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Sample records for neuroendocrine reproductive axis

  1. The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).

    Science.gov (United States)

    Wolfe, Andrew; Divall, Sara; Wu, Sheng

    2014-10-01

    The mammalian reproductive hormone axis regulates gonadal steroid hormone levels and gonadal function essential for reproduction. The neuroendocrine control of the axis integrates signals from a wide array of inputs. The regulatory pathways important for mediating these inputs have been the subject of numerous studies. One class of proteins that have been shown to mediate metabolic and growth signals to the CNS includes Insulin and IGF-1. These proteins are structurally related and can exert endocrine and growth factor like action via related receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction has been studied extensively. This review summarizes the in vitro and in vivo models that have been used to study these neuroendocrine structures and the influence of these growth factors on neuroendocrine control of reproduction. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Defining global neuroendocrine gene expression patterns associated with reproductive seasonality in fish.

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    Dapeng Zhang

    Full Text Available BACKGROUND: Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning, sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h typical of the springtime breeding season (May, we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABA(A gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. CONCLUSIONS/SIGNIFICANCE: Using both

  3. Neuroendocrine causes of amenorrhea--an update.

    Science.gov (United States)

    Fourman, Lindsay T; Fazeli, Pouneh K

    2015-03-01

    Secondary amenorrhea--the absence of menses for three consecutive cycles--affects approximately 3-4% of reproductive age women, and infertility--the failure to conceive after 12 months of regular intercourse--affects approximately 6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception.

  4. Neuroendocrine Causes of Amenorrhea—An Update

    Science.gov (United States)

    Fourman, Lindsay T.

    2015-01-01

    Context: Secondary amenorrhea—the absence of menses for three consecutive cycles—affects approximately 3–4% of reproductive age women, and infertility—the failure to conceive after 12 months of regular intercourse—affects approximately 6–10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. PMID:25581597

  5. Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility.

    Science.gov (United States)

    Navarro, Victor M; Tena-Sempere, Manuel

    2011-09-13

    The neurohormonal control of reproduction involves a hierarchical network of central and peripheral signals in the hypothalamic-pituitary-gonadal (HPG) axis. Development and function of this neuroendocrine system is the result of a lifelong delicate balance between endogenous regulators and environmental cues, including nutritional and metabolic factors. Kisspeptins are the peptide products of KISS1, which operate via the G-protein-coupled receptor GPR54 (also known as Kiss1R). These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the HPG axis. They are potent elicitors of gonadotropin secretion in various species and physiological settings. Moreover, Kiss1 neurons in the hypothalamus participate in crucial features of reproductive maturation and function, such as brain-level sex differentiation, puberty onset and the neuroendocrine regulation of gonadotropin secretion and ovulation. Cotransmitters of Kiss1 neurons, such as neurokinin B, with roles in controlling the HPG axis have been identified by genetic, neuroanatomical and physiological studies. In addition, a putative role has been proposed for Kiss1 neurons in transmitting metabolic information to GnRH neurons, although the precise mechanisms are as yet unclear. In this Review, we present the major reproductive features of kisspeptins, especially their interplay with neurokinin B and potential roles in the metabolic control of puberty and fertility, and suggest new avenues for research.

  6. ROLE OF SEROTONIN IN FISH REPRODUCTION

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    Parvathy ePrasad

    2015-06-01

    Full Text Available The neuroendocrine mechanism regulates reproduction through the hypothalamo-pituitary-gonadal (HPG axis which is evolutionarily conserved in vertebrates. The HPG axis is regulated by a variety of internal as well as external factors. Serotonin, a monoamine neurotransmitter, is involved in a wide range of reproductive functions. In mammals, serotonin regulates sexual behaviours, gonadotropin release and gonadotropin-release hormone (GnRH secretion. However, the serotonin system in teleost may play unique role in the control of reproduction as the mechanism of reproductive control in teleosts is not always the same as in the mammalian models. In fish, the serotonin system is also regulated by natural environmental factors as well as chemical substances. In particular, selective serotonin reuptake inhibitors (SSRIs are commonly detected as pharmaceutical contaminants in the natural environment. Those factors may influence fish reproductive functions via the serotonin system. This review summarizes the functional significance of serotonin in the teleosts reproduction.

  7. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

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    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  8. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

    2014-01-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  9. Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

    Science.gov (United States)

    Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Morano, Francesca; Zanuy, Silvia; Muñoz-Cueto, José A

    2016-06-01

    Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide. © 2016 by the Society for the Study of Reproduction, Inc.

  10. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

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    Tessa K Solomon-Lane; Erica J Crespi; Erica J Crespi; Matthew Scott Grober; Matthew Scott Grober

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has ...

  11. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change

    OpenAIRE

    Solomon-Lane, Tessa K.; Crespi, Erica J.; Grober, Matthew S.

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has be...

  12. Chronobiology of reproduction in garter snakes: neuroendocrine mechanisms and geographic variation.

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    Lutterschmidt, Deborah I

    2012-05-01

    The majority of studies on reproductive neuroendocrinology in snakes have focused on one particular snake population in Manitoba, Canada, the red-sided garter snake (Thamnophis sirtalis parietalis). Although traditionally these studies have emphasized its unusual temporal dissociation between mating behavior and peak gonadal activity, current evidence suggests that reproductive regulation in this population may be more similar to the norm than previously thought. Like other ectotherms, temperature plays a critical role in activating reproductive behavior in red-sided garter snakes. Diel melatonin and corticosterone rhythms appear to be important in transducing temperature cues, and it is clear that both hormones regulate courtship behavior during spring. Current evidence also suggests that sex steroid hormones are in fact central to reproductive regulation in males, although the timing of their action occurs during winter dormancy. Whether this is also true for female T. sirtalis parietalis requires further study, but it should be noted that patterns of sex steroid hormones are sexually dimorphic during winter dormancy, as are melatonin rhythms during spring emergence. While continuing to advance our understanding of reproductive regulation in this extremely well-studied population is prudent, future comparative studies are critical for understanding if and how reproductive regulatory mechanisms differ across environments, populations, and phylogenies. For example, melatonin and corticosterone responses to environmental cues vary significantly among populations of T. sirtalis in a common garden, as do male courtship behavior and androgen concentrations. These data support the hypothesis that neuroendocrine-mediated responses to environmental cues underlie phenotypic plasticity in reproductive life history traits. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Reproductive neuroendocrine pathways of social behavior

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    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.

  14. Neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn. leaf in male Wistar rat model of cyclophosphamide-induced reproductive toxicity

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    Oladele Abiodun Ayoka

    Full Text Available Cyclophosphamide (CP is a widely used cytotoxic alkylating agent with antitumor and immunosuppressant properties that is associated with various forms of reproductive toxicity. The significance of natural antioxidants of plant origin should be explored, especially in a world with increasing incidence of patients in need of chemotherapy. The neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn. leaf (AEAVL in Wistar rats with CP-induced reproductive toxicity was determined. Forty rats were used for this study such that graded doses of the extract were administered following CP-induced reproductive toxicity and comparisons were made against control, toxic and standard (vitamin E groups at p < 0.05. The synthetic drugs (CP, 65 mg/kg i.p. for 5 days; Vitamin E, 100 mg/kg p.o. for 30 days as well as the extract (100, 200 and 400 mg/kg p.o. for 30 days were administered to the rats at 0.2 mL/100 g. CP induced reproductive toxicity as evidenced by significantly lowered levels of FSH, LH and testosterone, perturbation of sperm characterization, deleterious disruptions of the antioxidant system as evidenced by decreased levels of GSH as well as elevation of TBARS activity. Histopathological examination showed hemorrhagic lesions with scanty and hypertrophied parenchymal cells in the pituitary while the testis showed ballooned seminiferous tubules with loosed connective tissues and vacuolation of testicular interstitium. These conditions were significantly reversed (p < 0.05 following administration of the graded doses of the extract. It was, therefore, concluded that AEAVL could potentially be a therapeutic choice in patients with CP-induced neuro-endocrine dysfunction and reproductive toxicity. Keywords: Cyclophosphamide, Neuro-endocrine dysfunction, Reproductive toxicity, Rats, Amaranthus viridis

  15. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

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    Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  16. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    International Nuclear Information System (INIS)

    Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

    2012-01-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  17. Neuroendocrine profiles associated with discrete behavioural variation in Symphodus ocellatus, a species with male alternative reproductive tactics.

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    Nugent, B M; Stiver, K A; Alonzo, S H; Hofmann, H A

    2016-10-01

    The molecular mechanisms underlying phenotypic plasticity are not well understood. Identifying mechanisms underlying alternative reproductive tactics (ARTs) in species for which the behavioural and fitness consequences of this variation are well characterized provides an opportunity to integrate evolutionary and mechanistic understanding of the maintenance of variation within populations. In the ocellated wrasse Symphodus ocellatus, the behavioural phenotypes of three distinct male morphs (sneakers, satellites and nesting males), which arise from a single genome, have been thoroughly characterized. To determine the neuroendocrine and genomic mechanisms associated with discrete phenotypic variation and ARTs in S. ocellatus in their natural environment, we constructed a whole-brain de novo transcriptome and compared global patterns of gene expression between sexes and male morphs. Next, we quantified circulating cortisol and 11-ketotestosterone (11-kt), mediators of male reproductive behaviours, as well as stress and gonadal steroid hormone receptor expression in the preoptic area, ventral subpallial division of the telencephalon and dorsolateral telencephalon, critical brain regions for social and reproductive behaviours. We found higher levels of 11-kt in nesting males and higher levels of cortisol in sneaker males relative to other male morphs and females. We also identified distinct patterns of brain region-specific hormone receptor expression between males such that most hormone receptors are more highly expressed in satellites and nesting males relative to sneakers and females. Our results establish the neuroendocrine and molecular mechanisms that underlie ARTs in the wild and provide a foundation for experimentally testing hypotheses about the relationship between neuromolecular processes and reproductive success. © 2016 John Wiley & Sons Ltd.

  18. 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

  19. Steroidogenic versus Metabolic Programming of Reproductive Neuroendocrine, Ovarian and Metabolic Dysfunctions.

    Science.gov (United States)

    Cardoso, Rodolfo C; Puttabyatappa, Muraly; Padmanabhan, Vasantha

    2015-01-01

    The susceptibility of the reproductive system to early exposure to steroid hormones has become a major concern in our modern societies. Human fetuses are at risk of abnormal programming via exposure to endocrine disrupting chemicals, inadvertent use of contraceptive pills during pregnancy, as well as from excess exposure to steroids due to disease states. Animal models provide an unparalleled resource to understand the developmental origin of diseases. In female sheep, prenatal exposure to testosterone excess results in an array of adult reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary sensitivity to gonadotropin-releasing hormone, luteinizing hormone excess, functional hyperandrogenism, and multifollicular ovarian morphology culminating in early reproductive failure. Prenatal testosterone treatment also leads to fetal growth retardation, insulin resistance, and hypertension. Mounting evidence suggests that developmental exposure to an improper steroidal/metabolic environment may mediate the programming of adult disorders in prenatal testosterone-treated females, and these defects are maintained or amplified by the postnatal sex steroid and metabolic milieu. This review addresses the steroidal and metabolic contributions to the development and maintenance of the PCOS phenotype in the prenatal testosterone-treated sheep model, including the effects of prenatal and postnatal treatment with an androgen antagonist or insulin sensitizer as potential strategies to prevent/ameliorate these dysfunctions. Insights obtained from these intervention strategies on the mechanisms underlying these defects are likely to have translational relevance to human PCOS. © 2015 S. Karger AG, Basel.

  20. The impact of reproduction on the stress axis of free-living male northern red backed voles (Myodes rutilus).

    Science.gov (United States)

    Fletcher, Quinn E; Dantzer, Ben; Boonstra, Rudy

    2015-12-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis culminates in the release of glucocorticoids (henceforth CORT), which have wide-reaching physiological effects. Three hypotheses potentially explain seasonal variation in CORT. The enabling hypothesis predicts that reproductive season CORT exceeds post-reproductive season CORT because CORT enables reproductive investment. The inhibitory hypothesis predicts the opposite because CORT can negatively affect reproductive function. The costs of reproduction hypothesis predicts that HPA axis condition declines over and following the reproductive season. We tested these hypotheses in wild male red-backed voles (Myodes rutilus) during the reproductive and post-reproductive seasons. We quantified CORT levels in response to restraint stress tests consisting of three blood samples (initial, stress-induced, and recovery). Mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA levels in the brain were also quantified over the reproductive season. Total CORT (tCORT) in the initial and stress-induced samples were greater in the post-reproductive than in the reproductive season, which supported the inhibitory hypothesis. Conversely, free CORT (fCORT) did not differ between the reproductive and post-reproductive seasons, which was counter to both the enabling and inhibitory hypotheses. Evidence for HPA axis condition decline in CORT as well as GR and MR mRNA over the reproductive season (i.e. costs of reproduction hypothesis) was mixed. Moreover, all of the parameters that showed signs of declining condition over the reproductive season did not also show signs of declining condition over the post-reproductive season suggesting that the costs resulting from reproductive investment had subsided. In conclusion, our results suggest that different aspects of the HPA axis respond differently to seasonal changes and reproductive investment. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. CXCR4/CXCL12/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR.

    Science.gov (United States)

    Circelli, Luisa; Sciammarella, Concetta; Guadagno, Elia; Tafuto, Salvatore; del Basso de Caro, Marialaura; Botti, Giovanni; Pezzullo, Luciano; Aria, Massimo; Ramundo, Valeria; Tatangelo, Fabiana; Losito, Nunzia Simona; Ieranò, Caterina; D'Alterio, Crescenzo; Izzo, Francesco; Ciliberto, Gennaro; Colao, Annamaria; Faggiano, Antongiulio; Scala, Stefania

    2016-04-05

    To evaluate the possible crosstalk between C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor 7 (CXCR7) axis with the mammalian target of rapamycin (mTOR) pathway in neuroendocrine tumors (NETs). Sixty-one human NETs were included into the study. CXCR4/CXCL12/CXCR7 axis and mTOR pathway were assessed by qRT-PCR and immunohistochemistry (IHC). The effect of mTOR inhibitor, RAD001, was evaluated on CXCR4 pathway through proliferation and p-Erk and p-AKT induction. CXCR4/CXCL12/CXCR7 axis and p-mTOR were found to be active and correlated with grading, Ki67 index and tumor stage. mTOR pathway activation significantly correlated with poor prognosis. In human NET cells, CXCL12 induced mTOR signalling while AMD3100 (CXCR4-antagonist) impaired it. The mTOR-antagonist, RAD001, impaired the CXCL12-dependent induction of CXCR4 downstream effectors. Combination of AMD3100 and RAD001 potentiate cell growth inhibition. CXCR4/CXCL12/CXCR7 axis is active in NETs and signals on mTOR. CXCR4 might be considered a prognostic factor in NETs. Combined treatment with AMD3100 and RAD001 may provide clinical benefits in NET patients with drug-resistant.

  2. Relaxin-3/RXFP3 signaling and neuroendocrine function – A perspective on extrinsic hypothalamic control

    Directory of Open Access Journals (Sweden)

    Despina E Ganella

    2013-09-01

    Full Text Available Complex neural circuits within the hypothalamus that govern essential autonomic processes and associated behaviors signal using amino acid and monoamine transmitters and a variety of neuropeptide (hormone modulators, often via G-protein coupled receptors (GPCRs and associated cellular pathways. Relaxin-3 is a recently identified neuropeptide that is highly conserved throughout evolution. Neurons expressing relaxin-3 are located in the brainstem, but broadly innervate the entire limbic system including the hypothalamus. Extensive anatomical data in rodents and non-human primate, and recent regulatory and functional data, suggest relaxin-3 signaling via its cognate GPCR, RXFP3, has a broad range of effects on neuroendocrine function associated with stress responses, feeding and metabolism, motivation and reward, and possibly sexual behavior and reproduction. Therefore, this article aims to highlight the growing appreciation of the relaxin-3/RXFP3 system as an important ‘extrinsic’ regulator of the neuroendocrine axis by reviewing its neuroanatomy and its putative roles in arousal-, stress- and feeding-related behaviors and links to associated neural substrates and signaling networks. Current evidence identifies RXFP3 as a potential therapeutic target for treatment of neuroendocrine disorders and related behavioral dysfunction.

  3. A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

    Science.gov (United States)

    Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  5. Neuroendocrine Role for VGF

    Directory of Open Access Journals (Sweden)

    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.

  6. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function.

