

    Science.gov (United States)

    Tuziak, Sarah M; Volkoff, Hélène

    2013-12-01

    Melanin-concentrating hormone (MCH) is classically known for its role in regulating teleost fish skin color change for environmental adaptation. Recent evidence suggests that MCH also has appetite-stimulating properties. The gonadotropin-releasing hormone (GnRH) peptide family has dual roles in endocrine control of reproduction and energy status in fish. Atlantic cod (Gadus morhua) are a commercially important aquaculture species inhabiting the shores of Atlantic Canada. In this study, we examine MCH and GnRH transcript expression profiles during early development as well as in central and peripheral tissues and quantify juvenile Atlantic cod MCH and GnRH hypothalamic mRNA expressions following food deprivation. MCH and GnRH3 cDNAs are maternally deposited into cod eggs, while MCH has variable expression throughout early development. GnRH2 and GnRH3 mRNAs "turn-on" during mid-segmentation once the brain is fully developed. For both MCH and GnRH, highest expression appears during the exogenous feeding stages, perhaps supporting their functions as appetite regulators during early development. MCH and GnRH transcripts are found in brain regions related to appetite regulation (telencephalon/preoptic area, optic tectum/thalamus, hypothalamus), as well as the pituitary gland and the stomach, suggesting a peripheral function in food intake regulation. Atlantic cod MCH mRNA is upregulated during fasting, while GnRH2 and GnRH3 transcripts do not appear to be influenced by food deprivation. In conclusion, MCH might be involved in stimulating food intake in juvenile Atlantic cod, while GnRHs may play a more significant role in appetite regulation during early development. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Kim, Ji Hoon; Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2015-05-01

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  3. Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zoghi, Masoumeh; Niazi, Ali [Islamic Azad Univ., Arak (Iran, Islamic Republic of). Dept. of Chemistry; Jalilian, Amir R.; Johari-daha, Fariba; Alirezapour, Behrouz [Nuclear Science and Technology Research Institute (NSTRI) (Iran, Islamic Republic of). Radiation Application Research School; Ramezanpour, Sorour [K.N. Toosi Univ. of Technology, Tehran (Iran, Islamic Republic of). Peptide Chemistry Research Center

    2016-08-01

    Optimized total synthesis, radiolabeling and quality control of [{sup 68}Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared using generator-based [{sup 68}Ga]GaCl{sub 3} and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5-7 min at 95 C followed by separation using C{sub 18} cartridge (radiochemical purity ∼99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.

  4. The correlation between GnRH stimulation testing and obstetric ultrasonographic parameters in precocious puberty.

    Science.gov (United States)

    Binay, Cigdem; Simsek, Enver; Bal, Cengiz

    2014-11-01

    The aim of this study was to determine reliable cut-off levels of basal gonadotropin and to assess the correlation of obstetric ultrasound parameters with the GnRH stimulation test. The GnRH stimulation test was performed in a cohort of young female patients who presented at our hospital for the evaluation of early signs of puberty. Using receiver operating curves (ROCs), the sensitivity and specificity of basal luteinising hormone (LH), follicle stimulating hormone (FSH), basal and stimulated LH/FSH ratio, oestradiol levels and ultrasonographic parameters were evaluated at each level, and the area under curve (AUC) was measured. One hundred female children were assessed. We found that LH levels, peak LH/FSH ratio, fundal/cervical ratio, uterus length, and ovarian volume were reliable predictors of central precocious puberty (CPP). Cut-off levels of basal LH and the peak LH/FSH ratio had high specificity in our cohort. In addition, obstetric ultrasound parameters represent reliable predictors for the diagnosis of CPP.

  5. The control of reproduction in finfish species through GnRH treatments

    Directory of Open Access Journals (Sweden)

    Simona Rainis

    2010-01-01

    Full Text Available Fish in captivity can show some dysfunctions, at different levels, in the physiological processes of reproduction, due to  the lack of synthesis or release of gonadotropins (GtHs by hypophysis. As a consequence, a worsening of quality and  quantity of spawned gametes, or a lack of egg and sperm spawning, can be observed. The farmers can act on fish repro-  ductive cycle manipulating the environmental parameters of rearing, the diet, the genetics or using GnRH treatments.  Nowadays, they are used mainly GnRH, synthesized in laboratory as analogues. These releasing factors, naturally pro-  duced by hypothalamus, let to overcome the technological and biological limits of the “traditional” hormonal treatments  with hCG, being more effective, cheaper and easily available on market. This article makes a historical survey of the con-  ditioning treatments for fish reproduction and also considers the future perspectives of these treatments, examining the  topics that research will have to focus, in order to make these treatments common worldwide, in any hatchery and for  each farmed  species of finfish. 

  6. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

    Science.gov (United States)

    Kos-Kudła, Beata; Blicharz-Dorniak, Jolanta; Strzelczyk, Janusz; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Falconi, Massimo; Foltyn, Wanda; Handkiewicz-Junak, Daria; Hubalewska-Dydejczyk, Alicja; Jarząb, Barbara; Junik, Roman; Kajdaniuk, Dariusz; Kamiński, Grzegorz; Kolasińska-Ćwikła, Agnieszka; Kowalska, Aldona; Król, Robert; Królicki, Leszek; Krzakowski, Maciej; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Lipiński, Michał; Londzin-Olesik, Magdalena; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nawrocki, Sergiusz; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; Starzyńska, Teresa; Steinhof-Radwańska, Katarzyna; Sworczak, Krzysztof; Syrenicz, Anhelli; Szawłowski, Andrzej; Szczepkowski, Marek; Wachuła, Ewa; Zajęcki, Wojciech; Zemczak, Anna; Zgliczyński, Wojciech; Zieniewicz, Krzysztof

    2017-01-01

    Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

  7. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization

    NARCIS (Netherlands)

    B.C.J.M. Fauser (Bart); D. de Jong (Danielle); F. Olivennes; H. Wramsby; C. Tay; J. Itskovitz-Eldor; H.G. van Hooren

    2002-01-01

    textabstractIn a randomized multicenter study, the efficacies of two different GnRH agonists were compared with that of hCG for triggering final stages of oocyte maturation after ovarian hyperstimulation for in vitro fertilization. Ovarian stimulation was conducted by recombinant

  8. Duodenal neuroendocrine tumor and the onset of severe diabetes mellitus in a US veteran

    Directory of Open Access Journals (Sweden)

    Lauren Murray

    2016-01-01

    Full Text Available Objective: Neuroendocrine tumors are neoplasms derived from endocrine cells, most commonly occurring in the gastrointestinal tract. Duodenal neuroendocrine tumors are rare tumors averaging 1.2–1.5 cm, and most are asymptomatic. Common presentation is abdominal pain, upper gastrointestinal bleed, constipation, anemia, and jaundice. Methods: An adult, Black, male patient with newly diagnosed diabetes mellitus presented to the emergency department with elevated liver function test and fatigue. Results: Magnetic resonance cholangiopancreatography demonstrated a large obstructing mass (3.6 cm × 4.4 cm × 3 cm within the second and third portions of the duodenum at the ampulla. Esophagogastroduodenoscopy demonstrated an ulcerated duodenal mass that was biopsied. Immunohistochemical stains were positive for synaptophysin, chromogranin B, and CK7. Chromogranin A was in normal range. Post-Whipple procedure demonstrated a 5.5 cm × 4.1 cm × 2.9 cm duodenal mass with invasion of the subserosal tissue of the small intestine, a mitotic rate of 2 per high-power field, and antigen Ki-67 of 2%–5%. Conclusion: This case raises the question as to if the patient developed diabetes mellitus due to the tumor size and location or if the new onset of diabetes was coincidental. This case also demonstrates the importance of a proficient history and physical.

  9. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report

    Directory of Open Access Journals (Sweden)

    Nicolas M. Orsi

    2016-08-01

    Full Text Available Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10–12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade, arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area.

  10. Genomic alterations in neuroendocrine cancers of the ovary.

    Science.gov (United States)

    Yaghmour, George; Prouet, Philippe; Wiedower, Eric; Jamy, Omer Hassan; Feldman, Rebecca; Chandler, Jason C; Pandey, Manjari; Martin, Mike G

    2016-08-26

    As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes. Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12-75] and 26 years [range 8-40], respectively) than patients with NET-O 62 [range 13-76] or SCLC 66 [range 36-86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified. No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.

  11. Heterogeneity for IGF-II production maintained by public goods dynamics in neuroendocrine pancreatic cancer.

    Science.gov (United States)

    Archetti, Marco; Ferraro, Daniela A; Christofori, Gerhard

    2015-02-10

    The extensive intratumor heterogeneity revealed by sequencing cancer genomes is an essential determinant of tumor progression, diagnosis, and treatment. What maintains heterogeneity remains an open question because competition within a tumor leads to a strong selection for the fittest subclone. Cancer cells also cooperate by sharing molecules with paracrine effects, such as growth factors, and heterogeneity can be maintained if subclones depend on each other for survival. Without strict interdependence between subclones, however, nonproducer cells can free-ride on the growth factors produced by neighboring producer cells, a collective action problem known in game theory as the "tragedy of the commons," which has been observed in microbial cell populations. Here, we report that similar dynamics occur in cancer cell populations. Neuroendocrine pancreatic cancer (insulinoma) cells that do not produce insulin-like growth factor II (IGF-II) grow slowly in pure cultures but have a proliferation advantage in mixed cultures, where they can use the IGF-II provided by producer cells. We show that, as predicted by evolutionary game theory, producer cells do not go extinct because IGF-II acts as a nonlinear public good, creating negative frequency-dependent selection that leads to a stable coexistence of the two cell types. Intratumor cell heterogeneity can therefore be maintained even without strict interdependence between cell subclones. Reducing the amount of growth factors available within a tumor may lead to a reduction in growth followed by a new equilibrium, which may explain relapse in therapies that target growth factors.

  12. Hysteroscopic myomectomy outcomes after 3-month treatment with either Ulipristal Acetate or GnRH analogues: a retrospective comparative study.

    Science.gov (United States)

    Sancho, Javier Monleón; Delgado, Verónica Serrano de la Cruz; Valero, Maria José Nuñez; Soteras, Marta Gurrea; Amate, Vicente Payá; Carrascosa, Antonio Abad

    2016-03-01

    Ulipristal Acetate (UPA) modifies the endometrium, as well as fibroids, and therefore it might make hysteroscopic surgery more difficult. To confirm that pre-treatment with UPA is as safe and effective an option as pre-treatment with GnRH analogues, considered the gold standard. We present the first series of 26 hysteroscopic myomectomies after 3 months treatment with UPA and we compare the results with a series of 24 cases pretreated with GnRH analogues. This was a retrospective cohort study between July 2013 and May 2015. We analyszed patients with submucous myomas >2.5 in diameter. Hysteroscopic myomectomy was performed after 3 months of treatment with either UPA (5mg daily) or the GnRH agonist (3.75mg/month). Both groups were similar in age, myoma initial size and classification. There were no significant differences between UPA and GnRHa treated groups in terms of percentage of myomas resected (93% vs 98%), duration of surgery (38 vs 37min), fluid deficit (200 vs 350ml) and complications. In the surgeon's subjective opinion, UPA treatment was associated with an easier resection. Based on our experience, previous treatment with UPA does not difficult Hhysteroscopic myomectomy. Endometrial changes have no impact on surgery. Safety and feasibility are comparable to hysteroscopic myomectomies with previous treatment with GnRH analogues. This allows us to take advantage of the reduction in size of fibroids before surgery with less side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Active immunization against GnRH in ovine (Ovis aries: testicular morphometry, histopathology and endocrine responses in prepubertal ram lambs

    Directory of Open Access Journals (Sweden)

    Gutierrez-Reinoso MA

    2017-08-01

    Full Text Available The main objective of the present research was to assess the effects of an active immunization against GnRH on male reproductive function as an alternative to surgical sterilization evaluating testicular morphometry, histopathological alterations and plasma gonadotropin levels in prepubertal ram lambs. Dorper ram lambs (age= 2 months; control group, n= 5; treatment group, n=15 were immunised by using an anti-GnRH vaccine (two administrations spaced 15d developed by linking a GnRH homologous molecule to tetanus toxoid (clostridial toxoid with aluminum hydroxide as coadjuvant. To determine the effectiveness of the vaccination protocol, testicular morphometry was evaluated (length, width, mean volume and total volume together with histopathological alterations in testicular tissue samples (seminiferous tubule diameters, spermatogonia per testis and sperm presence and endocrine responses (ELISA from blood samples (FSH, LH, testosterone and cortisol plasma levels. Morphometric parameters (testicular length, width and volume were significantly reduced in vaccinated animals with respect to the control group (p0.05. In conclusion, prepubertal active immunization against GnRH led to marked differences on testes morphometry and activity in ovine species, however, it did not affect endocrine levels nor spermatogenesis in all individuals studied showing a partial vaccination effect in some of them. Thus, taking into account the heterogeneous dysfunctional responses obtained, different vaccination assays and strategies should be tested before active immunization against GnRH is considered as a viable alternative to conventional surgical sterilization.

  14. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

    NARCIS (Netherlands)

    Oostdijk, W; Rikken, B; Schreuder, S; Otten, Barto; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S

    1996-01-01

    Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were

  15. FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat

    NARCIS (Netherlands)

    Schuiling, GA; Valkhof, N; Koiter, TR

    The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin(R); 10 IU/injection) lowered the spontaneous pre-ovulatory

  16. Use of GnRH to induce an accessory corpus luteum in buffaloes fixed time artificially inseminated

    Directory of Open Access Journals (Sweden)

    P.S. Baruselli

    2010-02-01

    Full Text Available The objective of this study was to induce an accessory corpus luteum (CL in buffaloes fixed time artificially inseminated. Two hundred and forty buffaloes received the treatment sequence GnRH/PGF2α/GnRH after which were inseminated artificially. Six days after the insemination, the animals were divided in two groups (G1 = Control and G2 = GnRH and received 0 μg or 25 μg of GnRH to induce an accessory CL. After twenty four days (D40, pregnancy diagnosis was performed by ultrasonography and 79 buffalo (G1, n = 39; G2, n = 40 were randomly selected to verify the ovary status by ultrasound. Fifty three pregnant buffaloes (G1, n = 32; G2, n = 21 were followed to verify the birth rate. Data were analyzed by Chi-square test. The conception rate, the accessory CL rate and the birth rate were higher in G2 than in G1 (P<0.05. The use of GnRH to induce an accessory CL in buffaloes increased the conception and birth rates. Thus, the increase of the cost of Ovsynch protocol with the thirty dose of GnRH is rewarded by the increment on conception and birth rates and reduction of days open.

  17. Neuroendocrine stimulatory tests of hypothalamus-pituitary-adrenal axis in psoriasis and correlative implications with psychopathological and immune parameters.