    Science.gov (United States)

    Perakakis, Nikolaos; Upadhyay, Jagriti; Ghaly, Wael; Chen, Joyce; Chrysafi, Pavlina; Anastasilakis, Athanasios D; Mantzoros, Christos S

    2018-05-09

    We have previously demonstrated that the adipose tissue derived hormone leptin controls reproductive function by regulating the hypothalamic-pituitary-gonadal axis in response to energy deficiency. Here, we evaluate the activins-follistatins-inhibins (AFI) axis during acute (short-term fasting in healthy people) and chronic energy deficiency (women with hypothalamic amenorrhea due to strenuous exercise [HA]) and investigate their relation to leptin and reproductive function in healthy subjects and subjects with HA. The AFI axis was investigated in: a) A double-blinded study in healthy subjects having three randomly assigned admissions, each time for four days: in the isocaloric fed state, complete fasting with placebo treatment, complete fasting with leptin replacement, b) A case-control study comparing women with HA vs healthy controls, c) An open-label interventional study investigating leptin treatment in women with HA over a period of up to three months, d) A randomized interventional trial investigating leptin treatment vs placebo in women with HA for nine months. The circulating levels of activin A, activin B, follistatin and follistatin-like 3 change robustly in response to acute and chronic energy deficiency. Leptin replacement in acute energy deprivation does not affect the levels of these hormones suggesting an independent regulation by these two hormonal pathways. In chronic energy deficiency, leptin replacement restores only activin B levels, which are in turn associated with an increase in the number of dominant follicles. We demonstrate for the first time that the AFI axis is affected both by acute and chronic energy deficiency. Partial restoration of a component of the axis, i.e. activin B only, through leptin replacement is associated with improved reproductive function in women with HA. Copyright © 2018. Published by Elsevier Inc.

  7. Puberty and Perimenopause: Reproductive Transitions and their Implications for Women's Health

    Science.gov (United States)

    Hoyt, Lindsay T.; Falconi, April

    2015-01-01

    This scoping review synthesizes existing research on two major transitions in females’ lives: puberty and perimenopause. These two periods of vast physiological change demarcate the beginning and the end of the reproductive life cycle and are associated with major neuroendocrine reorganization across two key systems, the hypothalamic-pituitary-gonadal (HPG) axis the hypothalamus-pituitary-adrenal (HPA) axis. Despite growing evidence suggesting that the timing and experience of puberty and perimenopause are related to various physical and mental health outcomes (e.g., mood disorders, metabolism, cardiovascular health, autoimmune conditions and cancer), these two processes are rarely examined together. In this paper, we bridge these disparate literatures to highlight similarities, isolate inconsistencies, and identify important areas for future research in women’s health. PMID:25797100

  8. Reproduction Symposium: developmental programming of reproductive and metabolic health.

    Science.gov (United States)

    Padmanabhan, V; Veiga-Lopez, A

    2014-08-01

    Inappropriate programming of the reproductive system by developmental exposure to excess steroid hormones is of concern. Sheep are well suited for investigating developmental origin of reproductive and metabolic disorders. The developmental time line of female sheep (approximately 5 mo gestation and approximately 7 mo to puberty) is ideal for conducting sequential studies of the progression of metabolic and/or reproductive disruption from the developmental insult to manifestation of adult consequences. Major benefits of using sheep include knowledge of established critical periods to target adult defects, a rich understanding of reproductive neuroendocrine regulation, availability of noninvasive approaches to monitor follicular dynamics, established surgical approaches to obtain hypophyseal portal blood for measurement of hypothalamic hormones, and the ability to perform studies in natural setting thereby keeping behavioral interactions intact. Of importance is the ability to chronically instrument fetus and mother for determining early endocrine perturbations. Prenatal exposure of the female to excess testosterone (T) leads to an array of adult reproductive disorders that include LH excess, functional hyperandrogenism, neuroendocrine defects, multifollicular ovarian morphology, and corpus luteum dysfunction culminating in early reproductive failure. At the neuroendocrine level, all 3 feedback systems are compromised. At the pituitary level, gonadotrope (LH secretion) sensitivity to GnRH is increased. Multifollicular ovarian morphology stems from persistence of follicles as well as enhanced follicular recruitment. These defects culminate in progressive loss of cyclicity and reduced fecundity. Prenatal T excess also leads to fetal growth retardation, an early marker of adult reproductive and metabolic diseases, insulin resistance, hypertension, and behavioral deficits. Collectively, the reproductive and metabolic deficits of prenatal T-treated sheep provide proof of

  9. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Central mechanisms underlying variability in the behavioral and neuroendocrine responses to stress in fish

    DEFF Research Database (Denmark)

    Moltesen, Maria Møller

    of the stress response. In mammals, the hippocampus and amygdala in the telencephalon play central roles in the process of discriminating sensory inputs that, potentially, will threaten the homeostasis of an individual. These regions are part of the limbic system, which interacts with the hypothalamic......-pituitary-adrenal axis (HPA axis). This neuroendocrine stress axis includes corticotropin-releasing factor (CRF), which regulates the release of adrenocorticotropic hormone (ACTH) from the pituitary. A peptide is released to the circulation, inducing release of glucocorticoids from the adrenal cortex....... The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) also plays an important role in the neuroendocrine stress response by controlling CRF release in hypothalamus. The transmission of 5-HT and CRF are under feedback control of glucocorticoids and interact with the stress response by affecting processes...

  12. REPRODUCTIVE SEASONALITY OF SHEEP IN MEXICO

    Directory of Open Access Journals (Sweden)

    Jaime Arroyo

    2011-07-01

    Full Text Available In order to discuss and analyze the available information concerning the seasonal breeding behavior of sheep in Mexico, this review was conducted. We analyzed the neuroendocrine basis that modulate the annual reproductive cycle in sheep and then discussed the degree of reproductive seasonality in Creole sheep wool, breeds originating in high latitudes and hair sheep, mainly in Pelibuey ewes. The Creole sheep wool show continuous annual reproductive activity and short seasonal anestrous. The females of northern origin, express seasonal reproductive activity, similar to that observed in individuals geographically located at latitudes above 35º. Pelibuey sheep show variable annual reproductive behavior with reduced anestrus or lack thereof.  It is suggested that the neuroendocrine mechanisms regulating seasonal anestrus in ewes, are active in the sheep of northern origin that live in Mexico, in a manner contrary is not activated in Creole and hair sheep.

  13. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, A D; Lanzoni, C; Ricchieri, F; Santagni, S; Rattighieri, E; Chierchia, E; Monteleone, P; Jasonni, V M

    2011-04-01

    Hypothalamic amenorrhea (HA) is characterized by neuroendocrine impairment that, in turn, negatively modulates endocrine function, mainly within the reproductive axis. HA presents with hypo-LH, hypoestrogenism and, until now, a definite therapeutic strategy has not yet been found. The aim of the following study was to test the efficacy of acetyl-L-carnitine (ALC) administration in HA-affected subjects. Twenty-four patients affected by stress-induced HA were divided into two groups according to LH plasma levels: group A, hypo-LH (LH≤3 mIU/ml; no.=16), and group B, normo-LH (LH>3 mIU/ml; no.=8), were treated with ALC (1 g/day, per os) for 16 weeks. Patients underwent baseline hormonal assessment, pulsatility test (for LH and FSH), naloxone test (for LH, FSH and cortisol) both before and after 16 weeks of treatment. Under ALC administration hypo-LH patients showed a significant increase in LH plasma levels (from 1.4±0.3 to 3.1±0.5 mIU/ml, p<0.01) and in LH pulse amplitude (p<0.001). No changes were observed in the normo-LH group. LH response to naloxone was restored under ALC therapy. Maximal LH response and area under the curve under naloxone were significantly increased (p<0.05 and p<0.01, respectively). No changes were observed in the normo-LH patients. Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea.

  14. Neuroendocrine regulation of appetitive ingestive behavior

    OpenAIRE

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E.

    2013-01-01

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endo...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Reproductive Hormones and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2010-12-01

    Full Text Available During the menstrual cycle, pregnancy and breast-feeding periods, as well as in menopausal and post-menopausal periods, the physiological and psychological processes that change according to the hormonal fluctuations influence every women similarly and each one differently. These physiological processes are controlled by neuroendocrine sequences, of which the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis are the most important ones. The hypothalamo-pituitary-gonadal axis affects mood, anxiety, cognition and pain. The interaction of these hormones with mood and behavior is bidirectional. The differences in phenomenology and epidemiology of mood disorders with regards to gender can be explained with the effects of hormones. All of the periods mentioned above are related with mood disorders at terms of risk factors, disease symptoms, progress of disease and response to treatment. Epidemiologic data supports the relationship between the mood disorders and reproductive processes. The prevalence of major depression increases in women with the menarche and ceases in post- menopausal period. Similarly, the initial symptoms of bipolar disorder begins around the menarche period in 50% of the cases. Despite proper treatment, some female patients with major depression experience recurrence during the premenstrual period of their menstrual cycles. The conformity and change in a woman’s brain during pregnancy is controlled dominantly by the neuroendocrine systems, while it is controlled by the external stimuli actively related to the baby during nursing period. The changes that occur are closely related to postpartum mood disorders. Again, all the changes and suspension of medication during this procedure are risk factors for early depressive and dysphoric situations. Variables of a wide range, from follicle stimulating hormone, melatonin, and sleep to body mass index interact with mood disorders in menopausal and post

  17. Photoperiodic Modulation of Circadian Clock and Reproductive Axis Gene Expression in the Pre-Pubertal European Sea Bass Brain.

    Directory of Open Access Journals (Sweden)

    Rute S T Martins

    Full Text Available The acquisition of reproductive competence requires the activation of the brain-pituitary-gonad (BPG axis, which in most vertebrates, including fishes, is initiated by changes in photoperiod. In the European sea bass long-term exposure to continuous light (LL alters the rhythm of reproductive hormones, delays spermatogenesis and reduces the incidence of precocious males. In contrast, an early shift from long to short photoperiod (AP accelerates spermatogenesis. However, how photoperiod affects key genes in the brain to trigger the onset of puberty is still largely unknown. Here, we investigated if the integration of the light stimulus by clock proteins is sufficient to activate key genes that trigger the BPG axis in the European sea bass. We found that the clock genes clock, npas2, bmal1 and the BPG genes gnrh, kiss and kissr share conserved transcription factor frameworks in their promoters, suggesting co-regulation. Other gene promoters of the BGP axis were also predicted to be co-regulated by the same frameworks. Co-regulation was confirmed through gene expression analysis of brains from males exposed to LL or AP photoperiod compared to natural conditions: LL fish had suppressed gnrh1, kiss2, galr1b and esr1, while AP fish had stimulated npas2, gnrh1, gnrh2, kiss2, kiss1rb and galr1b compared to NP. It is concluded that fish exposed to different photoperiods present significant expression differences in some clock and reproductive axis related genes well before the first detectable endocrine and morphological responses of the BPG axis.

  18. Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.

    Science.gov (United States)

    Zhou, Dongsheng; Zhuo, Yong; Che, Lianqiang; Lin, Yan; Fang, Zhengfeng; Wu, De

    2014-07-01

    People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.

  19. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction.

    Science.gov (United States)

    Bellefontaine, Nicole; Chachlaki, Konstantina; Parkash, Jyoti; Vanacker, Charlotte; Colledge, William; d'Anglemont de Tassigny, Xavier; Garthwaite, John; Bouret, Sebastien G; Prevot, Vincent

    2014-06-01

    The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region.

  20. Effects of global warming on fish reproductive endocrine axis, with special emphasis in pejerrey Odontesthes bonariensis.

    Science.gov (United States)

    Miranda, Leandro Andrés; Chalde, Tomás; Elisio, Mariano; Strüssmann, Carlos Augusto

    2013-10-01

    The ongoing of global warming trend has led to an increase in temperature of several water bodies. Reproduction in fish, compared with other physiological processes, only occurs in a bounded temperature range; therefore, small changes in water temperature could significantly affect this process. This review provides evidence that fish reproduction may be directly affected by further global warming and that abnormal high water temperature impairs the expression of important genes throughout the brain-pituitary-gonad axis. In all fishes studied, gonads seem to be the organ more readily damaged by heat treatments through the inhibition of the gene expression and subsequent synthesis of different gonadal steroidogenic enzymes. In view of the feedback role of sex steroids upon the synthesis and release of GnRH and GtHs in fish, it is possible that the inhibition observed at brain and pituitary levels in treated fish is consequence of the sharp decrease in plasma steroids levels. Results of in vitro studies on the inhibition of pejerrey gonad aromatase expression by high temperature corroborate that ovary functions are directly disrupted by high temperature independently of the brain-pituitary axis. For the reproductive responses obtained in laboratory fish studies, it is plausible to predict changes in the timing and magnitude of reproductive activity or even the total failure of spawning season may occur in warm years, reducing annual reproductive output and affecting future populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

    Science.gov (United States)

    Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

    2017-08-01

    Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

  2. Stress and the hypothalamus-pituitary-gonadal axis in the cyclic rat

    NARCIS (Netherlands)

    Roozendaal, M.M.

    1997-01-01


    The influence of stress on reproductive functions has been subject of much research. Various kinds of stress are known to affect reproductive functions. In females, the complex regulation of the ovarian cycle relies on a series of neuroendocrine events whose temporal relationship is so

  3. Insulin: its role in the central control of reproduction.

    Science.gov (United States)

    Sliwowska, Joanna H; Fergani, Chrysanthi; Gawałek, Monika; Skowronska, Bogda; Fichna, Piotr; Lehman, Michael N

    2014-06-22

    Insulin has long been recognized as a key regulator of energy homeostasis via its actions at the level of the brain, but in addition, plays a role in regulating neural control of reproduction. In this review, we consider and compare evidence from animal models demonstrating a role for insulin for physiological control of reproduction by effects on GnRH/LH secretion. We also review the role that insulin plays in prenatal programming of adult reproduction, and consider specific candidate neurons in the adult hypothalamus by which insulin may act to regulate reproductive function. Finally, we review clinical evidence of the role that insulin may play in adult human fertility and reproductive disorders. Overall, while insulin appears to have a significant impact on reproductive neuroendocrine function, there are many unanswered questions regarding its precise sites and mechanisms of action, and their impact on developing and adult reproductive neuroendocrine function. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Effects of pinealectomy on the neuroendocrine reproductive system and locomotor activity in male European sea bass, Dicentrarchus labrax.

    Science.gov (United States)

    Cowan, Mairi; Paullada-Salmerón, José A; López-Olmeda, José Fernando; Sánchez-Vázquez, Francisco Javier; Muñoz-Cueto, José A

    2017-05-01

    The seasonally changing photoperiod controls the timing of reproduction in most fish species, however, the transduction of this photoperiodic information to the reproductive axis is still unclear. This study explored the potential role of two candidate neuropeptide systems, gonadotropin-inhibitory hormone (Gnih) and kisspeptin, as mediators between the pineal organ (a principle transducer of photoperiodic information) and reproductive axis in male European sea bass, Dicentrarchus labrax. Two seven-day experiments of pinealectomy (Px) were performed, in March (end of reproductive season) and August (resting season). Effects of Px and season on the brain expression of gnih (sbgnih) and its receptor (sbgnihr), kisspeptins (kiss1, kiss2) and their receptors (kissr2, kissr3) and gonadotropin-releasing hormone (gnrh1, gnrh2, gnrh3) and the main brain receptor (gnrhr-II-2b) genes, plasma melatonin levels and locomotor activity rhythms were examined. Results showed that Px reduced night-time plasma melatonin levels. Gene expression analyses demonstrated a sensitivity of the Gnih system to Px in March, with a reduction in sbgnih in the mid-hindbrain, a region with bilateral connections to the pineal organ. In August, kiss2 levels increased in Px animals but not in controls. Significant differences in expression were observed for diencephalic sbgnih, sbgnihr, kissr3 and tegmental gnrh2 between seasons. Recordings of locomotor activity following surgery revealed a change from light-synchronised to free-running rhythmic behavior. Altogether, the Gnih and Kiss2 sensitivity to Px and seasonal differences observed for Gnih and its receptor, Gnrh2, and the receptor for Kiss2 (Kissr3), suggested they could be mediators involved in the relay between environment and seasonal reproduction. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Stress and its influence on reproduction in pigs: a review

    Directory of Open Access Journals (Sweden)

    Madej Andrzej

    2008-12-01

    Full Text Available Abstract The manifestations of stress, defined as a biological response to an event that the individual perceives as a threat to its homeostasis, are commonly linked to enhanced activity of the hypothalamo-pituitary-adrenal (HPA axis and the activation of the sympathetic adreno-medullary (SA system. Activation of the HPA system results in the secretion of peptides from the hypothalamus, principally corticotropin releasing hormone (CRH, which stimulates the release of adrenocorticotropic hormone (ACTH and beta-endorphin. ACTH induces the secretion of corticosteroids from the adrenal cortex, which can be seen in pigs exposed to acute physical and/or psychological stressors. The present paper is a review of studies on the influence of stressors on reproduction in pigs. The effects of stress on reproduction depend on the critical timing of stress, the genetic predisposition to stress, and the type of stress. The effect of stress on reproduction is also influenced by the duration of the responses induced by various stressors. Prolonged or chronic stress usually results in inhibition of reproduction, while the effects of transient or acute stress in certain cases is stimulatory (e.g. anoestrus, but in most cases is of impairment for reproduction. Most sensitive of the reproductive process are ovulation, expression of sexual behaviour and implantation of the embryo, since they are directly controlled by the neuroendocrine system.