    Science.gov (United States)

    Karanikas, Evangelos; Harsoulis, Faidon; Giouzepas, Ioannis; Griveas, Ioannis; Chrisomallis, Fotios

    2009-01-01

    Psoriasis constitutes one of the most representative examples of psychosomatic disorders. The published work investigating the psychological parameters and the way they interact during the course of the disease is extensive, whereas only a few studies have focused on the neuroendocrine framework of psoriasis. In the present study, the objective was to investigate the neuroendocrine parameters of psoriasis and the way they interact with psychopathological and immune variables. Patients with psoriasis (n=24) and the same number of matched healthy controls underwent psychiatric evaluation with interviews and psychometric questionnaires. Both of the groups underwent the corticotropin-releasing hormone (CRH) test and the dexamethasone suppression test (DST) to investigate functional parameters of the hypothalamus-pituitary-adrenal (HPA) axis. The evaluation of immune variables included the estimation of the distribution of T-cell and natural killer lymphocytes. Levels of depressive and anxiety features were increased within subjects with psoriasis and they were significantly correlated with stressful life events and the extent of the disease. The adrenocorticotrophic hormone and cortisol levels increased after CRH infusion without significant differences between the two groups and the psoriatic subjects' cortisol suppression after DST was within normal range, though relatively blunted. No significant correlations were identified among neuroendocrine, psychopathological and immune parameters. No particular neuroendocrine profile has been identified among psoriatic patients and the hypothesized interaction with psychopathological and immune parameters was not replicated. Nevertheless, it is still premature to exclude the possibility that a subtle latent alteration of the HPA axis function might exist, in psoriasis, either stemming from the psychopathology or from the disease per se.

  18. Active immunization with recombinant GnRH fusion protein in boars reduces both testicular development and mRNA expression levels of GnRH receptor in pituitary.

    Science.gov (United States)

    Fang, Fugui; Li, Haidong; Liu, Ya; Zhang, Yunhai; Tao, Yong; Li, Yunsheng; Cao, Hongguo; Wang, Suolu; Wang, Lin; Zhang, Xiaorong

    2010-06-01

    Immunization using recombinant maltose binding protein-gonadotropin releasing hormone (MBP-GnRH6) altered both testicular development and transcription of the pituitary GnRH receptor (GnRHR) gene in boars. Scrotal measurement and blood samples were taken at 4-week interval after immunization at 9 weeks of age. The concentrations of testosterone and anti-GnRH antibodies in serum were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The results showed that active immunization with MBP-GnRH6 increased the serum concentration of anti-GnRH antibodies (Pimmunized animals as compared with MBP immunized boars. MBP-GnRH6 immunized pigs exhibited mounting behavior 4 weeks later than MBP immunized boars. No mature spermatozoa were observed from MBP-GnRH6 immunized animals. By real-time quantitative PCR analysis, the amount of GnRHR mRNA in the pituitary tissue was found to be significantly lower in MBP-GnRH6 immunized animals than in controls (P<0.05). These data demonstrate that recombinant MBP-GnRH6 was effective in immunological castration in boars. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  19. Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

    Science.gov (United States)

    Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

    2015-07-01

    We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

  20. Effect of GnRH and hCG on progesterone concentration and ovarian and luteal blood flow in diestrous mares.

    Science.gov (United States)

    Brito, L F C; Baldrighi, J M; Wolf, C A; Ginther, O J

    2017-01-01

    The objective of the present study was to investigate the effect of reproductive hormones (GnRH, hCG, LH and progesterone) on the regulation of corpus luteum (CL) and ovarian blood flow. Diestrous mares received a single treatment of saline, 100μg gonadorelin (GnRH), or 1500IU hCG 10days after ovulation. Plasma LH and progesterone concentrations, resistance index (RI) for ovarian artery blood-flow, and percentage of corpus luteum (CL) with color-Doppler signals of blood flow were determined immediately before treatment (hour 0) and at hours 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 6. In the GnRH group, LH increased (PhCG groups. Progesterone concentration was not different among groups. In the GnRH group, RI tended (PhCG group, two transient RI decreases (PhCG group. The similarity among groups in progesterone concentration indicated that changes in progesterone were not involved in the GnRH and hCG stimulation of ovarian vascular perfusion. Effects of treatment might have been mediated through LH; however, since hCG biological activity is primarily LH-like, the differences in timing and degree of ovarian and luteal blood flow changes after GnRH or hCG administration in the present study suggest that GnRH might have a direct effect on ovarian blood vessels and vascular control. Copyright © 2016. Published by Elsevier B.V.

  1. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study.

    Science.gov (United States)

    Muñoz, Manuel; Cruz, María; Humaidan, Peter; Garrido, Nicolás; Pérez-Cano, Inmaculada; Meseguer, Marcos

    2013-06-01

    To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist + hCG triggering versus GnRH antagonist + GnRH agonist triggering) affect embryo development and kinetics. In a retrospective cohort study in the Instituto Valenciano de Infertilidad (IVI) Alicante and the Instituto Universitario-IVI Valencia, Spain, 2817 embryos deriving from 400 couples undergoing oocyte donation were analysed. After controlled ovarian stimulation and IVF/intracytoplamic sperm injection, the timing of embryonic cleavages was assessed by a video time-lapse system. The results were analysed using Student's t test for comparison of timings (hours) and Chi-squared test for comparison of proportions. A p-value < 0.05 was considered to be statistically significant. Embryos from cycles co-treated with GnRH antagonist + GnRH agonist (n = 2101) cleaved faster than embryos deriving from patients co-treated with GnRH agonist + hCG (n = 716): these differences were significant at the first stages of development but they disappeared as long as the embryo developed. Assessing embryo quality in terms of morphokinetic characteristics, we did not find significant differences between the two groups. By adopting a time-lapse video system, we can suggest that the type of protocol used for controlled ovarian stimulation influences embryo kinetics of development but these variations are not reflected in embryo quality. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Treatment Options for Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  3. Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

    Science.gov (United States)

    Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

    2010-12-01

    Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

  4. Dynamics of GnRH Neuron Ionotropic GABA and Glutamate Synaptic Receptors Are Unchanged during Estrogen Positive and Negative Feedback in Female Mice.

    Science.gov (United States)

    Liu, Xinhuai; Porteous, Robert; Herbison, Allan E

    2017-01-01

    Inputs from GABAergic and glutamatergic neurons are suspected to play an important role in regulating the activity of the gonadotropin-releasing hormone (GnRH) neurons. The GnRH neurons exhibit marked plasticity to control the ovarian cycle with circulating estradiol concentrations having profound "feedback" effects on their activity. This includes "negative feedback" responsible for suppressing GnRH neuron activity and "positive feedback" that occurs at mid-cycle to activate the GnRH neurons to generate the preovulatory luteinizing hormone surge. In the present study, we employed brain slice electrophysiology to question whether synaptic ionotropic GABA and glutamate receptor signaling at the GnRH neuron changed at times of negative and positive feedback. We used a well characterized estradiol (E)-treated ovariectomized (OVX) mouse model to replicate negative and positive feedback. Miniature and spontaneous postsynaptic currents (mPSCs and sPSCs) attributable to GABA A and glutamatergic receptor signaling were recorded from GnRH neurons obtained from intact diestrous, OVX, OVX + E (negative feedback), and OVX + E+E (positive feedback) female mice. Approximately 90% of GnRH neurons exhibited spontaneous GABA A -mPSCs in all groups but no significant differences in the frequency or kinetics of mPSCs were found at the times of negative or positive feedback. Approximately 50% of GnRH neurons exhibited spontaneous glutamate mPSCs but again no differences were detected. The same was true for spontaneous PSCs in all cases. These observations indicate that the kinetics of ionotropic GABA and glutamate receptor synaptic transmission to GnRH neurons remain stable across the different estrogen feedback states.

  5. Epidural vs intramuscular administration of lecirelin, a GnRH analogue, for the resolution of follicular cysts in dairy cows.

    Science.gov (United States)

    Rizzo, Annalisa; Annalisa, Rizzo; Campanile, Debora; Debora, Campanile; Mutinati, Maddalena; Maddalena, Mutinati; Minoia, Giuseppe; Giuseppe, Minoia; Spedicato, Massimo; Massimo, Spedicato; Sciorsci, Raffaele Luigi; Luigi, Sciorsci Raffaele

    2011-06-01

    Bovine follicular cysts are an ovarian disorder of dairy cows associated with abnormal estrous behaviour and infertility. The treatment of choice is intramuscular administration of a GnRH analogue, which acts by triggering pituitary release of LH. However, the presence of GnRH and GnRH receptors on spinal cord and ovary in some species, and the kind of innervation of the ovary, let us hypothesize that GnRH and its analogues may also act when administered by epidural route, as happens for other drugs. Therefore the aim of this study was to compare the effects of epidural vs intramuscular administration of lecirelin (a GnRH analogue) on FC regression, estrus detection and pregnancy outcomes. The study was conducted on 220 Friesian cows affected by follicular cysts, divided among 4 groups: Group L(epid) and Group L(im) received, respectively 50 μg of lecirelin in the epidural space and intramuscular; Group C(epid) and Group C(im) were used as control groups. In Group L(epid), estrus induction and pregnancy rates were significantly higher than in Group L(im). The results of this study show that the epidural administration of lecirelin promoted the remission of follicular cysts and an improvement of reproductive parameters compared to intramuscular administration. Thus, an alternative therapeutical approach is available for FC treatment, in order to obtain an easier restoration of the ovarian activity, especially in those cases refractory to classical therapeutic approaches. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Phosphorylation substrates for protein kinase C in intact pituitary cells: characterization of a receptor-mediated event using novel gonadotropin-releasing hormone analogues

    Energy Technology Data Exchange (ETDEWEB)

    Strulovici, B.; Tahilramani, R.; Nestor, J.J. Jr.

    1987-09-22

    The involvement of protein kinase C in the signal transduction of gonadotropin-releasing hormone (GnRH) action was investigated with a GnRH superagonist, partial agonists, and antagonists in intact rat pituitary cells. Exposure of /sup 32/P-labeled cells to GnRH or to the superagonist (D-Nal(2)/sup 6/)GnRH induced the enhanced phosphorylation of 42-, 34-, 11-, and 10-kDa proteins and the dephosphorylation of a 15-kDa protein as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography. This effect was blocked in a dose-dependent manner by potent GnRG antagonists. Downregulation of protein kinase C by prolonged incubation of the pituitary cells with high concentrations of active phorbol esters abolished protein kinase C activity and also prevented the phosphorylation induced by GnRN, or (D-Nal(2)/sup 6/)GnRH. The same effect was obtained by preincubating the cells with the protein kinase C inhibitor H-7. In this study the authors identify for the first time physiological substrates for protein kinase C in intact pituitary cells. They demonstrate a close quantitative correlation between the extent of translocation of protein kinase C, levels of phosphorylation of specific substrates in the intact cells, and the biological activity of the GnRH analogues with varying affinity for the GnRH receptor. These data strengthen the contention that the physiological effects of GnRH are primarily mediated via the phosphatidylinositol/Ca/sup 2 +/ signal transfer system and represent a first step toward defining the physiological substrates of protein kinase C and their role in the cascade of events that starts upon binding of GnRH to its receptor.

  7. EFECTO DE LA GnRH EN EL PROCESO DEL RECONOCIMIENTO MATERNAL DE LA PREÑEZ SOBRE LA SUPERVIVENCIA EMBRIONARIA EN ALPACAS

    OpenAIRE

    Araínga R., Mariluz; Práctica privada; Leyva V., Víctor; Laboratorio de Reproducción y Obstetricia Veterinaria, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.; García V., Wilber; Estación Experimental del Centro de Investigación IVITA-Maranganí, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.; Franco Ll., Enrique; Estación Experimental del Centro de Investigación IVITA-Maranganí, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.

    2013-01-01

    The effect of GnRH administered around the time of maternal recognition of prenancy on the embryonic survival rate was studied. It was used 67 adult female alpacas sexually receptive to the male, and bearing a preovulatory follicle ≥7mm, detected by rectal ultrasonography. Animals were distributed in three groups: G0 (n=23) as control; G1 (n=22) received 6 µg GnRH on day 4 after ovulation; and G2 (n=22) received 4 µg GnRH on days 8 and 9 after ovulation. The ocurrence of ovulation was confirm...

  8. Efficiency of fixed-time artificial insemination using a progesterone device combined with GnRH or estradiol benzoate in Nellore heifers

    Directory of Open Access Journals (Sweden)

    Vinícius Antônio Pelissari Poncio

    2015-10-01

    Full Text Available he use of estrogens in artificial insemination protocols for cattle is the least expensive and most efficient method currently available. However, the trend to prohibit the use of estrogens for this purpose has made it necessary to find alternatives that replace estrogens without compromising the reproductive performance of the animals. The objective of this study was to evaluate conception rates in Bos indicus beef heifers treated with a progesterone device (P4 combined with GnRH or an estradiol ester. On day 0, pubertal Nellore heifers (n = 100 received an intravaginal device containing 1 g P4 and were randomly divided into two groups. The GnRH group (n = 49 received an intramuscular injection of 100 µg GnRH, while the E2 group (n = 51 received 2 mg estradiol benzoate (EB. The P4 device was removed after 5 (GnRH group or 8 days (E2 group, followed by an injection of 125 µg of the PGF2α, analog cloprostenol. On that occasion, the E2 group received an additional injection of 300 IU eCG. Twenty-four hours later, the GnRH group received a second injection of 125 µg cloprostenol, while the E2 group received 1 mg EB. The heifers were inseminated 72 (GnRH group or 54 hours (E2 group after removal of the P4 device. At the time of insemination, the GnRH group received additionally an injection of 100 µg GnRH. Estrus was monitored during the period of cloprostenol injection until the time of artificial insemination and pregnancy was diagnosed 40 days after insemination by transrectal ultrasonography. The data were analyzed by Fisher’s exact test. The pregnancy rate was 38.8% and 31.4% in the GnRH and E2 groups, respectively (P>0.05. The ovarian condition of the heifers (estrus or anestrus tended to influence (P=0.07 pregnancy rates in the GnRH group, but not in the E2 group. At the time of artificial insemination, 33.3% of heifers in the GnRH group showed signs of estrus versus 88.2% in the E2 group (P<0.05. However, the time of estrus

  9. [Surgical treatment of gastroentero-pancreatic neuroendocrine tumor].

    Science.gov (United States)

    Ohtsuka, Takao; Takahata, Shunichi; Ueda, Junji; Ueki, Takashi; Nagai, Eishi; Mizumoto, Kazuhiro; Shimizu, Shuji; Tanaka, Masao

    2013-07-01

    The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is resection. Because it is difficult to determine the histological grade of NET before operation, the treatment strategy is usually made based on an imaging study including the tumor's size. Some selected gastrointestinal NETs are indicated for endoscopic resection, while others are resected surgically with lymph node dissection. The types of resections for pancreatic NETs vary from enucleation to pancreatectomy with or without regional lymph node dissection, based on the type of excessive hormone, tumor size, distance from the main pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic metastases are also resected, if indicated, and even in patients having unresectable metastatic lesions, multidisciplinary therapy including reduction surgery of over 90% of tumor volume might lead to a favorable prognosis. Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while there is no evidence to support adjuvant therapy for curatively resected well-differentiated NET.