  6. Chronic Stress and Limbic-Hypothalamopituitary-Adrenal Axis (LHPA Response in Female Reproductive system

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2009-12-01

    Full Text Available The hypothalamo-pituitary-adrenocortical (HPA axis is a critical adaptive system that maximizes survival potential in the face of physical or psychological challenge. The principal end products of the HPA axis, glucocorticoid hormones, act on multiple organ systems, including the brain, to maintain homeostatic balance. The brain is a target of stress, and the hippocampus is the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. These anatomical areas in brain are limbic system, and in particular the hippocampus, medial prefrontal cortex (mPFC and amigdal that have multiple control points in regulation of the hypothalamic–pituitary–adrenal (HPA axis. The studies show the prefrontal cortex (PFC plays an important role in the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA activity and regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classic feedback mechanisms in the hypothalamus and pituitary gland. Chronic stress can have a deleterious effect on the reproductive axis that, for females, is manifested in reduced pulsatile gonadotropin secretion and increased incidence of ovulatory abnormalities and infertility. The limbic–hypothalamic–pituitary–adrenal (LHPA axis suggests a functional role for gonadal steroids in the regulation of a female’s response to stress.

  7. A conserved non-reproductive GnRH system in chordates.

    Directory of Open Access Journals (Sweden)

    Takehiro G Kusakabe

    Full Text Available Gonadotropin-releasing hormone (GnRH is a neuroendocrine peptide that plays a central role in the vertebrate hypothalamo-pituitary axis. The roles of GnRH in the control of vertebrate reproductive functions have been established, while its non-reproductive function has been suggested but less well understood. Here we show that the tunicate Ciona intestinalis has in its non-reproductive larval stage a prominent GnRH system spanning the entire length of the nervous system. Tunicate GnRH receptors are phylogenetically closest to vertebrate GnRH receptors, yet functional analysis of the receptors revealed that these simple chordates have evolved a unique GnRH system with multiple ligands and receptor heterodimerization enabling complex regulation. One of the gnrh genes is conspicuously expressed in the motor ganglion and nerve cord, which are homologous structures to the hindbrain and spinal cord of vertebrates. Correspondingly, GnRH receptor genes were found to be expressed in the tail muscle and notochord of embryos, both of which are phylotypic axial structures along the nerve cord. Our findings suggest a novel non-reproductive role of GnRH in tunicates. Furthermore, we present evidence that GnRH-producing cells are present in the hindbrain and spinal cord of the medaka, Oryzias latipes, thereby suggesting the deep evolutionary origin of a non-reproductive GnRH system in chordates.

  8. Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: Computational Modeling

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC)...

  9. Evidence of reproductive disruption associated with neuroendocrine changes induced by UV–B filters, phtalates and nonylphenol during sexual maturation in rats of both gender

    International Nuclear Information System (INIS)

    Ponzo, Osvaldo J.; Silvia, Carbone

    2013-01-01

    Endocrine disruptors (EDs) are exogenous substances or xenoestrogens natural or synthetic, capable of interacting with different systems and altering their normal hormonal regulation, being the reproductive system one of the most affected. EDs produce their effects not only by acting on nuclear steroid receptors, but also on membrane receptors, steroidal and non-steroidal synthetic enzymatic pathways and/or metabolism. The incorporation to the body depend on each EDs, which are liposoluble and easily deposited in the tissue; thus ensuring a prolonged accumulation and release, even when the exposure is not continuous. In addition to cross the placenta, EDs may act in the offspring during the reproductive system formation and maturation key stages and its regulatory mechanisms. The effects of EDs can be multiple, but most acts mediating estrogenic and/or antiandrogenic effect. Three groups of EDs are widely used: in plastics (phtalates), sunscreens (cinnamate and methylbenzylcamphor), and detergents (nonylphenol). In this paper we review the effects of the exposure to these environmental chemicals on the reproductive system and the possible mechanisms by which they occur, focusing in the hypothalamic–pituitary neuroendocrine mechanisms that regulate the reproductive system

  10. Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis.

    Directory of Open Access Journals (Sweden)

    Sushil Kumar

    Full Text Available Nutritional infertility is very common in societies where women fail to eat enough to match their energy expenditure and such females often present as clinical cases of anorexia nervosa. The cellular and molecular mechanisms that link energy balance and central regulation of reproduction are still not well understood. Peripheral hormones such as estradiol, testosterone and leptin, as well as neuropeptides like kisspeptin and neuropeptides Y (NPY play a potential role in regulation of reproduction and energy balance with their primary target converging on the hypothalamic median eminence-arcuate region. The present study was aimed to explore the effects of negative energy state resulting from intermittent fasting dietary restriction (IF-DR regimen on complete hypothalamo-hypophysial-gonadal axis in Wistar strain young female and male rats. Significant changes in body weight, blood glucose, estrous cyclicity and serum estradiol, testosterone and LH level indicated the negative role of IF-DR regimen on reproduction in these young animals. Further, it was elucidated whether serum level of metabolic hormone, leptin plays a mechanistic role in suppressing hypothalamo-hypophysial-gonadal (HPG axis via energy regulators, kisspeptin and NPY in rats on IF-DR regimen. We also studied the effect of IF-DR regimen on structural remodeling of GnRH axon terminals in median eminence region of hypothalamus along with the glial cell marker, GFAP and neuronal plasticity marker, PSA-NCAM using immunostaining, Western blotting and RT-PCR. Together these data suggest that IF-DR regimen negatively influences reproduction in young animals due to its adverse effects on complete hypothalamus-hypophysial-gonadal axis and may explain underlying mechanism(s to understand the clinical basis of nutritional infertility.

  11. Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis.

    Science.gov (United States)

    Kumar, Sushil; Kaur, Gurcharan

    2013-01-01

    Nutritional infertility is very common in societies where women fail to eat enough to match their energy expenditure and such females often present as clinical cases of anorexia nervosa. The cellular and molecular mechanisms that link energy balance and central regulation of reproduction are still not well understood. Peripheral hormones such as estradiol, testosterone and leptin, as well as neuropeptides like kisspeptin and neuropeptides Y (NPY) play a potential role in regulation of reproduction and energy balance with their primary target converging on the hypothalamic median eminence-arcuate region. The present study was aimed to explore the effects of negative energy state resulting from intermittent fasting dietary restriction (IF-DR) regimen on complete hypothalamo-hypophysial-gonadal axis in Wistar strain young female and male rats. Significant changes in body weight, blood glucose, estrous cyclicity and serum estradiol, testosterone and LH level indicated the negative role of IF-DR regimen on reproduction in these young animals. Further, it was elucidated whether serum level of metabolic hormone, leptin plays a mechanistic role in suppressing hypothalamo-hypophysial-gonadal (HPG) axis via energy regulators, kisspeptin and NPY in rats on IF-DR regimen. We also studied the effect of IF-DR regimen on structural remodeling of GnRH axon terminals in median eminence region of hypothalamus along with the glial cell marker, GFAP and neuronal plasticity marker, PSA-NCAM using immunostaining, Western blotting and RT-PCR. Together these data suggest that IF-DR regimen negatively influences reproduction in young animals due to its adverse effects on complete hypothalamus-hypophysial-gonadal axis and may explain underlying mechanism(s) to understand the clinical basis of nutritional infertility.

  12. Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition II: Computational Modeling

    Science.gov (United States)

    ABSTRACT Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic­ pituitary-gonadal (HPG) axis in female fathead minnows to predic...

  13. Neuroendocrine regulation of appetitive ingestive behavior

    Directory of Open Access Journals (Sweden)

    Erin eKeen-Rhinehart

    2013-11-01

    Full Text Available Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e. food stored for future consumption and endogenous (i.e. body fat stores fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g. foraging, food hoarding, and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing. Quantifiable appetitive behaviors are part of many the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as NPY, AgRP and alpha-MSH, to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the neuroendocrine regulation of the motivation to engage in ingestive

  14. Neuroendocrine changes upon exposure to predator odors.

    Science.gov (United States)

    Hegab, Ibrahim M; Wei, Wanhong

    2014-05-28

    Predator odors are non-intrusive and naturalistic stressors of high ethological relevance in animals. Upon exposure to a predator or its associated cues, robust physiological and molecular anti-predator defensive strategies are elicited thereby allowing prey species to recognize, avoid and defend against a possible predation threat. In this review, we will discuss the nature of neuroendocrine stress responses upon exposure to predator odors. Predator odors can have a profound effect on the endocrine system, including activation of the hypothalamic-pituitary-adrenal axis, and induction of stress hormones such as corticosterone and adrenocorticotropic hormone. On a neural level, short-term exposure to predator odors leads to induction of the c-fos gene, while induction of ΔFosB in a different brain region is detected under chronic predation stress. Future research should aim to elucidate the relationships between neuroendocrine and behavioral outputs to gage the different levels of anti-predator responses in prey species. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Chapter 11.18 - Neuroendocrine Control of Female Reproduction.

    Science.gov (United States)

    The hypothalamus and pituitary are known to play roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently the endocrine control of ...

  16. Reproduction, Smell and Neurodevelopmental disorders: Genetic defects in different hypogonadotropic hypogonadal syndromes.

    Directory of Open Access Journals (Sweden)

    Hernan G VALDES-SOCIN

    2014-07-01

    Full Text Available The neuroendocrine control of reproduction in mammals is governed by a neural hypothalamic network of nearly 1500 gonadotropin-releasing hormone (GnRH secreting neurons that modulate the activity of the reproductive axis across life. Congenital hypogonadotropic hypogonadism (HH is a clinical syndrome that is characterized by partial or complete pubertal failure. HH may result from inadequate hypothalamic GnRH axis activation, or a failure of pituitary gonadotropin secretion/effects. In man, several genes that participate in olfactory and GnRH neuronal migration are thought to interact during the embryonic life. A growing number of mutations in different genes are responsible for congenital HH. Based on the presence or absence of olfaction dysfunction, HH is divided in two syndromes: HH with olfactory alterations (Kallmann syndrome and idiopathic hypogonadotropic hypogonadism (IHH with normal smell (normosmic IHH. Kallmann syndrome (KS is a heterogeneous disorder affecting 1 in 5000 males, with a 3-5 fold of males over females. KS is associated with mutations in KAL1, FGFR1/FGF8, FGF17, IL17RD, PROK2/PROKR2, NELF, CHD7, HS6ST1, FLRT3, SPRY4, DUSP6, SEMA3A, NELF and WDR11 genes that are related to defects in neuronal migration. These reproductive and olfactory deficits include a variable non reproductive phenotype, including sensorineural deafness, coloboma, bimanual synkinesis, craniofacial abnormalities and/or renal agenesis. Interestingly, defects in PROKR2, FGFR1, FGF8, CHD7, DUSP6, and WDR11 genes are also associated with normosmic IHH, whereas mutations in KISS1/KISSR, TAC3/TACR3, GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB and LHB are only present in patients with normosmic IHH. In this paper, we summarize the reproductive, neurodevelopmental and genetic aspects of HH in human pathology.

  17. Neuroendocrine regulation of appetitive ingestive behavior.

    Science.gov (United States)

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E

    2013-11-15

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endogenous (i.e., body fat stores) fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g., foraging, food hoarding), and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing). Quantifiable appetitive behaviors are part of the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as neuropeptide Y (NPY), agouti-related protein (AgRP) and α-melanocyte stimulating hormone (α-MSH), to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the

  18. Developmental programming of reproductive and metabolic health1,2

    Science.gov (United States)

    Padmanabhan, V.; Veiga-Lopez, A.

    2014-01-01

    The inappropriate programming of the reproductive system by developmental exposure to excess steroid hormones is of concern. Sheep are well suited for investigating developmental origin of reproductive and metabolic disorders. The developmental time line of female sheep (~5 mo gestation and ~7 mo to puberty) is ideal for conducting sequential studies of the progression of metabolic and (or) reproductive disruption from the developmental insult to manifestation of adult consequences. Major benefits of using sheep include knowledge of established critical periods to target adult defects, a rich understanding of reproductive neuroendocrine regulation, availability of non-invasive approaches to monitor follicular dynamics, established surgical approaches to obtain hypophyseal portal blood for measurement of hypothalamic hormones, and the ability to perform studies in natural setting keeping behavioral interactions intact. Of importance is the ability to chronically instrument fetus and mother for determining early endocrine perturbations. Prenatal exposure of the female to excess testosterone (T) leads to an array of adult reproductive disorders that include LH excess, functional hyperandrogenism, neuroendocrine defects, multifollicular ovarian morphology, and corpus luteum dysfunction culminating in early reproductive failure. At the neuroendocrine level all three feedback systems are compromised. At the pituitary level, gonadotrope (LH secretion) sensitivity to GnRH is increased. Multifollicular ovarian morphology stems from persistence of follicles, as well as enhanced follicular recruitment. These defects culminate in progressive loss of cyclicity and reduced fecundity. Prenatal T excess also leads to fetal growth retardation, an early marker of adult reproductive/metabolic diseases, insulin resistance, hypertension and behavioral deficits. Collectively, the reproductive and metabolic deficits of prenatal T-treated sheep provide proof of concept for the

  19. The hypothalamo-pituitary-adrenal axis in major affective disorder

    DEFF Research Database (Denmark)

    Christensen, M V; Kessing, L V

    2001-01-01

    disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only......This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

  20. Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

    Science.gov (United States)

    Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

    2017-12-01

    A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

  1. 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

  2. Stress and Female Reproductive System: Disruption of Corticotropin-Releasing Hormone/Opiate Balance by Sympathetic Nerve Traffic

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2009-09-01

    Full Text Available Nowadays stress is an integral part of everyday living and the physiological and behavioral consequences of exposure to stressful situations have been extensively studied for decades. The stress response is a necessary mechanism but disrupts homeostatic process and it is sub served by a complex system located in both the central nervous system (CNS and the periphery. Stressor-induced activation of the hypothalamus–pituitary–adrenal (HPA axis and the sympathetic nervous system (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. Normal activation of the HPA axis is essential for reproduction, growth, metabolic homeostasis, and responses to stress and they are critical for adapting to changes in the external environment. The regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classical feedback mechanisms in the hypothalamus and the pituitary. The present overview focuses on the neuroendocrine infrastructure of the adaptive response to stress and its effects on the female reproductive system. 

  3. Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators.

    Science.gov (United States)

    Roa, Juan; Tena-Sempere, Manuel

    2014-11-01

    It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    Directory of Open Access Journals (Sweden)

    Tessa K Solomon-Lane

    2013-11-01

    Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  5. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change.

    Science.gov (United States)

    Solomon-Lane, Tessa K; Crespi, Erica J; Grober, Matthew S

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  6. 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.

  7. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 01/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  8. A PHYSIOLOGICALLY BASED COMPUTATIONAL MODEL OF THE BPG AXIS IN FATHEAD MINNOWS: PREDICTING EFFECTS OF ENDOCRINE DISRUPTING CHEMICAL EXPOSURE ON REPRODUCTIVE ENDPOINTS

    Science.gov (United States)

    This presentation describes development and application of a physiologically-based computational model that simulates the brain-pituitary-gonadal (BPG) axis and other endpoints important in reproduction such as concentrations of sex steroid hormones, 17-estradiol, testosterone, a...

  9. Role of neuroendocrine and neuroimmune mechanisms in chronic inflammatory rheumatic diseases--the 10-year update.

    Science.gov (United States)

    Straub, Rainer H; Bijlsma, Johannes W J; Masi, Alfonse; Cutolo, Maurizio

    2013-12-01

    Neuroendocrine immunology in musculoskeletal diseases is an emerging scientific field. It deals with the aspects of efferent neuronal and neurohormonal bearing on the peripheral immune and musculoskeletal systems. This review aims to add new information that appeared since 2001. The following PubMed search sentence was used to find a total of 15,462 references between 2001 and March 2013: "(rheum* OR SLE OR vasculitis) AND (nerve OR hormone OR neurotransmitter OR neuropeptide OR steroid)." In a continuous process, year by year, this search strategy yielded relevant papers that were screened and collected in a database, which build the platform of this review. The main findings are the anti-inflammatory role of androgens, the loss of androgens (androgen drain), the bimodal role of estrogens (support B cells and inhibit macrophages and T cells), increased conversion of androgens to estrogens in inflammation (androgen drain), disturbances of the gonadal axis, inadequate amount of HPA axis hormones relative to inflammation (disproportion principle), biologics partly improve neuroendocrine axes, anti-corticotropin-releasing hormone therapies improve inflammation (antalarmin), bimodal role of the sympathetic nervous system (proinflammatory early, anti-inflammatory late-most probably due to catecholamine-producing local cells), anti-inflammatory role of alpha melanocyte-stimulating hormone, vasoactive intestinal peptide, and the Vagus nerve via α7 nicotinergic receptors. Circadian rhythms of hypothalamic origin are responsible for circadian rhythms of symptoms (neuroimmune link revealed). Important new pain-sensitizing immunological pathways were found in the last decade. The last decade brought much new information that gave birth to the first therapies of chronic inflammatory diseases on the basis of neuroendocrine immune targets. In addition, a new theory linked evolutionary medicine, neuroendocrine regulation of distribution of energy-rich fuels, and volume

  10. The role of the kisspeptin system in regulation of the reproductive endocrine axis and territorial behavior in male side-blotched lizards (Uta stansburiana).

    Science.gov (United States)

    Neuman-Lee, Lorin; Greives, Timothy; Hopkins, Gareth R; French, Susannah S

    2017-03-01

    The neuropeptide kisspeptin and its receptor are essential for activation of the hypothalamic-pituitary-gonadal (HPG) axis and regulating reproduction. While the role of kisspeptin in regulating the HPG axis in mammals has been well established, little is known about the functional ability of kisspeptins to activate the HPG axis and associated behavior in non-mammalian species. Here we experimentally examined the effects of kisspeptin on downstream release of testosterone and associated aggression and display behaviors in the side-blotched lizard (Uta stansburiana). We found that exogenous treatment with kisspeptin resulted in an increase in circulating testosterone levels, castration blocked the kisspeptin-induced increase in testosterone, and testosterone levels in kisspeptin-treated animals were positively related to frequency of aggressive behaviors. This evidence provides a clear link between kisspeptin, testosterone, and aggressive behavior in lizards. Thus, it is likely that kisspeptin plays an important role more broadly in non-mammalian systems in the regulation of reproductive physiology and related behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Quality and Timing of Stressors Differentially Impact on Brain Plasticity and Neuroendocrine-Immune Function in Mice

    Directory of Open Access Journals (Sweden)

    Sara Capoccia

    2013-01-01

    Full Text Available A growing body of evidence suggests that psychological stress is a major risk factor for psychiatric disorders. The basic mechanisms are still under investigation but involve changes in neuroendocrine-immune interactions, ultimately affecting brain plasticity. In this study we characterized central and peripheral effects of different stressors, applied for different time lengths, in adult male C57BL/6J mice. We compared the effects of repeated (7 versus 21 days restraint stress (RS and chronic disruption of social hierarchy (SS on neuroendocrine (corticosterone and immune function (cytokines and splenic apoptosis and on a marker of brain plasticity (brain-derived neurotrophic factor, BDNF . Neuroendocrine activation did not differ between SS and control subjects; by contrast, the RS group showed a strong neuroendocrine response characterized by a specific time-dependent profile. Immune function and hippocampal BDNF levels were inversely related to hypothalamic-pituitary-adrenal axis activation. These data show a fine modulation of the crosstalk between central and peripheral pathways of adaptation and plasticity and suggest that the length of stress exposure is crucial to determine its final outcome on health or disease.

  12. Gonadal Steroid Hormones and the Hypothalamo-Pituitary-Adrenal Axis

    OpenAIRE

    Handa, Robert J.; Weiser, Michael J.

    2013-01-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, pr...

  13. Agonistic reciprocity is associated with reduced male reproductive success within haremic social networks

    Science.gov (United States)

    Solomon-Lane, Tessa K.; Pradhan, Devaleena S.; Willis, Madelyne C.; Grober, Matthew S.

    2015-01-01

    While individual variation in social behaviour is ubiquitous and causes social groups to differ in structure, how these structural differences affect fitness remains largely unknown. We used social network analysis of replicate bluebanded goby (Lythrypnus dalli) harems to identify the reproductive correlates of social network structure. In stable groups, we quantified agonistic behaviour, reproduction and steroid hormones, which can both affect and respond to social/reproductive cues. We identified distinct, optimal social structures associated with different reproductive measures. Male hatching success (HS) was negatively associated with agonistic reciprocity, a network structure that describes whether subordinates ‘reciprocated’ agonism received from dominants. Egg laying was associated with the individual network positions of the male and dominant female. Thus, males face a trade-off between promoting structures that facilitate egg laying versus HS. Whether this reproductive conflict is avoidable remains to be determined. We also identified different social and/or reproductive roles for 11-ketotestosterone, 17β-oestradiol and cortisol, suggesting that specific neuroendocrine mechanisms may underlie connections between network structure and fitness. This is one of the first investigations of the reproductive and neuroendocrine correlates of social behaviour and network structure in replicate, naturalistic social groups and supports network structure as an important target for natural selection. PMID:26156769

  14. Thyroid and male reproduction

    Directory of Open Access Journals (Sweden)

    Anand Kumar

    2014-01-01

    Full Text Available Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH, pituitary luteinizing hormone (LH and follicle stimulating hormone (FSH and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction.

  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 role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    Science.gov (United States)

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Dopamine inhibits reproduction in female zebrafish (Danio rerio) via three pituitary D2 receptor subtypes.

    Science.gov (United States)

    Fontaine, Romain; Affaticati, Pierre; Yamamoto, Kei; Jolly, Cécile; Bureau, Charlotte; Baloche, Sylvie; Gonnet, Françoise; Vernier, Philippe; Dufour, Sylvie; Pasqualini, Catherine

    2013-02-01

    In many teleosts, the stimulatory control of gonadotrope axis by GnRH is opposed by an inhibitory control by dopamine (DA). The functional importance of this inhibitory pathway differs widely from one teleostean species to another. The zebrafish (Danio rerio) is a teleost fish that has become increasingly popular as an experimental vertebrate model. However, the role of DA in the neuroendocrine control of its reproduction has never been studied. Here the authors evaluated in sexually regressed female zebrafish the effects of in vivo treatments with a DA D2 receptor (D2-R) antagonist domperidone, or a GnRH agonist, alone and in combination, on the pituitary level of FSHβ and LHβ transcripts, the gonadosomatic index, and the ovarian histology. Only the double treatment with GnRH agonist and domperidone could induce an increase in the expression of LHβ, in the gonadosomatic index, and a stimulation of ovarian vitellogenesis, indicating that removal of dopaminergic inhibition is required for the stimulatory action of GnRH and reactivation of ovarian function to occur. Using double immunofluorescent staining on pituitary, the authors showed in this species the innervation of LH cells by tyrosine-hydroxylase immunoreactive fibers. Finally, using in situ hybridization and immunofluorescence, the authors showed that the three subtypes of zebrafish DA D2-R (D2a, D2b, and D2c) were expressed in LH-producing cells, suggesting that they all may be involved in mediating this inhibition. These results show for the first time that, in zebrafish, DA has a direct and potent inhibitory action capable of opposing the stimulatory effect of GnRH in the neuroendocrine control of reproduction.

  18. Late neuro endocrinological sequelae of radiation therapy; Effets tardifs de la radiotherapie sur la sphere neuroendocrine

    Energy Technology Data Exchange (ETDEWEB)

    Bieri, S.; Bernier, J. [Ospedale San Giovanni (Switzerland); Sklar, C. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Constine, L. [Rochester Univ., NY (United States)

    1997-12-01

    When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common than has been appreciated in the past. Clinical damage to the pituitary and thyroid glands usually occurs months to years after treatment, and is preceded by a long subclinical phase. Primary brain tumors represent the largest group of malignant solid tumors in children. The survival rates of 50 reported in the literature are achieved at the expense of late occurring effects. Radiation-induced abnormalities are generally dose-dependent. Growth hormone deficiency and premature sexual development can occur at doses as low as 18 Gy in conventional fractionation, and is the most common neuroendocrine problem in children. In patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid stimulation hormone, and adrenocorticotropin (> 50 Gy), hyperprolactinemia can be seen, especially among young women. Most neuroendocrine disturbances that develop as a result of HPA can be treated efficiently, provided that an early detection of these endocrine dysfunctions abnormalities is done. (authors)

  19. Brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    The role of the brain-gut axis has traditionally been investigated in relation to intestinal motility, secretion, and vascularity. More recently, the concept of brain-gut dialogue has extended to the relationship between the nervous system and mucosal immune function. There is compelling evidence for a reciprocal or bi-directional communication between the immune system and the neuroendocrine system. This is mediated, in part, by shared ligands (chemical messengers) and receptors that are common to the immune and nervous systems. Although the concept of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in the context of the systemic immune system, it is likely to have special significance in the gut. The mucosal immune system is anatomically, functionally, and operationally distinct from the systemic immune system and is subject to independent regulatory signals. Furthermore, the intestinal mucosal immune system operates in a local milieu that depends on a dense innervation for its integrity, with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview of evidence for the biologic plausibility of a brain-gut-immune axis is presented and its potential relevance to mucosal inflammatory disorders is discussed.

  20. Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

    Science.gov (United States)

    D'Orsogna, Maria; Chou, Tom; Kim, Lae

    The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

  1. Effects of the insecticide fipronil on reproductive endocrinology in the fathead minnow

    Science.gov (United States)

    Gamma aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic pituitary gonadal (HPG) axis, leading to imp...

  2. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    DEFF Research Database (Denmark)

    Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A

    2015-01-01

    OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...

  3. Cyanohepatotoxins influence on the neuroendocrine and immune systems in fish - a short review.

    Science.gov (United States)

    Sieroslawska, Anna; Rymuszka, Anna

    2009-01-01

    Cyanotoxins are the metabolites of cyanobacteria, belonging to different chemical groups and of diverse mechanisms of toxicity. Generally, they are divided into hepatotoxins, neurotoxins and dermatotoxins/irritant toxins. There is a growing evidence, that besides the above mentioned toxicity, exposure to cyanotoxins may also induce other effects, among others the disruption of neuroendocrine and immune systems. The purpose of that paper is to sum up the current information obtained from the literature and from our own studies about the influence of cyanohepatotoxins on neuroendocrine and immune systems of fish. From the presented data it appears, that microcystins, nodularin and cylindrospermopsin, except for their hepatotoxic activity, are potent to exert such effects as HPI axis activation resulting in physiological and behavioural changes, disturbances in thyroid hormones release/metabolism, as well as impairment of immune responses in fish. However the studies in that area are still incomplete and many questions remain to be answered, especially what consequences for fish population health status it brings.

  4. Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

    Science.gov (United States)

    Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

    2014-02-01

    The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

  5. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    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. Primary Neuroendocrine Tumor of the Breast: Imaging Features

    International Nuclear Information System (INIS)

    Chang, Eun Deok; Kim, Min Kyun; Kim, Jeong Soo; Whang, In Yong

    2013-01-01

    Focal neuroendocrine differentiation can be found in diverse histological types of breast tumors. However, the term, neuroendocrine breast tumor, indicates the diffuse expression of neuroendocrine markers in more than 50% of the tumor cell population. The imaging features of neuroendocrine breast tumor have not been accurately described due to extreme rarity of this tumor type. We present a case of a pathologically confirmed, primary neuroendocrine breast tumor in a 42-year-old woman, with imaging findings difficult to be differentiated from that of invasive ductal carcinoma

  7. Aromatase in the brain: not just for reproduction anymore.

    Science.gov (United States)

    Garcia-Segura, L M

    2008-06-01

    Aromatase, the enzyme that synthesises oestrogens from androgen precursors, is expressed in the brain, where it has been classically associated with the regulation of neuroendocrine events and behaviours linked with reproduction. Recent findings, however, have revealed new unexpected roles for brain aromatase, indicating that the enzyme regulates synaptic activity, synaptic plasticity, neurogenesis and the response of neural tissue to injury, and may contribute to control nonreproductive behaviours, mood and cognition. Therefore, the function of brain aromatase is not restricted to the regulation of reproduction as previously thought.

  8. Neuroendocrine Tumor, diagnostic difficulties

    Directory of Open Access Journals (Sweden)

    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.

  9. Regulation of reproduction by the circadian rhythms.

    Science.gov (United States)

    Zhang, Wen-Xiang; Chen, Si-Yu; Liu, Chang

    2016-12-25

    Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.

  10. Dominance relationships in Syrian hamsters modulate neuroendocrine and behavioral responses to social stress.

    Science.gov (United States)

    Dulka, Brooke N; Koul-Tiwari, Richa; Grizzell, J Alex; Harvey, Marquinta L; Datta, Subimal; Cooper, Matthew A

    2018-06-22

    Stress is a well-known risk factor for psychopathology and rodent models of social defeat have strong face, etiological, construct and predictive validity for these conditions. Syrian hamsters are highly aggressive and territorial, but after an acute social defeat experience they become submissive and no longer defend their home territory, even from a smaller, non-aggressive intruder. This defeat-induced change in social behavior is called conditioned defeat (CD). We have shown that dominant hamsters show increased neural activity in the ventromedial prefrontal cortex (vmPFC) following social defeat stress and exhibit a reduced CD response at social interaction testing compared to subordinates. Although the vmPFC can inhibit the neuroendocrine stress response, it is unknown whether dominants and subordinates differ in stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that, following acute social defeat, dominants exhibit decreased submissive and defensive behavior compared to subordinates but do not differ from subordinates or social status controls (SSCs) in defeat-induced cortisol concentrations. Furthermore, both dominants and SSCs show greater corticotropin-releasing hormone (CRH) mRNA expression in the basolateral/central amygdala compared to subordinates, while there was no effect of social status on CRH mRNA expression in the paraventricular nucleus of the hypothalamus or bed nucleus of the stria terminalis. Overall, status-dependent differences in the CD response do not appear linked to changes in stress-induced cortisol concentrations or CRH gene expression, which is consistent with the view that stress resilience is not a lack of a physiological stress response but the addition of stress coping mechanisms. Lay summary Dominant hamsters show resistance to the behavioral effects of acute social defeat compared to subordinates, but it is unclear whether social status modulates the neuroendocrine stress response

  11. The ecology and evolutionary endocrinology of reproduction in the human female.

    Science.gov (United States)

    Vitzthum, Virginia J

    2009-01-01

    Human reproductive ecology (HRE) is the study of the mechanisms that link variation in reproductive traits with variation in local habitats. Empirical and theoretical contributions from biological anthropology, physiology, and demography have established the foundation necessary for developing a comprehensive understanding, grounded in life history theory (LHT), of temporal, individual, and populational variation in women's reproductive functioning. LHT posits that natural selection leads to the evolution of mechanisms that tend to allocate resources to the competing demands of growth, reproduction, and survival such that fitness is locally maximized. (That is, among alternative allocation patterns exhibited in a population, those having the highest inclusive fitness will become more common over generational time.) Hence, strategic modulation of reproductive effort is potentially adaptive because investment in a new conception may risk one's own survival, future reproductive opportunities, and/or current offspring survival. The hypothalamic-pituitary-ovarian (HPO) axis is the principal neuroendocrine pathway by which the human female modulates reproductive functioning according to the changing conditions in her habitat. Adjustments of reproductive investment in a potential conception are manifested in temporal and individual variation in ovarian cycle length, ovulation, hormone levels, and the probability of conception. Understanding the extent and causes of adaptive and non-adaptive variation in ovarian functioning is fundamental to ascertaining the proximate and remote determinants of human reproductive patterns. In this review I consider what is known and what still needs to be learned of the ecology of women's reproductive biology, beginning with a discussion of the principal explanatory frameworks in HRE and the biometry of ovarian functioning. Turning next to empirical studies, it is evident that marked variation between cycles, women, and populations is the

  12. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.

    Science.gov (United States)

    Pacák, K; Palkovits, M

    2001-08-01

    Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

  13. Prolonged performance-related neuroendocrine activation and perseverative cognition in low- and high-anxious university music students.

    Science.gov (United States)

    Gomez, Patrick; Nielsen, Carole; Studer, Regina K; Hildebrandt, Horst; Klumb, Petra L; Nater, Urs M; Wild, Pascal; Danuser, Brigitta

    2018-05-14

    Music performances are social-evaluative situations that can elicit marked short-term neuroendocrine activation and anxious thoughts especially in musicians suffering from music performance anxiety (MPA). The temporal patterns of neuroendocrine activity and concert-related worry and rumination (perseverative cognition, PC) days before and after a concert in low- and high-anxious musicians are unknown. The first goal of the present study was to investigate the prolonged effects of a solo music performance and the effects of trait MPA on salivary cortisol (sC), alpha-amylase (sAA), and concert-related PC. The second goal was to investigate whether concert-related PC is associated with neuroendocrine activity and mediates the effects of measurement day and trait MPA on neuroendocrine responses. Seventy-two university music students collected saliva samples and reported their PC for seven consecutive days. On the fifth day, they performed solo. Measurement day and trait MPA were tested as main predictors of the diurnal area under the curve with respect to ground (sC AUCg, sAA AUCg), awakening responses, and PC. SC AUCg, sAA AUCg, and concert-related PC were highest on concert day. SC AUCg decreased only partially on post-concert days. SAA AUCg remained elevated on the first post-concert day among students with moderate to very high trait MPA. Throughout the assessment period, trait MPA was associated with smaller sC AUCg and higher concert-related PC. Concert-related PC showed significant positive associations with sC AUCg and sAA AUCg but did not mediate the effects of measurement day and trait MPA on these measures. These findings suggest that solo music performances have prolonged neuroendocrine effects and that trait MPA is an important factor having specific effects on university music students' hypothalamic-pituitary-adrenal axis, autonomic nervous system, and cognitive activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos.