  10. Insulinoma and gastrinoma syndromes from a single intrapancreatic neuroendocrine tumor.

    Science.gov (United States)

    Lodish, Maya B; Powell, Anathea C; Abu-Asab, Mones; Cochran, Craig; Lenz, Petra; Libutti, Steven K; Pingpank, James F; Tsokos, Maria; Gorden, Phillip

    2008-04-01

    The insulinoma syndrome is marked by fasting hypoglycemia and inappropriate elevations of insulin. The gastrinoma syndrome is characterized by hypergastrinemia, ulcer disease, and/or diarrhea. Rarely, insulinoma and gastrinoma coexist in the same patient simultaneously. Our objective was to determine the cause of a patient's hypoglycemic episodes and peptic ulcer disease. This is a clinical case report from the Clinical Research Center of the National Institutes of Health. One patient with hypoglycemic episodes and peptic ulcer disease had a surgical resection of neuroendocrine tumor. The patient was found to have a single tumor cosecreting both insulin and gastrin. Resection of this single tumor was curative. A single pancreatic neuroendocrine tumor may lead to the expression of both the hyperinsulinemic and hypergastrinemic syndromes.

  11. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Josef Zihl

    2015-05-01

    Full Text Available Endocrine dysfunction is a common effect of traumatic brain injury (TBI. In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

  12. Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment.

  13. Massive gastrointestinal bleed due to multiple gastric neuroendocrine tumors

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    Vishal Sharma

    2015-01-01

    Full Text Available Gastric neuroendocrine tumors (G-NETs are uncommon lesions which are usually diagnosed on histological evaluation of gastric polyps. These may occur sporadically or due to hypergastrinemia in the setting of atrophic gastritis or Zollinger-Ellison Syndrome. Large lesions may ulcerate and result in gastrointestinal bleeding. However, massive gastrointestinal bleeding is rare in patients with NETs. We report a 60-year-old lady who presented with massive gastrointestinal bleeding due to multiple G-NETs.

  14. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

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    Ahmed M Ragab Shalaby

    2016-01-01

    Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

  15. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

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    Arpad eDobolyi

    2012-10-01

    Full Text Available The G-protein coupled parathyroid hormone 2 receptor (PTH2R is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand,tuberoinfundibular peptide of 39 residues (TIP39, is synthesized in only 2 brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control

  16. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress

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    Sarah J Spencer

    2013-06-01

    Full Text Available Feeding behavior is closely regulated by neuroendocrine mechanisms that can be influenced by stressful life events. However, the feeding response to stress varies among individuals with some increasing and others decreasing food intake after stress. In addition to the impact of acute lifestyle and genetic backgrounds, the early life environment can have a life-long influence on neuroendocrine mechanisms connecting stress to feeding behavior and may partially explain these opposing feeding responses to stress. In this review I will discuss the perinatal programming of adult hypothalamic stress and feeding circuitry. Specifically I will address how early life (prenatal and postnatal nutrition, early life stress, and the early life hormonal profile can program the hypothalamic-pituitary-adrenal (HPA axis, the endocrine arm of the body’s response to stress long-term and how these changes can, in turn, influence the hypothalamic circuitry responsible for regulating feeding behavior. Thus, over- or under-feeding and / or stressful events during critical windows of early development can alter glucocorticoid (GC regulation of the HPA axis, leading to changes in the GC influence on energy storage and changes in GC negative feedback on HPA axis-derived satiety signals such as corticotropin-releasing-hormone. Furthermore, peripheral hormones controlling satiety, such as leptin and insulin are altered by early life events, and can be influenced, in early life and adulthood, by stress. Importantly, these neuroendocrine signals act as trophic factors during development to stimulate connectivity throughout the hypothalamus. The interplay between these neuroendocrine signals, the perinatal environment, and activation of the stress circuitry in adulthood thus strongly influences feeding behavior and may explain why individuals have unique feeding responses to similar stressors.

  17. A comparative therapeutic management of anoestrus in buffaloes using insulin and GnRH

    Directory of Open Access Journals (Sweden)

    R. D. Purkayastha

    2015-06-01

    Full Text Available Aim: Anoestrus is one of the most common functional disorders of the reproductive cycle in buffaloes. In spite of technical advancement, there is no single cure for the management of anoestrus. Therefore, the aim of this study was to find out the efficacy of gonadotropic releasing hormone (GnRH and metabolic hormone for the management of true anoestrus in buffaloes. Materials and Methods: The experimental animals were selected on the basis of history, gyneco-clinical examinations and progesterone estimation. Deworming was done with Fenbendazole and thereafter mineral mixture was given @ 50 g per animal per day for 10 days in all the selected buffaloes before the start of treatment. The selected buffaloes were randomly divided into four groups (n=25. In Group I, buffaloes were administered 20 μg of buserelin intramuscularly. Buffaloes of Group II were administered long-acting insulin @ 0.25 IU/Kg body weight subcutaneously for 5 consecutive days. In Group III, buffaloes were treated with a combination of insulin and buserelin in the above-mentioned doses whereas buffaloes of Group IV were kept as untreated control. Results: The higher oestrus induction (64% vs. 28% was found in Group III and differed significantly (p<0.05 as compared to control group. The conception rate (69.23% vs. 66.66% was also found higher in Group III but did not differ significantly among the treated groups. The mean time taken for the onset of oestrus was recorded significantly shorter in insulin (8.80±0.69 and GnRH (7.60±0.92 days alone and as compared to other (Group III, 14.43±0.83 and Group IV, 20.57±1.69 days groups. Conclusion: The results of this study indicated better fertility response using Insulin plus Buserelin in true anoestrus buffaloes under field conditions.

  18. EFFECT OF GnRH AND PHOSPHORUS IN DELAYED PUBERTAL SURTI BUFFALO HEIFERS

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    H.B. Dhamsaniya

    2016-06-01

    Full Text Available The study was conducted on eighteen delayed pubertal Surti buffalo heifers, divided into three equal groups (6 in each to evaluate the efficacy of GnRH alone and in combination of phosphorus. The buffalo heifers in Group-I and Group-II were treated with Buserelin acetate (5 ml, IM. Buffalo heifers in Group-II also received additional injection of Toldimphos sodium (10 ml, IM at 3 day interval for 4 times, while buffalo heifers in Group-III served as control. The percentage of induced estrus was highest (83.33% in each treated groups as compared to control group (50%. The mean estrus induction intervals were significantly (P<0.05 shorter in Group-I (20.20 ± 2.18 days and Group-II (18.80 ± 2.32 days as compared to control group (30.24 ± 0.81 days. The conception rate at induced estrus was highest in Group-II (50% followed by Group-I (33.33%. The plasma progesterone levels being significantly lowest on the day of estrus (less than 0.5 ng/ml as compared to pre-treatment days in all groups. The mean total protein and triglycerides levels were differed significantly between the groups on the day of estrus and being significantly higher in Group-II as compared to Group-I and III on that day. A significantly higher level of cholesterol in both treatment groups as compared to the control group during different intervals and also being higher on the day of estrus as compared to pre-treatment days. The mean plasma glucose levels were differed nonsignificantly between and within the treatment and control groups. It is concluded that estrus can be successfully induced in delayed pubertal heifers with the use of GnRH alone and in combination with phosphorus.

  19. Neuroendocrine brake for the treatment of morbid obesity. Preliminary report

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    Aureo Ludovico de Paula

    2005-06-01

    Full Text Available Objectives: To demonstrate the preliminary results of a newtechnique named neuroendocrine brake, for surgical treatment ofmorbid obesity. Methods: In November 2003, three patientsunderwent the neuroendocrine brake operation performed by thelaparoscopic approach. The mean age was 46.4 years; all patientswere female. Mean BMI was 42.3 kg/m2. The patients selectedpresented some relative or absolute contraindications to the useof gastrointestinal bypass techniques, including gastric ulcer anda family history of gastric malignancy(1 and chronic anemia (2.All patients had associated diseases, including type II diabetesmellitus (2, hypertension (2, obstructive sleep apnea (1,dyslipidemia (3, cholecystolithiasis (1, gastric ulcer (1 andchronic anemia (2. The laparoscopic technique consisted of anileal interposition at the proximal jejunum and longitudinalgastrectomy. Results: There was no conversion to open surgery orpostoperative complications. Sixteen months later, the meanpercentage of initial body weight loss was 44.6% and the meanBMI was 24.3 kg/m2. Glucose, triglyceride and cholesterol levelswere normalized, and sleep apnea showed remission. Conclusion:In spite of the reduced number of patients and short term followup, the good results suggest that the neuroendocrine brake maybecome an option for surgical treatment of morbid obesity in thenear future.

  20. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

  1. Add-back therapy with GnRH analogues for uterine fibroids.

    Science.gov (United States)

    Moroni, Rafael M; Martins, Wellington P; Ferriani, Rui A; Vieira, Carolina S; Nastri, Carolina O; Candido Dos Reis, Francisco José; Brito, Luiz Gustavo

    2015-03-20

    Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects. To assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms. We searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014. Randomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion. Two authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the

  2. Temozolomide as second or third line treatment of patients with neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Sørensen, Jens B; Federspiel, Birgitte

    2012-01-01

    Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results....

  3. The GPR54-Kisspeptin complex in reproductive biology: neuroendocrine significance and implications for ovulation induction and contraception.

    Science.gov (United States)

    Sills, Eric Scott; Walsh, Anthony P H

    2008-12-01

    KISS1 encodes the kisspeptin (KP) family of peptides which were originally characterised as potent antimetastatic agents in breast cancer and malignant melanoma cells. One member of this family of arginine-phenylalanine amide peptides, KP-54, was subsequently identified as the natural ligand for the G-protein coupled receptor-54 (GPR54). In addition to its importance as a metastatic suppressor, KP has been found to play a major neuroregulatory role in governing endogenous gonadotropin release by its modulation of the hypothalamic-pituitary-gonadal (HPG) axis. In humans, KISS1 mRNA has been localised to the hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Although GPR54 is expressed in human pituitary cells, it is not presently known if gonadotrope cells themselves are targets for significant KP activity. It was recently shown that full disruption of the KP/GPR54 complex resulted in hypogonadotropic hypogonadism. Indeed, evidence now suggests that KP/GPR54 signalling during gestation is necessary for sexual differentiation and implicates activation of the KP/GPR54 complex as the single most important upstream event regulating GnRH release. Several compelling studies have placed KP as the leading candidate molecule responsible for initiating puberty, making this receptor-ligand complex of fundamental importance to the neuroendocrinology of reproduction. Here, we discuss key KP/GPR54 discovery events and present an evolution of KP biology in the context of recent animal and human experimental work. With evidence pointing to proper KP/GPR54 signalling as the principal trigger for activation of GnRH neurons and subsequent ovulation, elucidation of how this pathway is modulated is likely to bring novel pharmacologic strategies for fertility treatment (and contraception) within reach. Because the physiological significance KP is now acknowledged to extend well beyond cancer biology (and may also contribute to the pathophysiology of pre

  4. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    Science.gov (United States)

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-10-13

    Poorly-differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly-differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports and pathology slides were reviewed for demographics, clinical history and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1 and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61years old with 18 males and 19 females. The colorectum (n=20) was the most common primary site, other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%), and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly-differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017. Published by Elsevier Inc.

  5. Effect of antidepressants on neuroendocrine axis in humans.

    Science.gov (United States)

    Meltzer, H Y; Fang, V S; Tricou, B J; Robertson, A

    1982-01-01

    Unlike neuroleptic drugs, the effect of antidepressant drugs on the neuroendocrine axis in man is highly variable and may or may not be intimately related to their antidepressant action. However, the limited neuroendocrine data available does shed some light on the mechanism of action of these agents and raises some important questions, particularly about the regulation of PRL secretion and the interaction between various neurotransmitter systems. At one end of the spectrum, the ability of nomifensine and buproprion to lower serum PRL levels, presumably due to their ability to block the reuptake of DA by tuberoinfundibular DA neurons, suggests that it may be necessary to reconsider the conclusion that these neurons lack a DA reuptake mechanism or that these two agents are antidepressant by virtue of their ability to block DA uptake. Similarly, the inability of amphetamine or methylphenidate to decrease serum PRL levels in man suggests important differences between the tuberoinfundibular DA neurons in man and the rat. These findings also call into question the ability of these agents to block DA uptake or increase DA release in the tuberoinfundibular DA neurons. The finding that fluoxetine raises serum PRL levels, even in one subject, whereas zimelidine has not yet been shown to do so, and that fluoxetine does not potentiate the ability of 5-HTP to stimulate PRL secretion, has raised important questions about the role of 5-HT in PRL and GH regulation in man and the relationship between 5-HT and DA neurons in man. The occasional increase in serum PRL levels found in patients treated with lithium or the MAO inhibitor phenelzine are suggestive of important interindividual differences which may be revealed by neuroendocrine studies, differences which could be valuable in understanding the mechanism of action of these agents - e.g., does lithium decrease DA receptor sensitivity? - and fundamental aspects of neuroendocrine regulation - e.g., do the MAO inhibitors

  6. Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learning.

    Science.gov (United States)

    Drozdov, Ignat; Kidd, Mark; Nadler, Boaz; Camp, Robert L; Mane, Shrikant M; Hauso, Oyvind; Gustafsson, Bjorn I; Modlin, Irvin M

    2009-04-15

    A more accurate taxonomy of small intestinal (SI) neuroendocrine tumors (NETs) is necessary to accurately predict tumor behavior and prognosis and to define therapeutic strategy. In this study, the authors identified a panel of such markers that have been implicated in tumorigenicity, metastasis, and hormone production and hypothesized that transcript levels of the genes melanoma antigen family D2 (MAGE-D2), metastasis-associated 1 (MTA1), nucleosome assembly protein 1-like (NAP1L1), Ki-67 (a marker of proliferation), survivin, frizzled homolog 7 (FZD7), the Kiss1 metastasis suppressor (Kiss1), neuropilin 2 (NRP2), and chromogranin A (CgA) could be used to define primary SI NETs and to predict the development of metastases. Seventy-three clinically and World Health Organization pathologically classified NET samples (primary tumor, n = 44 samples; liver metastases, n = 29 samples) and 30 normal human enterochromaffin (EC) cell preparations were analyzed using real-time polymerase chain reaction. Transcript levels were normalized to 3 NET housekeeping genes (asparagine-linked glycosylation 9 or ALG9, transcription factor CP2 or TFCP2, and zinc finger protein 410 or ZNF410) using geNorm analysis. A predictive gene-based model was constructed using supervised learning algorithms from the transcript expression levels. Primary SI NETs could be differentiated from normal human EC cell preparations with 100% specificity and 92% sensitivity. Well differentiated NETs (WDNETs), well differentiated neuroendocrine carcinomas, and poorly differentiated NETs (PDNETs) were classified with a specificity of 78%, 78%, and 71%, respectively; whereas poorly differentiated neuroendocrine carcinomas were misclassified as either WDNETs or PDNETs. Metastases were predicted in all cases with 100% sensitivity and specificity. The current results indicated that gene expression profiling and supervised machine learning can be used to classify SI NET subtypes and accurately predict metastasis

  7. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  8. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Rehfeld, Anders Aagaard; Plass, Mireya; Døssing, Kristina

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site...... and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire...... and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions...