    Science.gov (United States)

    Venerosi, A; Ricceri, L; Tait, S; Calamandrei, G

    2012-12-01

    The complexity of the neuroendocrine level of investigation requires the assessment of behavioral patterns that extend beyond the reproductive functions, which are age- and sex-specific in rodents, described by defined clusters of behavioral items regulated by genetic, hormonal, and epigenetic factors. The study of social behavior in laboratory rodents reveals sex-dimorphic effects of environmental chemicals that may be undetected either by a traditional neurotoxicological approach or referring to the classical definition of endocrine disrupting chemicals. Here we review data on the neurobehavioral effects of developmental exposure to the non-persistent organophosphorus insecticide chlorpyrifos, whose neurotoxic activity at low doses is currently a matter of concern for children's health. In mice exposed to chlorpyrifos in utero and/or in early development social/emotional responses are differently affected in the two sexes in parallel with sex-dependent interference on hypothalamic neuroendocrine pathways regulating social behaviors (vasopressin, oxytocin, and steroid regulated systems). Through the analysis of complex sex-dimorphic behavioral patterns we show that neurotoxic and endocrine disrupting activities of CPF overlap. This widely diffused organophosphorus pesticide might thus be considered as a neuroendocrine disruptor possibly representing a risk factor for sex-biased neurodevelopmental disorders in children. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Richter, Catherine A; Martyniuk, Christopher J; Annis, Mandy L; Brumbaugh, William G; Chasar, Lia C; Denslow, Nancy D; Tillitt, Donald E

    2014-07-01

    Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates. Published by Elsevier Inc.

  16. Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Richter, Catherine A.; Martyniuk, Christopher J.; Annis, Mandy L.; Brumbaugh, William G.; Chasar, Lia C.; Denslow, Nancy D.; Tillitt, Donald E.

    2014-01-01

    Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.

  17. [The relationship between neuroendocrine dysfunction and free-radical oxidation in old age alcoholism].

    Science.gov (United States)

    Vinogradov, D B; Mingazov, A Kh; Izarovskaya, I V; Babin, K A; Sinitsky, A I

    2015-01-01

    to study the relationship between dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and free-radical oxidation in old age alcoholism. Authors examined 46 men and women, aged 60-80 years, with alcoholism. Contents of cortisol, lipid peroxidation products and the level of an oxidatively modified protein were measured. A decrease in blood cortisol content and correlations between its level and activity of free-radical oxidation were identified. The severity of neuroendocrine dysfunction in old patients was sex-related. It has been suggested that the impairment of HPA system activity may be a cause of oxidative stress and development of alcoholism.

  18. Neuroendocrine Carcinomas of the Gastroenteropancreatic System

    DEFF Research Database (Denmark)

    Ilett, Emma Elizabeth; Langer, Seppo W; Olsen, Ingrid Holst

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Conc...

  19. 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....

  20. Nutritional and environmental effects on reproduction in small ruminants.

    Science.gov (United States)

    Martin, G B; Rodger, J; Blache, D

    2004-01-01

    Animals live in environments that are both complex and continually changing, so they have to respond to short- and long-term variations in a wide range of factors, such as photoperiod, nutrition and sociosexual signals. Before they were domesticated, animals developed reproductive strategies that coped with these changes and often took advantage of them. The physiological processes that implement these strategies have been modified to some extent during several millennia of controlled breeding, but most persist. Thus, many genotypes still exhibit profound responses to external inputs, such as the induction of ovulation by sociosexual signals and the doubling of litter size by a change in nutrition. The complexity in these responses is now becoming clearer. For example, with sociosexual signals, we now need to consider the stimulatory effects of males on females, of females on males and of females on females. Similarly, the impact of nutrition has been extended beyond the control of puberty and the production of gametes to include phenomena such as 'fetal programming', with its potentially profound effects on the life-long performance of the animals. Fortunately, our capacity to research these phenomena has been greatly enhanced by technical improvements in hormone assays, molecular and cellular biology, and real-time ultrasound. This has brought us a better understanding of several of the environmental influences on reproduction, including: the cellular processes within ovarian follicles that mediate the effect of nutrition on ovulation rate; the neuroendocrine pathways through which nutritional inputs affect the brain centres that control appetite and reproduction; and the intracerebral pathways through which sociosexual signals (olfactory and non-olfactory) stimulate the reproductive axis. Importantly, we are now beginning to realise that, as well as considering interactions between environmental inputs and genotype, we need to take into account interactions

  1. Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    M. H. Sun

    2004-01-01

    Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.

  2. Pathology of Neuroendocrine Tumours of the Female Genital Tract.

    Science.gov (United States)

    Howitt, Brooke E; Kelly, Paul; McCluggage, W Glenn

    2017-09-01

    Neuroendocrine tumours are uncommon or rare at all sites in the female genital tract. The 2014 World Health Organisation (WHO) Classification of neuroendocrine tumours of the endometrium, cervix, vagina and vulva has been updated with adoption of the terms low-grade neuroendocrine tumour and high-grade neuroendocrine carcinoma. In the endometrium and cervix, high-grade neoplasms are much more prevalent than low-grade and are more common in the cervix than the corpus. In the ovary, low-grade tumours are more common than high-grade carcinomas and the term carcinoid tumour is still used in WHO 2014. The term ovarian small-cell carcinoma of pulmonary type is included in WHO 2014 for a tumour which in other organs is termed high small-cell neuroendocrine carcinoma. Neuroendocrine tumours at various sites within the female genital tract often occur in association with other neoplasms and more uncommonly in pure form.

  3. Relation among HPA and HPG neuroendocrine systems, transmissible risk and neighborhood quality on development of substance use disorder: results of a 10-year prospective study.

    Science.gov (United States)

    Tarter, Ralph E; Kirisci, Levent; Kirillova, Galina; Reynolds, Maureen; Gavaler, Judy; Ridenour, Ty; Horner, Michelle; Clark, Duncan; Vanyukov, Michael

    2013-01-01

    Research has shown involvement of hormones of the hypothalamic pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the regulation of behaviors that contribute to SUD risk and its intergenerational transmission. Neighborhood environment has also been shown to relate to hormones of these two neuroendocrine systems and behaviors associated with SUD liability. Accordingly, it was hypothesized that (1) parental SUD severity and neighborhood quality correlate with activity of the HPG axis (testosterone level) and HPA axis (cortisol stability), and (2) transmissible risk during childhood mediates these hormone variables on development of SUD measured in adulthood. Transmissible risk for SUD measured by the transmissible liability index (TLI; Vanyukov et al., 2009) along with saliva cortisol and plasma testosterone were prospectively measured in boys at ages 10-12 and 16. Neighborhood quality was measured using a composite score encompassing indicators of residential instability and economic disadvantage. SUD was assessed at age 22. Neither hormone variable cross-sectionally correlated with transmissible risk measured at ages 10-12 and 16. However, the TLI at age 10-12 predicted testosterone level and cortisol stability at age 16. Moreover, testosterone level, correlated with cortisol stability at age 16, predicted SUD at age 22. HPA and HPG axes activity do not underlie variation in TLI, however, high transmissible risk in childhood predicts neuroendocrine system activity presaging development of SUD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary.

    Science.gov (United States)

    Whirledge, Shannon; Cidlowski, John A

    2013-12-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

  5. 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.

  6. HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

    Science.gov (United States)

    Jokinen, Jussi; Nordström, Peter

    2008-11-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

  7. Adipokines and the Female Reproductive Tract

    Directory of Open Access Journals (Sweden)

    Maxime Reverchon

    2014-01-01

    Full Text Available It is well known that adipose tissue can influence puberty, sexual maturation, and fertility in different species. Adipose tissue secretes molecules called adipokines which most likely have an endocrine effect on reproductive function. It has been revealed over the last few years that adipokines are functionally implicated at all levels of the reproductive axis including the gonad and hypothalamic-pituitary axis. Many studies have shown the presence and the role of the adipokines and their receptors in the female reproductive tract of different species. These adipokines regulate ovarian steroidogenesis, oocyte maturation, and embryo development. They are also present in the uterus and placenta where they could create a favorable environment for embryonic implantation and play a key role in maternal-fetal metabolism communication and gestation. Reproductive functions are strongly dependent on energy balance, and thereby metabolic abnormalities can lead to the development of some pathophysiologies such as polycystic ovary syndrome (PCOS. Adipokines could be a link between reproduction and energy metabolism and could partly explain some infertility related to obesity or PCOS.

  8. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, Sarah L; Loucks, Tammy L

    2006-12-01

    Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

  10. Cross-talk between estrogen and leptin signaling in the hypothalamus.

    Science.gov (United States)

    Gao, Qian; Horvath, Tamas L

    2008-05-01

    Obesity, characterized by enhanced food intake (hyperphagia) and reduced energy expenditure that results in the accumulation of body fat, is a major risk factor for various diseases, including diabetes, cardiovascular disease, and cancer. In the United States, more than half of adults are overweight, and this number continues to increase. The adipocyte-secreted hormone leptin and its downstream signaling mediators play crucial roles in the regulation of energy balance. Leptin decreases feeding while increasing energy expenditure and permitting energy-intensive neuroendocrine processes, such as reproduction. Thus, leptin also modulates the neuroendocrine reproductive axis. The gonadal steroid hormone estrogen plays a central role in the regulation of reproduction and also contributes to the regulation of energy balance. Estrogen deficiency promotes feeding and weight gain, and estrogen facilitates, and to some extent mimics, some actions of leptin. In this review, we examine the functions of estrogen and leptin in the brain, with a focus on mechanisms by which leptin and estrogen cooperate in the regulation of energy homeostasis.

  11. Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

    Science.gov (United States)

    Daubenbüchel, Anna M. M.; Müller, Hermann L.

    2015-01-01

    Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients. PMID:26239246

  12. Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

    Directory of Open Access Journals (Sweden)

    Anna M. M. Daubenbüchel

    2015-03-01

    Full Text Available Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement, a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92% but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007. Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

  13. (Revised The role of melatonin as a hormone and an antioxidant in the control of fish reproduction

    Directory of Open Access Journals (Sweden)

    Dr. Saumen Kumar Maitra

    2016-05-01

    Full Text Available Reproduction in most fish is seasonal or periodic and the spawning occurs in an appropriate season to ensure maximum survival of the offspring. The sequence of reproductive events in an annual cycle is largely under the control of a species-specific endogenous timing system, which essentially relies on a well-equipped physiological response mechanism to changing environmental cues. The duration of solar light or photoperiod is one of the most predictable environmental signals used by a large number of animals including fish to coordinate their seasonal breeding. In vertebrates, the pineal gland is the major photo-neuroendocrine part of the brain that rhythmically synthesizes and releases melatonin (N-acetyl-5-methoxytryptamine into the circulation in synchronization with the environmental light-dark cycle. Past few decades witnessed an enormous progress in understanding the mechanisms by which melatonin regulates seasonal reproduction in fish and in other vertebrates. Most studies emphasized hormonal actions of melatonin through its high-affinity, pertussis toxin-sensitive G-protein (guanine nucleotide binding protein coupled receptors on the hypothalamus-pituitary-gonad (HPG axis of fish. However, the discovery that melatonin due to its lipophilic nature can easily cross the plasma membrane of all cells and may act as a potent scavenger of free radicals and stimulant of different antioxidants added a new dimension to the idea explaining mechanisms of melatonin actions in the regulation of ovarian functions. The basic concept on the actions of melatonin as an antioxidant emerged from mammalian studies. Recently, however, some new studies clearly suggested that melatonin, apart from playing the role of a hormone, may also be associated with the reduction in oxidative stress to augment ovarian functions during spawning. This review thus aims to bring together the current knowledge on the role of melatonin as a hormone as well as an antioxidant in

  14. Primary neuroendocrine neoplasm of the gallbladder

    OpenAIRE

    Kanakala, Venkatesh; Kasaraneni, Ramesh; Smith, David A; Goulbourne, Ian A

    2009-01-01

    Carcinoid tumours are distinct neuroendocrine tumours with characteristic clinical and histological behavioural properties which arise mainly in the gastrointestinal tract (73.7%) or bronchopulmonary system (25.1%). Neuroendocrine tumours of the gallbladder are rare—to date there have been only 42 cases reported in the literature. This case was an incidental finding which was recognised during routine histopathological examination after laparoscopic cholecystectomy for symptomatic cholelithia...

  15. Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence. The trails study.

    Science.gov (United States)

    Laceulle, Odilia M; Nederhof, Esther; van Aken, Marcel A G; Ormel, Johan

    2017-11-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during adolescence (N=141). HPA-axis functioning (basal cortisol, cortisol awakening response, anticipation of, reaction to and recovery after a stress task) was measured twice, at age 16 and 19. Adversity (i.e., social defeat and loss/illness) since age 16 was measured extensively with the Life Stress Interview at age 19. Adolescents who reported being exposed to social defeat showed increases in basal cortisol (ɳ 2 =0.029) and decreases in reaction to the stress task (ɳ 2 =0.030) from age 16-19, compared to their peers in the loss/illness and no stress group. The current study provides unique longitudinal data on the role of adversity in HPA-axis functioning. Evidence is provided that adversity can affect the body's neuroendocrine response to stress, dependent on the nature of both the HPA-measures and adverse events under study. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 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.)

  17. Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial.

    Science.gov (United States)

    Michopoulos, Vasiliki; Mancini, Fulvia; Loucks, Tammy L; Berga, Sarah L

    2013-06-01

    To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Randomized controlled trial. Clinical research center at an academic medical university. Seventeen women with FHA were randomized either to CBT or observation. CBT versus observation. Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged. In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. NCT01674426. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Neuroendocrine tumors and smoking

    Directory of Open Access Journals (Sweden)

    Tanja Miličević

    2016-12-01

    Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

  19. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    Introduction. Primary neuroendocrine carcinoma (PNEC) of breast ... than 50% neoplastic tumor cells expressing neuroendocrine. (NE) markers .... subtype also concluded that molecular classification helps ... decreased disease free survival.

  20. Leptin and reproduction: a review.

    Science.gov (United States)

    Moschos, Stergios; Chan, Jean L; Mantzoros, Christos S

    2002-03-01

    To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. A MEDLINE computer search was performed to identify relevant articles. Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

  1. 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.

  2. The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction.

    Science.gov (United States)

    Michalakis, Konstantinos G; Segars, James H

    2010-11-01

    To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system. A Medline computer search was performed to identify relevant articles. Research institution. None. Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes. Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles. Published by Elsevier Inc.

  3. 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

    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...... 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....

  4. Insulin-like growth factor-I as a possible hormonal mediator of nutritional regulation of reproduction in cattle.

    Science.gov (United States)

    Zulu, Victor Chisha; Nakao, Toshihiko; Sawamukai, Yutaka

    2002-08-01

    The current review aims to establish insulin-like growth factor-1 (IGF-I) as the factor that signals nutritional status to the reproductive axis, and show that assessment of IGF-I in blood early postpartum during the negative energy balance (NEB) period could be used to predict both nutritional and reproductive status in dairy cattle. The review also explores the effect of nutritional status on circulating IGF-I concentrations and the endocrine role of IGF-I on the reproductive axis. IGF-I plays an important role in gonadotropin-induced folliculogenesis, ovarian steroidogenesis and corpus luteum (CL) function. It also modulates pituitary and hypothalamus function. IGF-I clearly has an endocrine role on the reproductive axis. Severe under nutrition significantly reduces plasma IGF-I concentrations. During the critical period of NEB in high yielding dairy cattle early postpartum, IGF-I concentrations are low in blood and its levels are positively correlated to energy status and reproductive function during this period. Changes in circulating IGF-I immediately postpartum may help predict both nutritional and reproductive status in dairy cattle. IGF-I is therefore one of the long sought factors that signal nutritional status to the reproductive axis.

  5. Neuroendocrine Carcinoma of the Stomach: A Case Study

    Directory of Open Access Journals (Sweden)

    Keisuke Kubota

    2011-01-01

    Full Text Available Gastric neuroendocrine carcinomas are rare and have a poor prognosis, and the diagnostic criteria for this disease have recently changed. We herein report a case of sporadic gastric neuroendocrine carcinoma. A 75-year-old man was referred to our hospital with epigastric pain. Endoscopic examination revealed a localized ulcerative lesion (diameter, 4 cm at the upper stomach. The diagnosis on biopsy was neuroendocrine carcinoma. Total gastrectomy with D2 lymphadenectomy, splenectomy, and cholecystectomy was performed. Pathologically, the tumor infiltrated the subserosal layer, and 6/49 lymph nodes were involved. The tumor was uniform in shape and arranged in a rosette-like structure to form solid nests, with medium-sized, round-to-cuboid-shaped tumor cells and intense mitosis 46/10 HPF. It was positive for synaptophysin and chromogranin A, and the Ki-67 labeling index was 70–80%. The diagnosis of neuroendocrine carcinoma was made according to the WHO 2010 criteria. The patient was followed up for three years without recurrence.

  6. [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.

  7. Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

    Science.gov (United States)

    Xiong, Xiaolu; Zhong, Anyuan; Xu, Huajun

    2014-01-01

    Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG) is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis. Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day) for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH) and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro. MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice. MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

  8. Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

    Directory of Open Access Journals (Sweden)

    Xiaolu Xiong

    Full Text Available Microcystins LR (MC-LR are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis.Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH and luteinizing hormone (LH were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro.MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice.MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

  9. 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

  10. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    International Nuclear Information System (INIS)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J.

    2003-01-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  11. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    Energy Technology Data Exchange (ETDEWEB)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J

    2003-07-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  12. [Serum hormones that regulate the reproductive axis in men with testicular germ cell cancer and its impact on fertility].