  9. Serum levels of antimüllerian hormone in early maturing girls before, during, and after suppression with GnRH agonist

    DEFF Research Database (Denmark)

    Hagen, Casper P; Sørensen, Kaspar; Anderson, Richard A

    2012-01-01

    To evaluate whether serum antimüllerian hormone (AMH) levels are affected in early maturing girls, and whether pituitary suppression by long-acting GnRH agonist (GnRH-a) affects AMH.......To evaluate whether serum antimüllerian hormone (AMH) levels are affected in early maturing girls, and whether pituitary suppression by long-acting GnRH agonist (GnRH-a) affects AMH....

  10. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support

    DEFF Research Database (Denmark)

    Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P

    2013-01-01

    Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?......Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?...

  11. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  12. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

    Science.gov (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

    2011-12-01

    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

  13. A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients.

    Science.gov (United States)

    Davar, Robab; Rahsepar, Mozhgan; Rahmani, Elham

    2013-01-01

    This study aims to verify if luteal estradiol pre-treatment improves IVF/ICSI outcomes in a GnRH antagonist protocol as compared with a micro dose GnRH agonist protocol in poor-responding patients. A total of 116 IVF/ICSI cycles were included in this prospective randomized single blind clinical trial. The selected women were randomly assigned to receive an estradiol pre-treatment in a GnRH antagonist protocol (daily oral Estradiol Valerate 4 mg preceding the IVF cycle from the 21st day until the first day of the next cycle) or in oral contraceptive pill micro dose GnRH agonist protocol. The patients in the luteal estradiol protocol required more days of stimulation (10.9 ± 1.6 vs. 10.2 ± 1.8) and a greater gonadotropin requirement (3,247.8 ± 634.6 vs. 2,994.8 ± 611 IU), yet similar numbers of oocytes were retrieved and fertilized. There was no significant difference between the two groups in terms of the implantation rates (9.8 vs. 7.9 %) and the clinical pregnancy rates per transfer (16.3 vs. 15.6 %). This study demonstrates that the use of estradiol during a preceding luteal phase in a GnRH antagonist protocol can provide similar IVF outcomes when compared to a micro dose GnRH agonist protocol.

  14. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

    Directory of Open Access Journals (Sweden)

    Lund Eiliv

    2009-07-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

  15. Global gene expression in neuroendocrine tumors from patients with the MEN1 syndrome

    Directory of Open Access Journals (Sweden)

    Laramie Jason M

    2005-02-01

    Full Text Available Abstract Background Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100 is an autosomal dominant disorder characterized by endocrine tumors of the parathyroids, pancreatic islets and pituitary. The disease is caused by the functional loss of the tumor suppressor protein menin, coded by the MEN1 gene. The protein sequence has no significant homology to known consensus motifs. In vitro studies have shown menin binding to JunD, Pem, Smad3, NF-kappaB, nm23H1, and RPA2 proteins. However, none of these binding studies have led to a convincing theory of how loss-of-menin leads to neoplasia. Results Global gene expression studies on eight neuroendocrine tumors from MEN1 patients and 4 normal islet controls was performed utilizing Affymetrix U95Av2 chips. Overall hierarchical clustering placed all tumors in one group separate from the group of normal islets. Within the group of tumors, those of the same type were mostly clustered together. The clustering analysis also revealed 19 apoptosis-related genes that were under-expressed in the group of tumors. There were 193 genes that were increased/decreased by at least 2-fold in the tumors relative to the normal islets and that had a t-test significance value of p Conclusion This is the first analysis of global gene expression in MEN1-associated neuroendocrine tumors. Many genes were identified which were differentially expressed in neuroendocrine tumors arising in patients with the MEN1 syndrome, as compared with normal human islet cells. The expression of a group of apoptosis-related genes was significantly suppressed, suggesting that these genes may play crucial roles in tumorigenesis in this syndrome. We identified a number of genes which are attractive candidates for further investigation into the mechanisms by which menin loss causes tumors in pancreatic islets. Of particular interest are: FGF9 which may stimulate the growth of prostate cancer, brain cancer and endometrium; and IER3 (IEX-1, PHLDA2

  16. The Function of Neuroendocrine Cells in Prostate Cancer

    Science.gov (United States)

    2015-06-20

    University of Rochester Medical Center School of Medicine and Dentistry , Rochester, NY. Corresponding Authors: Jiaoti Huang, UCLA David Geffen School of...and transcribed as part of the miR-106b25 poly- cistron. It is overexpressed in several human cancers, including pediatric brain tumors (28...Handler MH, Vibhakar R, Foreman NK. Survey of MicroRNA expression in pediatric brain tumors. Pediatr Blood Cancer 2011;56:211–6. 29. Petrocca F, Visone R

  17. The Function of Neuroendocrine Cells in Prostate Cancer

    Science.gov (United States)

    2012-04-01

    weighs and measures the prostate, inks its surface with Indian ink (to assess the status of surgical margins on histologic sections) and slices the...for pathologic diagnosis. Slices 2 and 4 are divided into 4 quadrants and additional ink of different colors is used for orientation indicating right vs...medium (DMEM), sodium pyru- vate, L-glutamine, penicillin, and streptomycin were purchased from Hyclone; charcoal /dextran-treated FBS medium was

  18. General Information about Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)

    Science.gov (United States)

    ... History Committees of Interest Legislative Resources Recent Public Laws Careers Visitor Information Search Search Home Cancer Types Pancreatic Cancer Patient Pancreatic Cancer Patient Pancreatic ...

  19. Kisspeptin/Gpr54-independent GnRH activity in Kiss1 and Gpr54 mutant mice

    OpenAIRE

    Chan, Yee-Ming; Broder-Fingert, Sarabeth; Wong, Kai Mee; Seminara, Stephanie B.

    2009-01-01

    The kisspeptin/Gpr54 signaling pathway plays a critical role in reproduction by stimulating the secretion of GnRH, yet mice carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial sexual maturation. For instance, a proportion of female Kiss1−/− and Gpr54−/− mice exhibit vaginal oestrus, and some male Kiss1−/− and Gpr54−/− mice exhibit spermatogenesis.

  20. GnRH antagonist and letrozole co-treatment in diminished ovarian reserve patients: a proof-of-concept study.

    Science.gov (United States)

    Olgan, Safak; Humaidan, Peter

    2017-03-01

    The current study aimed to investigate the effects of luteal gonadotropin-releasing hormone (GnRH) antagonist pretreatment on the outcomes of diminished ovarian reserve (DOR) patients who were treated using a FSH/letrozole/GnRH antagonist (FLA) protocol. Thus, patients who had luteal GnRH antagonist pretreatment (AFLA) prior to stimulation were compared to patients who had the FLA protocol, only. An electronic database was used to identify patients and stimulation characteristics. Women who had a total antral follicle count (AFC) of protocol were compared to 76 cycles using a FLA protocol, only. The total gonadotropin dose, duration of stimulation, and peak estradiol levels were comparable between the groups (p>0.05). However, the AFLA group had significantly more metaphase-2 (MII) oocytes (p=0.009), a higher oocyte maturity rate (MII/total oocytes) (p=0.029), and a higher mature oocyte yield (MII/AFC) (p=0.020) with more cleaved embryos (p=0.036), and a significantly reduced number of canceled cycles (26.7% vs. 44.7%; p=0.048). The clinical pregnancy rate per cycle was 22.2% vs. 13.2% (p=0.195) in the AFLA and FLA groups, respectively. Interestingly, a subgroup analysis including ESHRE Bologna criteria poor responder patients showed that the luteal administration of GnRH antagonist resulted in better outcomes when compared with the FLA protocol alone. In conclusion, luteal GnRH antagonist pretreatment improves ovarian stimulation parameters and reproductive outcomes in poor ovarian reserve IVF patients. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  1. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

    DEFF Research Database (Denmark)

    Janson, Eva Tiensuu; Sorbye, Halfdan; Welin, Staffan

    2014-01-01

    BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine...

  2. Neuroendocrine dysregulations in sexually abused children and adolescents: a systematic review

    NARCIS (Netherlands)

    Bicanic, I. A. E.; Meijer, M.; Sinnema, G.; van de Putte, E. M.; Olff, M.

    2008-01-01

    Several studies provided evidence for neuroendocrine dysregulations in adults with a history of child sexual abuse. This review focuses on neuroendocrine studies in sexually abused children and adolescents, dating from January 1, 1990 to January 1, 2007 and obtained from a systematic Medline Indexed

  3. Neuroendocrine reactivity and recovery from work with different physical and mental demands

    NARCIS (Netherlands)

    Sluiter, JK; Frings-Dresen, MHW; van der Beek, AJ; Meijman, TF; Heisterkamp, SH

    Objectives The purpose of this study was to examine the extent to which the type or nature (physical, mental or mixed mental and physical) of work and work characteristics is related to the course of neuroendocrine reactivity and recovery from work. Methods Neuroendocrine reactivity and recovery

  4. Behavior of feral horses in response to culling and GnRH immunocontraception

    Science.gov (United States)

    Ransom, Jason I.; Powers, Jenny G.; Garbe, Heidi M.; Oehler, Michael W.; Nett, Terry M.; Baker, Dan L.

    2014-01-01

    Wildlife management actions can alter fundamental behaviors of individuals and groups,which may directly impact their life history parameters in unforeseen ways. This is especially true for highly social animals because changes in one individual’s behavior can cascade throughout its social network. When resources to support populations of social animals are limited and populations become locally overabundant, managers are faced with the daunting challenge of decreasing population size without disrupting core behavioral processes. Increasingly, managers are turning to fertility control technologies to supplement culling in efforts to suppress population growth, but little is quantitatively known about how either of these management tools affects behavior. Gonadotropin releasing hormone (GnRH) is a small neuropeptide that performs an obligatory role in mammalian reproduction and has been formulated into the immunocontraceptive GonaCon-BTM. We investigated the influences of this vaccine on behavior of feral horses (Equus caballus) at Theodore Roosevelt National Park, North Dakota, USA, for a year preceding and a year following nonlethal culling and GnRH-vaccine treatment. We observed horses during the breeding season and found only minimal differences in time budget behaviors of free-ranging female feral horses treated with GnRH and those treated with saline. The differences observed were consistent with the metabolic demands of pregnancy and lactation. We observed similar social behaviors between treatment groups, reflecting limited reproductive behavior among control females due to high rates of pregnancy and suppressed reproductive behavior among treated females due to GnRH-inhibited ovarian activity. In the treatment year, band stallion age was the only supported factor influencing herding behavior (P stallions decreased 50.7% following treatment and culling (P reproductive, and agonistic behavior in the year following culling and treatment (P < 0.04). These

  5. Neuroendocrine Tumors of the Lung: Current Challenges and Advances in the Diagnosis and Management of Well-Differentiated Disease.

    Science.gov (United States)

    Hendifar, Andrew E; Marchevsky, Alberto M; Tuli, Richard

    2017-03-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, most commonly originating from the lungs and gastrointestinal tract. Lung NETs can be classified as well differentiated (low-grade typical carcinoids [TCs] and intermediate-grade atypical carcinoids [ACs]) and poorly differentiated (high-grade large cell neuroendocrine carcinoma or SCLC). The incidence of these tumors is increasing, but disease awareness remains low among thoracic specialists, who are often involved in the diagnosis and early treatment for these patients. An accurate and timely diagnosis can ensure the implementation of appropriate treatment and have a substantial impact on prognosis. However, lung NET classification and diagnosis, particularly for TCs/ACs, are complicated by several factors, including a variable natural history and nonspecific symptoms. Surgery remains the only curative option for TCs/ACs, but there is a lack of consensus between lung NET management guidelines regarding optimal treatment approaches in the unresectable/metastatic setting on account of the limited availability of high-level clinical evidence. As a result, a multidisciplinary approach to management of lung NETs is required to ensure a consistent and optimal level of care. RADIANT-4 is the first phase III trial involving a large subpopulation of patients with advanced well-differentiated lung NETs to report reductions in the risk for disease progression and death with everolimus over placebo. This led to the recent U.S. approval of everolimus-the first agent approved for advanced lung TCs/ACs. To further improve evidence-based care, additional randomized controlled trials in patients with lung carcinoids are needed. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  6. Leptin, ciliary neurotrophic factor, leukemia inhibitory factor and interleukin-6: class-I cytokines involved in the neuroendocrine regulation of the reproductive function.

    Science.gov (United States)

    Dozio, E; Ruscica, M; Galliera, E; Corsi, M M; Magni, P

    2009-12-01

    Class-I cytokines represent a large group of molecules involved in different physiological processes including host defence, immune regulation, food intake, energy metabolism and, relevant for this review, reproduction. In this latter respect, here, we focus the attention on four of these molecules, specifically leptin, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). These cytokines present similar three-dimensional fold structure, interact with related class-I receptors, which are expressed in the same regions (i.e., hypothalamus), and activate similar intracellular pathways. Leptin and CNTF share functional similarities, by acting at hypothalamic and pituitary levels, and their receptors are colocalized in the arcuate and paraventricular nuclei of the hypothalamus. For both these molecules, no effect on GnRH migration has been described. LIF has also been shown to affect gonadotropin secretion and here we present the novel observation that it is also able to stimulate GnRH secretion in vitro. Moreover, in the mouse, LIF is prenatally expressed in nasal regions where GnRH neurons originate and start their migration, and in vitro it stimulates intrinsic cell motility and directional migration. The role of the prototypical cytokine, IL-6, on the GnRH-LH axis is not fully clear and additional information seem necessary to better clarify this aspect. In conclusion, the data here discussed suggest that this family of cytokines appears to participate to the complex control of the reproductive function by affecting the development and function of the hypothalamus-pituitary system at different ontogenic times and anatomical sites.

  7. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model

    Directory of Open Access Journals (Sweden)

    Rita Azeredo

    2017-09-01

    Full Text Available Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level or a control diet meeting the amino acids requirement levels (CTRL. Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led to increased levels of plasma cortisol after the inflammatory insult, while brain monoamine content was higher in TRP-fed fish. Peripheral blood respiratory burst was higher in TRP-fed fish injected with the bacteria inoculum but only compared to those fed MET. However, no changes were detected in total antioxidant capacity. Complement factor 3 was upregulated in MET-fed fish but methionine seemed to poorly affect other genes expression patterns. In contrast, fish fed MET showed increased immune cells numbers both before and after immune challenge, suggesting a strong enhancing effect of methionine on immune cells proliferation. Differently, tryptophan effects on inflammatory transcripts suggested an inhibitory mode of action. This, together

  8. Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model.

    Science.gov (United States)

    Azeredo, Rita; Machado, Marina; Afonso, António; Fierro-Castro, Camino; Reyes-López, Felipe E; Tort, Lluis; Gesto, Manuel; Conde-Sieira, Marta; Míguez, Jesús M; Soengas, José L; Kreuz, Eva; Wuertz, Sven; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamin

    2017-01-01

    Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level) or a control diet meeting the amino acids requirement levels (CTRL). Fish were sampled for immune status assessment and the remaining fish were challenged with intraperitoneally injected inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h post-injection. Respiratory burst activity, brain monoamines, plasma cortisol, and immune-related gene expression showed distinct and sometimes opposite patterns regarding the effects of dietary amino acids. While neuroendocrine intermediates were not affected by any dietary treatment at the end of the feeding trial, both supplemented diets led to increased levels of plasma cortisol after the inflammatory insult, while brain monoamine content was higher in TRP-fed fish. Peripheral blood respiratory burst was higher in TRP-fe