    Science.gov (United States)

    Tovar-Rodríguez, José María; Chávez-Zúñiga, Irma; Bañuelos-Ávila, Leticia; Vargas-Hernández, Víctor Manuel; Acosta-Altamirano, Gustavo

    2014-01-01

    Epidemiological studies treat testicular germ cancer as a single disease, the behavior of the two histological types of cancer; seminoma and nonseminoma have differences in reproductive hormone secretion and impair fertility differently. To demonstrate that the serum concentration of pituitary hormones involved in fertility and spermatogenesis in the affected male is different in the two histological types. Were determined by radioimmunoassay or inmunoradiometric assay, luteinizing hormone, follicle stimulating hormone, total testosterone, prolactin, estradiol, human chorionic gonadotropin and alpha fetoprotein in 37 patients with germ cell cancer (15 seminoma and 22 nonseminoma) and 35 controls. We analyzed the semen of patients, and were questioned about paternity before the cancer diagnosis. Age was higher in patients with seminoma cancer, showed decreased luteinizing hormone, follicle stimulating hormone, and testosterone and increased estradiol and prolactin in nonseminoma compared with seminoma. In patients with nonseminoma they had 9 children, 5 were oligozoospermic, 3 azoospermic and 6 normal concentration, 8 did not provide sample, seminoma group they had eight children, only one azoospermic, nine normal concentration, and 5 did not provide sample . The hormonal behavior is different in men with nonseminoma compared with seminoma, so that the negative impact on the reproductive axis and fertility is higher in cases of non-seminoma.

  13. Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

    Science.gov (United States)

    Messina, Antonietta; De Fusco, Carolina; Monda, Vincenzo; Esposito, Maria; Moscatelli, Fiorenzo; Valenzano, Anna; Carotenuto, Marco; Viggiano, Emanuela; Chieffi, Sergio; De Luca, Vincenzo; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2016-01-01

    Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed. PMID:27610076

  14. A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development.

    Science.gov (United States)

    Musumeci, Giuseppe; Castorina, Sergio; Castrogiovanni, Paola; Loreto, Carla; Leonardi, Rosi; Aiello, Flavia Concetta; Magro, Gaetano; Imbesi, Rosa

    2015-01-01

    The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. 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.

  16. Brain serotonin, psychoactive drugs, and effects on reproduction.

    Science.gov (United States)

    Ayala, María Elena

    2009-12-01

    Serotonin, a biogenic amine, is present in significant amounts in many structures of the CNS. It is involved in regulation of a wide variety of physiological functions, such as sensory and motor functions, memory, mood, and secretion of hormones including reproductive hormones. It has also been implicated in the etiology of a range of psychiatric disorders such as anxiety, depression, and eating disorders, along with other conditions such as obesity and migraine. While some drugs that affect serotonin, such as fenfluramine and fluoxetine, have been successfully used in treatment of a range of psychiatric diseases, others, such as the amphetamine analogues MDMA and METH, are potent psychostimulant drugs of abuse. Alterations in serotonergic neurons caused by many of these drugs are well characterized; however, little is known about the reproductive consequences of such alterations. This review evaluates the effects of drugs such as MDMA, pCA, fenfluramine, and fluoxetine on serotonergic transmission in the brain, examines the relationships of these drug effects with the neuroendocrine mechanisms modulating reproductive events such as gonadotropin secretion, ovulation, spermatogenesis, and sexual behavior in animal models, and discusses possible reproductive implications of these drugs in humans.

  17. Social regulation of male reproductive plasticity in an African cichlid fish.

    Science.gov (United States)

    Maruska, Karen P; Fernald, Russell D

    2013-12-01

    Social interactions with the outcome of a position in a dominance hierarchy can have profound effects on reproductive behavior and physiology, requiring animals to integrate environmental information with their internal physiological state; but how is salient information from the animal's dynamic social environment transformed into adaptive behavioral, physiological, and molecular-level changes? The African cichlid fish, Astatotilapia burtoni, is ideally suited to understand socially controlled reproductive plasticity because activity of the male reproductive (brain-pituitary-gonad) axis is tightly linked to social status. Males form hierarchies in which a small percentage of brightly colored dominant individuals have an active reproductive axis, defend territories, and spawn with females, while the remaining males are subordinate, drably colored, do not hold a territory, and have a suppressed reproductive system with minimal opportunities for spawning. These social phenotypes are plastic and quickly reversible, meaning that individual males may switch between dominant and subordinate status multiple times within a lifetime. Here, we review the rapid and remarkable plasticity that occurs along the entire reproductive axis when males rise in social rank, a transition that has important implications for the operational sex ratio of the population. When males rise in rank, transformations occur in the brain, pituitary, circulation, and testes over short time-scales (minutes to days). Changes are evident in overt behavior, as well as modifications at the physiological, cellular, and molecular levels that regulate reproductive capacity. Widespread changes triggered by a switch in rank highlight the significance of external social information in shaping internal physiology and reproductive competence.

  18. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois

    2008-01-01

    Roč. 102, č. 5 (2008), s. 393 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * prostate cancer * neuroendocrine-like cells Subject RIV: BO - Biophysics

  19. Neuroendocrine immune interaction in fish: differential regulation of phagocyte activity by neuroendocrine factors

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Ribeiro, C.M.S.; Chadzinska, M.K.

    2011-01-01

    Coping with physical, chemical and biological disturbances depends on an extensive repertoire of physiological, endocrinological and immunological responses. Fish provide intriguing models to study bi-directional interaction between the neuroendocrine and the immune systems. Macrophages and

  20. Neuroendocrine small cell carcinoma of the uterine cervix.

    Science.gov (United States)

    Reig Castillejo, Anna; Membrive Conejo, Ismael; Foro Arnalot, Palmira; Rodríguez de Dios, Nuria; Algara López, Manuel

    2010-07-01

    Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.

  1. Kisspeptin and energy balance in reproduction.

    Science.gov (United States)

    De Bond, Julie-Ann P; Smith, Jeremy T

    2014-03-01

    Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.

  2. Premenstrual dysphoric disorder: neuroendocrine interferences.

    Science.gov (United States)

    Poiană, Cătălina; Muşat, Mădălina; Carsote, Mara; Chiriţă, Corina

    2009-01-01

    Premenstrual dysphoric disorder (PMDD) consists in severe cognitive and mood changes, more aggressive as seen in premenstrual syndrome (PMS). These two syndromes are situated at the border between gynecology and psychiatry but the link between the two domains remains the neuroendocrine underlying mechanisms. In present, there are some molecular systems certainly proved as being involved, like estrogens. The hormonal pattern consists not in different levels of the hormones but different response to normal hormonal levels. The cyclical biochemical triggers are related to neurotransmitters as serotonin, endorphin and gamma-amino butyric acid (GABA). The heritability of the syndrome is sustained by genetic polymorphism in ESR1 gene. Thus, the PMDD is the result of multiple disturbances regarding neuroendocrine systems.

  3. Chapter 22: Female Reproductive Toxicology

    Science.gov (United States)

    The female reproductive system provides multiple targets for environmental toxicants with the hypothalamic-pituitary-ovarian axis. Moreover, the functional impact of a chemical can differ, depending on the species involved and the parameters of exposure. While cross-species compa...

  4. Alternations in neuroendocrine and endocrine regulation of reproduction in male goldfish (Carassius auratus) following an acute and chronic exposure to vinclozolin, in vivo.

    Science.gov (United States)

    Golshan, Mahdi; Hatef, Azadeh; Zare, Ava; Socha, Magdalena; Milla, Sylvain; Gosiewski, Grzegorz; Fontaine, Pascal; Sokołowska-Mikołajczyk, Mirosława; Habibi, Hamid R; Alavi, Sayyed Mohammad Hadi

    2014-10-01

    The fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100, 400 and 800 μg/L VZ and 5 μg/L 17β-estradiol (E2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 μg/L VZ, while it was increased in goldfish exposed to 100 μg/L VZ after 30 days of exposure. Circulating E2 level was unchanged in VZ treated goldfish, however the E2/11-KT ratio was increased in a concentration-related manner. In E2 treated goldfish, circulatory 11-KT and E2 levels were decreased and increased, respectively, which resulted in an increase in the E2/11-KT ratio. Exposure to VZ at 100 μg/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3β-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    Pavel M.E., Baum U., Hahn E.G., Hensen J. Doxorubucin and streptozocin after failed biotherapy of Neuroendocrine tumors. Int J. Gastrointest Cancer 2005; 35 179-185. 33. Yao J.C., Phan A., Hoff P.M., et al. Targeting vas- cular endothelial growth factor in advanced carci- noid tumors: a random assignment phase II study.

  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. Aloysia triphylla in the zebrafish food: effects on physiology, behavior, and growth performance.

    Science.gov (United States)

    Zago, Daniane C; Santos, Alessandro C; Lanes, Carlos F C; Almeida, Daniela V; Koakoski, Gessi; de Abreu, Murilo S; Zeppenfeld, Carla C; Heinzmann, Berta M; Marins, Luis F; Baldisserotto, Bernardo; Barcellos, Leonardo J G; Cunha, Mauro A

    2018-04-01

    Dietary supplements are commonly used by animals and humans and play key roles in diverse systems, such as the immune and reproductive systems, and in metabolism. Essential oils (EOs), which are natural substances, have potential for use in food supplementation; however, their effects on organisms remain to be elucidated. Here, we examine the effects of dietary Aloysia triphylla EO supplementation on zebrafish behavior, metabolism, stress response, and growth performance. We show that fish fed diets containing A. triphylla EO presented an anxiolytic response, with reduced exploratory activity and oxygen consumption; no changes were observed in neuroendocrine stress axis functioning and growth was not impaired. Taken together, these results suggest that the A. triphylla EO supplementation is a strong candidate for use in feed, since it ensures fish welfare (anxiolytic behavior) with decreased oxygen consumption. This makes it suitable for use in high-density production systems without causing damage to the neuroendocrine stress axis and without growth performance being impaired.

  8. Brain angiotensin-(1-7)/Mas axis: A new target to reduce the cardiovascular risk to emotional stress.

    Science.gov (United States)

    Fontes, Marco Antônio Peliky; Martins Lima, Augusto; Santos, Robson Augusto Souza dos

    2016-04-01

    Emotional stress is now considered a risk factor for several diseases including cardiac arrhythmias and hypertension. It is well known that the activation of neuroendocrine and autonomic mechanisms features the response to emotional stress. However, its link to cardiovascular diseases and the regulatory mechanisms involved remain to be further comprehended. The renin-angiotensin system (RAS) plays an important role in homeostasis on all body systems. Specifically in the brain, the RAS regulates a number of physiological aspects. Recent data indicate that the activation of angiotensin-converting enzyme/angiotensin II/AT1 receptor axis facilitates the emotional stress responses. On the other hand, growing evidence indicates that its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/(Ang)iotensin-(1-7)/Mas axis, reduces anxiety and attenuates the physiological responses to emotional stress. The present review focuses on angiotensin-(1-7)/Mas axis as a promising target to attenuate the physiological response to emotional stress reducing the risk of cardiovascular diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    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

  10. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    OpenAIRE

    Whirledge, Shannon; Cidlowski, John A.

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that oth...

  11. 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...... these PET tracers further....

  12. Radiology of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Hako, R.; Hakova, H.; Gulova, I.

    2011-01-01

    Neuroendocrine tumors arise in the bronchopulmonary or gastrointestinal tract, but they can arise in almost any organ. The tumors have varied malignant potential depending on the site of their origin. Metastases may be present at the time of diagnosis, which often occurs at a late stage of the disease. Most NETs have nonspecific imaging characteristics. Imaging plays a pivotal role in the localization and staging of neuroendocrine tumors and in monitoring the treatment response. Imaging should involve multi-phase computed tomography, contrast material-enhanced magnetic resonance imaging, contrast-enhanced ultrasonography and other one. Hepatic metastatic disease in particular lends itself to a wide range of interventional treatment options. Transcatheter arterial embolization may be used alone or in combination with chemo embolization. Ablative techniques, hepatic cryotherapy and percutaneous ethanol injection may then be undertaken. A multidisciplinary approach to treatment and follow-up is important. (author)

  13. Reproductive toxicity: Male and female reproductive systems as targets for chemical injury

    Energy Technology Data Exchange (ETDEWEB)

    Mattison, D.R.; Plowchalk, D.R.; Meadows, M.J.; Al-Juburi, A.Z.; Gandy, J.; Malek, A. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-03-01

    On the basis of current knowledge of reproductive biology and toxicology, it is apparent that chemicals affecting reproduction may elicit their effects at a number of sites in both the male and the female reproductive system. This multiplicity of targets is attributable to the dynamic nature of the reproductive system, in which the hypothalamic-pituitary-gonadal axis is controlled by precise positive and negative feedback mechanisms among its components. Interference by a xenobiotic at any level in either the male or the female reproductive system may ultimately impair hypothalamic or pituitary function. Normal gonadal processes such as spermatogenesis or oogenesis, ejaculation or ovulation, hormone production by Leydig or granulosa cells, and the structure or function of the accessory reproductive structures (e.g., epididymis, fallopian tube) also appear vulnerable to xenobiotics. The reproductive system is a complex one that requires local and circulating hormones for control. This brief review illustrates a system for characterizing the mechanism of action of reproductive toxicants, as well as for defining the sites available for disruption of reproduction. Unfortunately, at present, data addressing the actual vulnerability of reproduction are sorely lacking. However, when experiments have been conducted and combined with epidemiologic data or clinical observation, it has been possible to demonstrate impairment of reproductive processes by xenobiotics. The role of environmental exposure to xenobiotics in the increase in infertility that has been observed remains to be defined. 87 references.

  14. Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

    Science.gov (United States)

    Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

    2015-06-01

    A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

  15. Food, stress, and reproduction: short-term fasting alters endocrine physiology and reproductive behavior in the zebra finch.

    Science.gov (United States)

    Lynn, Sharon E; Stamplis, Teresa B; Barrington, William T; Weida, Nicholas; Hudak, Casey A

    2010-07-01

    Stress is thought to be a potent suppressor of reproduction. However, the vast majority of studies focus on the relationship between chronic stress and reproductive suppression, despite the fact that chronic stress is rare in the wild. We investigated the role of fasting in altering acute stress physiology, reproductive physiology, and reproductive behavior of male zebra finches (Taeniopygia guttata) with several goals in mind. First, we wanted to determine if acute fasting could stimulate an increase in plasma corticosterone and a decrease in corticosteroid binding globulin (CBG) and testosterone. We then investigated whether fasting could alter expression of undirected song and courtship behavior. After subjecting males to fasting periods ranging from 1 to 10h, we collected plasma to measure corticosterone, CBG, and testosterone. We found that plasma corticosterone was elevated, and testosterone was decreased after 4, 6, and 10h of fasting periods compared with samples collected from the same males during nonfasted (control) periods. CBG was lower than control levels only after 10h of fasting. We also found that, coincident with these endocrine changes, males sang less and courted females less vigorously following short-term fasting relative to control conditions. Our data demonstrate that acute fasting resulted in rapid changes in endocrine physiology consistent with hypothalamo-pituitary-adrenal axis activation and hypothalamo-pituitary-gonadal axis deactivation. Fasting also inhibited reproductive behavior. We suggest that zebra finches exhibit physiological and behavioral flexibility that makes them an excellent model system for studying interactions of acute stress and reproduction. Copyright 2010 Elsevier Inc. All rights reserved.

  16. The gonadotropin-inhibitory hormone (Lpxrfa) system's regulation of reproduction in the brain-pituitary axis of the zebrafish (Danio rerio).

    Science.gov (United States)

    Spicer, Olivia Smith; Zmora, Nilli; Wong, Ten-Tsao; Golan, Matan; Levavi-Sivan, Berta; Gothilf, Yoav; Zohar, Yonathan

    2017-05-01

    Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (LPXRFamide (Lpxrfa) peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary. In the preoptic area, Lpxrfa fibers interact with gonadotropin-releasing hormone 3 (Gnrh3) soma. In pituitary explants, zebrafish peptide Lpxrfa-3 downregulated luteinizing hormone beta subunit and common alpha subunit expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices, offering another pathway for Lpxrfa to exert its effects on reproduction. Receptor activation studies, in a heterologous cell-based system, revealed that all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kisspeptin-2 (Kiss2) activation of Kisspeptin receptor-1a (Kiss1ra). The fact that kiss1ra-expressing neurons in the preoptic area are innervated by Lpxrfa-ir fibers suggests an additional pathway for Lpxrfa action. Therefore, our results suggest that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish that interacts with Gnrh3 neurons in the brain and with gonadotropes in the pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Radiosensitivity related to neuroendocrine and endodermal differentation in lung carcinoma lines

    International Nuclear Information System (INIS)

    Duchesne, G.; Casoni, A.; Pera, M.

    1988-01-01

    A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentation. An index of the degree of neuroendocrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurofilaments and an embryonic endodermal cell marker, which allowed identification of three groups showing high, intermediate or low neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endodermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. 30 refs.; 3 figs.; 3 tabs

  18. Bioethics and Biopolitics: Presents and Futures of Reproduction.

    Science.gov (United States)

    Camporesi, Silvia

    2017-06-01

    This Bioethics and Biopolitics: Presents and Futures of Reproduction symposium draws together a series of articles that were each submitted independently by their authors to the JBI and which explore the biopower axis in the externalization of reproduction in four contexts: artificial gestation (ectogenesis), PGD for sex selection, women's (reproductive) rights, and testicular cryopreservation (TCCP). While one contribution explores a "future" of reproduction, the other three explore a "present," or better, explore different "presents." What may counts as "present," and what may count as "future," has dramatically different connotations depending on the geographical declination of the tense.

  19. Tumors of the endocrine/neuroendocrine system: an overview.

    Science.gov (United States)

    Erlandson, R A; Nesland, J M

    1994-01-01

    For the sake of discussion, the markedly diversified tumors of the endocrine/neuroendocrine system are classified as those originating in classic epithelial endocrine organs (eg, adrenal cortical adenomas), from the diffuse endocrine cells (eg, jejunal carcinoid tumors), or from clusters of these cells (eg, islet cell tumors); and those arising from neurosecretory neurons (eg, neuroblastoma) or paraganglia (eg, carotid body tumor). Although traditional transmission electron microscopy is useful for identifying neurosecretory or endosecretory granules as such, with few exceptions (eg, insulin-containing granules with a complex paracrystalline core) it is not possible to ascribe a granule type (size, shape, or ultrastructure) to a distinct nosologic entity or secretory product because of their overlapping fine structures in different cell types. Immunoelectron microscopy methods utilizing colloidal gold-labeled secondary antibodies can be used to localize virtually any antigen (peptide or neuroamine) to a specific neurosecretory or endosecretory granule or other cell structure. General endocrine/neuroendocrine cell markers such as neuron-specific enolase, the chromogranins, and synaptophysin are useful in identifying neuroendocrine differentiation in a neoplasm using routine immunohistochemical procedures. The current relevance of the APUD concept of Pearse as well as the biologic importance of endocrine/neuroendocrine secretory products such as bombesin and insulinlike growth factors also are discussed.

  20. Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system.

    Science.gov (United States)

    Slominski, Andrzej T; Zmijewski, Michal A; Skobowiat, Cezary; Zbytek, Blazej; Slominski, Radomir M; Steketee, Jeffery D

    2012-01-01

    Skin, the body's largest organ, is strategically located at the interface with the external environment where it detects, integrates, and responds to a diverse range of stressors including solar radiation. It has already been established that the skin is an important peripheral neuro-endocrine-immune organ that is tightly networked to central regulatory systems. These capabilities contribute to the maintenance of peripheral homeostasis. Specifically, epidermal and dermal cells produce and respond to classical stress neurotransmitters, neuropeptides, and hormones. Such production is stimulated by ultraviolet radiation (UVR), biological factors (infectious and noninfectious), and other physical and chemical agents. Examples of local biologically active products are cytokines, biogenic amines (catecholamines, histamine, serotonin, and N-acetyl-serotonin), melatonin, acetylocholine, neuropeptides including pituitary (proopiomelanocortin-derived ACTH, beta-endorphin or MSH peptides, thyroid-stimulating hormone) and hypothalamic (corticotropin-releasing factor and related urocortins, thyroid-releasing hormone) hormones as well as enkephalins and dynorphins, thyroid hormones, steroids (glucocorticoids, mineralocorticoids, sex hormones, 7-delta steroids), secosteroids, opioids, and endocannabinoids. The production of these molecules is hierarchical, organized along the algorithms of classical neuroendocrine axes such as hypothalamic-pituitary-adrenal axis (HPA), hypothalamic-thyroid axis (HPT), serotoninergic, melatoninergic, catecholaminergic, cholinergic, steroid/secosteroidogenic, opioid, and endocannbinoid systems. Dysregulation of these axes or of communication between them may lead to skin and/ or systemic diseases. These local neuroendocrine networks are also addressed at restricting maximally the effect of noxious environmental agents to preserve local and consequently global homeostasis. Moreover, the skin-derived factors/systems can also activate cutaneous nerve

  1. Immunohistochemical evidence for an endocrine/paracrine role for ghrelin in the reproductive tissues of sheep

    Directory of Open Access Journals (Sweden)

    Brown Yvonne A

    2005-10-01

    Full Text Available Abstract Background The gut hormone, ghrelin, is involved in the neuroendocrine and metabolic responses to hunger. In monogastric species, circulating ghrelin levels show clear meal-related and body weight-related changes. The pattern of secretion and its role in ruminant species is less clear. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a to alter food intake, fat utilization, and cellular proliferation. There is also evidence that ghrelin is involved in reproductive function. In the present study we used immunohistochemistry to investigate the presence of ghrelin and GHSR-1a in sheep reproductive tissues. In addition, we examined whether ghrelin and GHSR-1a protein expression is developmentally regulated in the adult and fetal ovine testis, and whether there is an association with markers of cellular proliferation, i.e. stem cell factor (SCF and proliferating cell nuclear antigen (PCNA. Methods Antibodies raised against ghrelin and its functional receptor, GHSR-type 1a, were used in standard immunohistochemical protocols on various reproductive tissues collected from adult and fetal sheep. GHSR-1a mRNA presence was also confirmed by in situ hybridisation. SCF and PCNA immunoexpression was investigated in fetal testicular samples. Adult and fetal testicular immunostaining for ghrelin, GHSR-1a, SCF and PCNA was analysed using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference. Results In adult sheep tissue, ghrelin and GHSR-1a immunostaining was detected in the stomach (abomasum, anterior pituitary gland, testis, ovary, and hypothalamic and hindbrain regions of the brain. In the adult testis, there was a significant effect of season (photoperiod on the level of immunostaining for ghrelin (p Conclusion Evidence is presented for the presence of ghrelin and its receptor in various reproductive

  2. Colorectal neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

    Science.gov (United States)

    Starzyńska, Teresa; Londzin-Olesik, Magdalena; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Blicharz-Dorniak, Jolanta; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Deptała, Andrzej; 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; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Lipiński, Michał; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Remiszewski, Piotr; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; 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

    Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer-tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358-368.

  3. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2017-09-26

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  4. 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...

  5. Multiscale mathematical modeling of the hypothalamo-pituitary-gonadal axis.

    Science.gov (United States)

    Clément, Frédérique

    2016-07-01

    Although the fields of systems and integrative biology are in full expansion, few teams are involved worldwide into the study of reproductive function from the mathematical modeling viewpoint. This may be due to the fact that the reproductive function is not compulsory for individual organism survival, even if it is for species survival. Alternatively, the complexity of reproductive physiology may be discouraging. Indeed, the hypothalamo-pituitary-gonadal (HPG) axis involves not only several organs and tissues but also intricate time (from the neuronal millisecond timescale to circannual rhythmicity) and space (from molecules to organs) scales. Yet, mathematical modeling, and especially multiscale modeling, can renew our approaches of the molecular, cellular, and physiological processes underlying the control of reproductive functions. In turn, the remarkable dynamic features exhibited by the HPG axis raise intriguing and challenging questions to modelers and applied mathematicians. In this article, we draw a panoramic review of some mathematical models designed in the framework of the female HPG, with a special focus on the gonadal and central control of follicular development. On the gonadal side, the modeling of follicular development calls to the generic formalism of structured cell populations, that allows one to make mechanistic links between the control of cell fate (proliferation, differentiation, or apoptosis) and that of the follicle fate (ovulation or degeneration) or to investigate how the functional interactions between the oocyte and its surrounding cells shape the follicle morphogenesis. On the central, mainly hypothalamic side, models based on dynamical systems with multiple timescales allow one to represent within a single framework both the pulsatile and surge patterns of the neurohormone GnRH. Beyond their interest in basic research investigations, mathematical models can also be at the source of useful tools to study the encoding and decoding of

  6. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. EFFECTS OF CADMIUM ON THE REPRODUCTIVE AXIS OF JAPANESE MEDAKA

    Science.gov (United States)

    Cadmium (Cd) is a ubquitous element and a significant inorganic pollutant that has previously been found to bioaccumulate in reproductive organs of fish and disrupt important endocrine processes, especially those involved in synthesis, release and metabolism of hormones. Clearly,...

  8. Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.

    Science.gov (United States)

    Cowell, Whitney J; Wright, Rosalind J

    2017-12-01

    Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos, and traffic-related air pollution). We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits, and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.

  9. The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer

    Science.gov (United States)

    2009-01-01

    AD_________________ Award Number: W81XWH-07-1-0061 TITLE: The Function of PTP1B in Neuroendocrine...The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer 5b. GRANT NUMBER W81XWH-07-1-0061 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8

  10. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumours

    DEFF Research Database (Denmark)

    Partelli, Stefano; Bartsch, Detlef K.; Capdevila, Jaume

    2017-01-01

    The small intestine and pancreas are among the most frequent abdominal sites of origin of neuroendocrine tumours. Distinctive features of these forms are represented by the relatively low incidence and the wide heterogeneity in biological behaviour. In this light, it is difficult to standardize...... indications for surgery and the most appropriate approach. It would be helpful for surgeons managing patients with these tumours to have guidelines for surgical treatment of small intestinal neuroendocrine tumours and pancreatic neuroendocrine tumours. The proposed guidelines represent a consensus...

  11. Gastroenteropancreatic neuroendocrine tumors (GEP-NETS)

    International Nuclear Information System (INIS)

    Vargas Martinez, Cristian Camilo; Castano Llano, Rodrigo

    2010-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are rare neoplasms which can occur anywhere in the gastrointestinal tract. Their particular characteristics include uptake of silver salts, neuroendocrine cell marker expression and hormonal secretory granules. Depending on their size, anatomical location and upon whether or not metastasis has occurred, these tumors can show different clinical patterns and have different prognoses. Early diagnosis is essential for treating these lesions and improving the patients' prognoses, but it requires a high degree of suspicion and confirmation by special testing. Surgical treatment is the first choice, but other medical therapy can be helpful for patients who have unresectable disease. This review presents the most relevant aspects of classification, morphology, methods of locating tumors, diagnosis and treatment of GEP-NETS. It presents only the Colombian experience in the epidemiology and management of these tumors.

  12. 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.

  13. Adaptive Response in Female Modeling of the Hypothalamic-pituitary-gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  14. Permanent and plastic epigenesis in neuroendocrine systems.

    Science.gov (United States)

    Auger, Catherine J; Auger, Anthony P

    2013-08-01

    The emerging area of neuroepigenetics has been linked to numerous mental health illnesses. Importantly, a large portion of what we know about early gene×environment interactions comes from examining epigenetic modifications of neuroendocrine systems. This review will highlight how neuroepigenetic mechanisms during brain development program lasting differences in neuroendocrine systems and how other neuroepigenetic processes remain plastic, even within the adult brain. As epigenetic mechanisms can either be stable or plastic, elucidating the mechanisms involved in reversing these processes could aid in understanding how to reverse pathological epigenetic programming. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

    Science.gov (United States)

    Sandhu, Kiran V; Sherwin, Eoin; Schellekens, Harriët; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-01-01

    The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations.

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    Nicola Fusco

    Full Text Available Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.

  17. Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling

    Science.gov (United States)

    O’Neill, Casey E.; Newsom, Ryan J.; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C.; Spencer, Robert L.; Campeau, Serge; Bachtell, Ryan K.

    2016-01-01

    Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3 g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24 h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24 h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence

  18. Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling.

    Science.gov (United States)

    O'Neill, Casey E; Newsom, Ryan J; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C; Spencer, Robert L; Campeau, Serge; Bachtell, Ryan K

    2016-05-01

    Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased

  19. Neuroendocrine Consequences of Anorexia Nervosa in Adolescents

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Anorexia nervosa (AN) is a condition of severe undernutrition characterized by alterations in multiple neuroendocrine axes and peptides that signal or regulate energy intake. These alterations include a state of hypogonadotropic hypogonadism, a nutritionally acquired resistance to growth hormone (GH) with low IGF-1 levels, relative hypercortisolemia, low total T3 despite normal TSH, low levels of leptin and insulin, and elevated levels of ghrelin, peptide YY (PYY) and possibly adiponectin. Although many of these changes are adaptive to low weight, they can impact bone metabolism, body composition, reproductive function and statural growth. Low bone mass is characteristic of AN in both adolescent boys and girls. In girls, sites of trabecular bone are more likely to be affected than sites of cortical bone, whereas in boys with AN, sites of cortical bone are more commonly affected. Bone microarchitecture is also affected in adolescent girls with AN, with a decrease in trabecular thickness and bone trabecular volume, and an increase in trabecular separation. Important predictors of low bone density include nutritional factors, body composition, hypogonadism, low IGF-1, elevated cortisol and PYY levels, with possible contributions of low insulin. Weight gain is associated with a stabilization of bone density, although residual deficits persist in the short term, and in some cases, long term. PMID:19955768

  20. WHO Grade 2 Neuroendocrine Tumor in a 15-Year-Old Male: A Case Report and Literature Review

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    Eric Johannesen

    2014-01-01

    Full Text Available Neuroendocrine tumors, distinguished from adenocarcinomas by their neuroendocrine differentiation, are the most common pediatric epithelial malignancy that most often occurs in the appendix. In 2010, the WHO classified neuroendocrine neoplasms into three grades based on morphology, mitotic count, and Ki67 proliferation index. A 15-year-old male with a history of anemia and failure to thrive was diagnosed with a well-differentiated neuroendocrine tumor in the jejunum that invaded into the subserosal soft tissue and metastasized to four lymph nodes. Pediatric neuroendocrine tumors frequently arise within hereditary tumor syndromes with pancreatic neuroendocrine tumors being the most common. Several studies also indicate an elevated risk of small intestinal neuroendocrine tumors in which children born to a parent with a history of neuroendocrine tumors in the small intestine have a significant increased risk of developing one.

  1. Induction of Gonadotropins for Reproductive Control

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    Elza Ibrahim Auerkari

    2015-10-01

    Full Text Available Much of the recent research on gonadotropin – related control processes of reproduction and reproductive maturation has concentrated on the neuronal and molecular biology of gonadotropin release. The reproductive development of healthy mammals requires appropriate fetal develompment and migration of the neural network controlling and including the gonadotropin releasing hormone (GnRH – producing neurons that are needed to regulate GnRH and luteinizing hormone (LH release. GnRH is also necessary for the development of the gonadotropin – producing pituitary gland. The fetal gonads respon to GnRH – induced LH production by producing the gonadal steroids required for further reproductive differentiation. Pubertal maturation is characterised by increases in LH levels, representing the corresponding pulsatile release of GnRH. This GnRH pulse generator appears to be an intrinsic property of the arcuate nucleus at the medial basal hypothalamus. The generator activity can be mediated by the neurotransmitter aspartate which activates neurons of the hypothalamus, inducing acuate releases of GnRH and hence initiates puberty. A major factor in human reproductive maturation is the decrease in the age of puberty, caused by improvement of nutritional conditions due to the socio – economic development. This implies that the pubertal activation of GnRH secretion depends on metabolic conditions. Of the substances that mediate the metabolic condition to the neuronal network regulating GnRH secretion, the role of the neuropeptide Y (NPY appears instrumental : for healthy mammals less food means more NPY, and accumulated NPY makes food to become sex. NPY does this by regulating the appropriate hypothalamic functions including the neuroendocrine control of gonadotropin release.

  2. Colonic neuroendocrine carcinoma in a child

    International Nuclear Information System (INIS)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes; Sathiapalan, Rajeev; Kofide, Amani; Tulbah, Asthma Mahmoud Mohamed; Al-Mehaidib, Ali

    2005-01-01

    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.)

  3. Model-based therapeutic correction of hypothalamic-pituitary-adrenal axis dysfunction.

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    Amos Ben-Zvi

    2009-01-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS. At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning.

  4. Chronic diarrhea as presenting symptom for a metastasic neuroendocrine tumor

    International Nuclear Information System (INIS)

    Hani A, Albis Cecilia; Garcia A, Jairo Alberto

    2007-01-01

    We describe the clinical case of a 74 years old female patient presenting with a watery diarrhea syndrome, having severe hypokalaemia and liver metastases. In her necropsy a pancreatic neuroendocrine tumor was found. We present a literature review about pancreas neuroendocrine tumours, focusing in the VIPoma, which may correspond with the clinical features of this particular patient

  5. 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.

  6. Peptide receptor radionuclide therapy of neuroendocrine tumours

    International Nuclear Information System (INIS)

    Bodei, L.; Giammarile, F.

    2009-01-01

    Neuroendocrine tumours are considered relatively rare tumours that have the characteristic property of secreting bioactive substances, such as amines and hormones. They constitute a heterogeneous group, characterized by good prognosis, but important disparities of the evolutionary potential. In the aggressive forms, the therapeutic strategies are limited. The metabolic or internal radiotherapy, using radiolabelled peptides, which can act at the same time on the primary tumour and its metastases, constitutes a tempting therapeutic alternative, currently in evolution. The prospects are related to the development of new radiopharmaceuticals, with the use of other peptide analogues whose applications will overflow the framework of the neuro-endocrine tumours. (authors)

  7. Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

    Science.gov (United States)

    Ramalingam, Sundhar; Eisenberg, Adva; Foo, Wen Chi; Freedman, Jennifer; Armstrong, Andrew J; Moss, Larry G; Harrison, Michael R

    2016-12-01

    Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome. © 2016 The Japanese Urological Association.

  8. Large Cell Neuroendocrine Cancer (LCNEC of uterine cervix

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    Gehanath Baral

    2009-01-01

    Full Text Available A rare type of cervical cancer was encountered as a neuroendocrine cancer of cervix. Clinically, the patient presented with bleeding per vagina. She refused biopsy in her first visit and did not come for follow up. However, after few months she came and since there was a polypoid growth from cervix, she was advised to undergo hysterectomy. Histopathologically, it was diagnosed as large cell type of neuroendocrine cancer. Multimodality systemic treatment was offered as per literature. Ibrahim Med. Coll. J. 2009; 3(1: 36-38

  9. RFRP neurons - the doorway to understanding seasonal reproduction in mammals

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    Jo Beldring Henningsen

    2016-05-01

    Full Text Available Seasonal control of reproduction is critical for the perpetuation of species living in temperate zones that display major changes in climatic environment and availability of food resources. In mammals, seasonal cues are mainly provided by the annual change in the 24h light/dark ratio (i.e. photoperiod, which is translated into the nocturnal production of the pineal hormone melatonin. The annual rhythm in this melatonin signal acts as a synchronizer ensuring that breeding occurs when environmental conditions favor survival of the offspring. Although specific mechanisms might vary among seasonal species, the hypothalamic RF (Arg-Phe amide-related peptides (RFRP-1 and -3 are believed to play a critical role in the central control of seasonal reproduction and in all seasonal species investigated, the RFRP system is persistently inhibited in short photoperiod. Central chronic administration of RFRP-3 in short day-adapted male Syrian hamsters fully reactivates the reproductive axis despite photoinhibitory conditions, which highlights the importance of the seasonal changes in RFRP expression for proper regulation of the reproductive axis. The acute effects of RFRP peptides, however, depend on species, photoperiod and recent studies point towards a different role of RFRP in regulating female reproductive activity. In this review we summarize the recent advances made to understand the role and underlying mechanisms of RFRP in the seasonal control of reproduction, primarily focusing on mammalian species.

  10. Neuroendocrine Regulation of Maternal Behavior

    Science.gov (United States)

    Bridges, Robert S.

    2015-01-01

    The expression of maternal behavior in mammals is regulated by the developmental and experiential events over a female’s lifetime. In this review the relationships between the endocrine and neural systems that play key roles in these developmental and experiential that affect both the establishment and maintenance of maternal care are presented. The involvement of the hormones estrogen, progesterone, and lactogens are discussed in the context of ligand, receptor, and gene activity in rodents and to a lesser extent in higher mammals. The roles of neuroendocrine factors, including oxytocin, vasopressin, classical neurotransmitters, and other neural gene products that regulate aspects of maternal care are set forth, and the interactions of hormones with central nervous system mediators of maternal behavior are discussed. The impact of prior developmental factors, including epigenetic events, and maternal experience on subsequent maternal care are assessed over the course of the female’s lifespan. It is proposed that common neuroendocrine mechanisms underlie the regulation of maternal care in mammals. PMID:25500107

  11. [Effect of Electroacupuncture on Hypothalamus-Pituitary-Ovary (HPO) Axis in Rats with Peri-menopausal Depression].

    Science.gov (United States)

    Jiang, Xi-Rong; Ren, Lu; Li, Chun-Ri

    2017-02-25

    To observe the effect of electroacupuncture (EA) on the hormones derived from the hypothalamus-pituitary-ovary (HPO) axis, so as to explore the neuroendocrine mechanism induced by EA on rats with perimenopausal depression disorder. Sixty female sprague-dawley rats were randomly divided into blank control group, model group, sham-operation (sham) group, clomipramine group, and electroacupuncture (EA) group, with 12 rats in each group. Perimenopausal depression model was established by bilateral ovariectomy combined with chronic unpredictable stimulation.The EA group received continuous treatment at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) once a day for 28 days. Estrous cycle and sucrose preference test were monitored, and serum estradiol (E 2 ), luteinizing hormone (LH), gonadotropin releasing hormone (GnRH), and β-endorphin (β-EP) were detected by ELISA. Compared to the blank control group, sugar water consumpution rates decreased in the model group and sham group ( P Electroacupuncture can relieve the symptoms of rat with perimenopausal depression by regulating the hormone secretion in HPO axis.

  12. [Neuroendocrine carcinoma of the digestive tract: a literature review].

    Science.gov (United States)

    Jacob, J; Chargari, C; Helissey, C; Ferrand, F-R; Ceccaldi, B; Le Moulec, S; Bauduceau, O; Fayolle, M; Védrine, L

    2013-11-01

    Neuroendocrine carcinoma is a rare and agressive malignant tumor, mainly developing at the expense of the respiratory and of the digestive tract. Among the digestive tract, appendix, small bowel, and pancreas are the preferential sites of involvement, other locations have been more rarely reported. Neuroendocrine digestive tumors may present with various symptoms in relationship with their localization and a complex pathophysiology. Diagnosis is often made at an advanced stage, explaining partly the bad prognosis of these tumors. The optimal management of digestive neuroendocrine tumors is rendered difficult by their rarity and by a low number of randomized trials. We review the literature regarding epidemiologic and prognostic features of these rare tumors, their diagnostic and therapeutic care. Potential complications are also discussed. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  13. Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study.

    Science.gov (United States)

    Giesbrecht, Gerald F; Ejaredar, Maede; Liu, Jiaying; Thomas, Jenna; Letourneau, Nicole; Campbell, Tavis; Martin, Jonathan W; Dewey, Deborah

    2017-05-19

    Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3 month old infants. Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010-2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize changes in infant cortisol as a function of prenatal BPA exposure. Higher maternal BPA was associated with increases in baseline cortisol among females (β = 0.13 log μg/dL; 95% CI: 0.01, 0.26), but decreases among males (β = -0.22 log μg/dL; 95% CI: -0.39, -0.05). In contrast, higher BPA was associated with increased reactivity in males (β = .30 log μg/dL; 95% CI: 0.04, 0.56) but decreased reactivity in females (β = -0.15 log μg/dL; 95% CI: -0.35, 0.05). Models adjusting for creatinine yielded similar results. Prenatal BPA exposure is associated with sex-specific changes in infant HPA axis function. The biological plausibility of these findings is supported by their consistency with evidence in rodent models. Furthermore, these data support the hypotheses that sexually dimorphic changes in children's behaviour following prenatal BPA exposure are mediated by sexually dimorphic changes in HPA axis function.

  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. Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Ritter, J M; Garner, M M; Chilton, J A; Jacobson, E R; Kiupel, M

    2009-11-01

    This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.

  16. Primary Small Cell Neuroendocrine Carcinoma of Vagina: A Rare Case Report

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    Jignasa N. Bhalodia

    2011-01-01

    Full Text Available Primary small cell neuroendocrine carcinoma of vagina is an extremely rare disease. There have been only 26 previously reported cases in literature. Here, we report a case of primary small cell neuroendocrine carcinoma of vagina. Immunohistochemistry (IHC showed tumor cells positive for synaptophysin, chromogranin, and neuron-specific enolase (NSE.

  17. 131I-MIBG and neuroendocrine tumours

    International Nuclear Information System (INIS)

    Oliva Gonzalez, Juan Perfecto; Gonzalez Gonzalez, Joaquin Jorge; Calderon Marin, Carlos Fabian

    2012-01-01

    Neuroendocrine tumours are neoplasms that arise from various tissues closely linked to the neural crest by their common embryological origin. These tumours have the ability to synthesize neurotransmitter peptides and hormones, as well as to store catecholamines. Some of these tumours express somatostatin receptors at their membranes, what have allowed nuclear medicine to be involved in their diagnosis, treatment and monitoring. Since they arise from different and varied types of tissues, these tumours have a wide range of signs and symptoms different for every one of them. These signs and symptoms mainly depend on their biochemical characteristics, given by the substances they secrete, as well as by their location, and consequently, they also depend on the place where the tumour appears, its local infiltration, and potential long-distance metastasis resulting from the tumour). Neuroendocrine tumours are diagnosed by means of nuclear medicine images, which are obtained by using different techniques and radiopharmaceuticals such as 99 mTc dimercaptosuccinic acid (DMSA(V)), 99 mTc-methoxy-isobutyl-isonitrile (MIBI), metaiodobenzylguanidine (MIBG) labelled with 131 I or 123 I ( 131 I-MIBG or 123 I -MIBG), 111 In-labelled octreotide, positron emission tomography, using 68 Ga-labelled somatostatin analogues and carcinoembryonic antigen monoclonal antibodies. Nuclear medicine uses mainly somatostatin analogues labelled with 90 Y or 177 Lu for the treatment of these tumours. This paper is aimed at showing our experience in the use of 131 I-MIBG for the diagnosis and treatment of neuroendocrine tumours.(author)

  18. Maternal High-Fat Diet Programming of the Neuroendocrine System and Behavior

    Science.gov (United States)

    Sullivan, Elinor L.; Riper, Kellie M.; Lockard, Rachel; Valleau, Jeanette C.

    2015-01-01

    Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic pituitary adrenal (HPA) axis. PMID:25913366

  19. [Trauma & the reproductive lifecycle in women].

    Science.gov (United States)

    Born, Leslie; Phillips, Shauna Dae; Steiner, Meir; Soares, Claudio N

    2005-10-01

    Women are at significantly higher risk for developing post-traumatic stress disorder (PTSD) than men, resulting in increased psychosocial burden and healthcare related costs. Recent research has shown complex interactions between the impact of traumatic experiences, and the reproductive lifecycle in women. For example, women suffering from premenstrual dysphoric disorder (PMDD) who also report a history of sexual or physical abuse are more likely to present with different neuroendocrine reactivity to stressors, when compared to premenstrual dysphoric disorder subjects without prior history of trauma or abuse or non-premenstrual dysphoric disorder subjects. In addition, women with a history of abuse or trauma may experience re-emergence of symptoms during pregnancy. Lastly, females who experience miscarriage may present with even higher prevalence rates of post-traumatic stress disorder symptoms. In this manuscript we examine the existing data on gender differences in post-traumatic stress disorder, with particular focus on psychological and physiological factors that might be relevant to the development of symptoms after exposure to traumatic events associated with the reproductive life cycle. Current options available for the treatment of such symptoms, including group and counselling therapies and debriefing are critically reviewed.

  20. A Rare Case of Primary Infiltrating Neuroendocrine Carcinoma of the Breast

    International Nuclear Information System (INIS)

    Nawawi, Ouzreiah; Ying Goh, Keat; Rahmat, Kartini

    2012-01-01

    Primary neuroendocrine carcinoma of the breast is a very rare malignant tumor. There are not many cases reported in the English literature since it was first documented in 1983. Reports on the imaging features, in particular the ultrasonographic features of this rare tumor are scarce. Herein, we report a case of aggressive primary infiltrating neuroendocrine carcinoma of the breast, masquerading as an inflammatory breast condition in a 22-year-old young lady, perhaps the youngest case ever reported in the English literature. We discuss the imaging features and highlight the Doppler ultrasonographic findings of this rare breast carcinoma. This is the first documentation on Doppler ultrasonographic findings of primary neuroendocrine carcinoma of the breast in the literature

  1. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

    Science.gov (United States)

    Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

    2016-07-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

  2. 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

  3. Neuroendocrine reactivity and recovery from work with different physical and mental demands

    NARCIS (Netherlands)

    Sluiter, J. K.; Frings-Dresen, M. H.; van der Beek, A. J.; Meijman, T. F.; Heisterkamp, S. H.

    2000-01-01

    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. Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

    Directory of Open Access Journals (Sweden)

    Caroline I. E. Renner

    2015-09-01

    Full Text Available Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed.

  5. 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

  6. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

    Science.gov (United States)

    van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

    2017-01-01

    hyper-reactivity in adulthood, as also found in major depression. This hyper-activity is related to increased corticotrophin-releasing hormone signaling and impaired glucocorticoid receptor-mediated negative feedback. In contrast, initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder, and future studies should investigate its neural/neuroendocrine foundation in further detail. Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory. PMID:28469557

  7. Social stress contagion in rats: Behavioural, autonomic and neuroendocrine correlates.

    Science.gov (United States)

    Carnevali, Luca; Montano, Nicola; Statello, Rosario; Coudé, Gino; Vacondio, Federica; Rivara, Silvia; Ferrari, Pier Francesco; Sgoifo, Andrea

    2017-08-01

    The negative emotional consequences associated with life stress exposure in an individual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as "demonstrator" (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined "observer" (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between

  8. A case report of metastatic neuroendocrine carcinoma of the right adrenal gland successfully treated with chemotherapy and surgery.

    Science.gov (United States)

    Ochiai, Toshiya; Komiyama, Sosuke; Ikoma, Hisashi; Kubota, Takeshi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Kikuchi, Shojiro; Fujiwara, Hitoshi; Sakakura, Chohei; Kokuba, Yukihito; Sonoyama, Teruhisa; Otsuji, Eigo

    2010-08-01

    Poorly differentiated neuroendocrine carcinoma has a poor prognosis, especially when associated with distant metastasis. A 60-year-old man was admitted to a private hospital because of dyspnea at work in 2007. Computed tomography revealed lung infarction and a right adrenal tumor sized 12 cm in diameter that was tightly compressed against the inferior vena cava (IVC). Moreover, multiple lymph node metastases around the celiac axis and a solitary liver metastasis at the lateral segment were observed. Thus, we planned chemotherapy without surgery. We selected a combination therapy of irinotecan (CPT-11) and cisplatin (CDDP) (i.e., IP therapy): administration of CDDP [60 mg/m(2) body surface area (BSA)] on day 1 plus CPT-11 (80 mg/m(2)) BSA on days 1 and 8. Thereafter, this protocol was repeated at 3-week intervals. After 15 months of this chemotherapy strategy, the whole lesions showed a partial response by RECIST. The primary tumor had shrunk to 4.2 cm in diameter. In November 2008, we planned surgery to perform resection of the whole lesions. Histological diagnosis of the specimen was a poorly differentiated neuroendocrine carcinoma based on the immunostaining features, i.e., synaptophysin- and chromogranin positive. There were no viable tumor cells at the dissected lymph nodes or at the liver tumor. After surgery, CPT-11 administration was continued. The patient has remained well for 9 months without recurrence.

  9. Everolimus for Advanced Pancreatic Neuroendocrine Tumors.

    NARCIS (Netherlands)

    Yao, James C.; Shah, Manisha H.; Ito, Tetsuhide; Bohas, Catherine Lombard; Wolin, Edward M.; Van Cutsem, Eric; Hobday, Timothy J.; Okusaka, Takuji; Capdevila, Jaume; de Vries, Elisabeth G. E.; Tomassetti, Paola; Pavel, Marianne E.; Hoosen, Sakina; Haas, Tomas; Lincy, Jeremie; Lebwohl, David; Oberg, Kjell

    2011-01-01

    Background: Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. Methods: We randomly assigned 410

  10. Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

    Science.gov (United States)

    Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

    2012-01-01

    Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

  11. Sinonasal malignancies with neuroendocrine differentiation: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    Menon Santosh

    2010-01-01

    Full Text Available Primary sinonasal tumors with neuroendocrine differentiation (SCND are uncommon tumors with considerable overlap of histological features. Based on their neuroendocrine differentiation they can be sub categorized into sinonasal undifferentiated carcinoma (SNUC, sinonasal neuroendocrine carcinoma (SNEC, esthesioneuroblastoma (ENB and small cell carcinoma (SmCC. The natural history and biological behavior varies in this group of tumors. Hence the histo-morphological diagnosis coupled with grading/staging is important for the prognostication of these tumors. Aim : To study the clinicopathological characteristics of sinonasal neuroendocrine malignancies at our institute. Material and Methods : We searched our institute′s pathology database for the period from 2002 to 2007, for the four subcategories of sinonasal tumors with neuroendocrine differentiation. Morphological and immunohistochemical features were studied and, grading, staging was done in accordance with standard criteria. The clinical treatment and follow- up data were retrieved from the case files in available cases. Results : A total of 37 cases were retrieved from our database which include 14 cases of SNUC, 14 cases of ENB and nine cases of SNEC. The cases of SNUC were immunopositive for cytokeratin, epithelial membrane antigen and weakly for neuron-specific enolase. SNEC showed strong reactivity with epithelial and neuroendocrine markers whereas ENB demonstrated immunoreactivity to synaptophysisn and chromogranin strongly, with weak to negative expression of epithelial markers. All cases of SNUC and SNEC were of high grade and stage whereas 50% of ENB cases were of grade II but high stage tumors. Most of the SNUC and SNEC patients had been treated with multimodality treatment regimens including upfront chemotherapy followed by surgery and loco- regional radiation. In contrast, ENB patients had undergone surgical extirpation followed by radiation therapy in majority of cases. With

  12. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  13. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  14. Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

    Science.gov (United States)

    Hatton, M Q; Reed, N S

    1997-01-01

    The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity.

  15. The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

    Science.gov (United States)

    Graham, A R; Payne, C M; Nagle, R B; Angel, E

    1987-02-01

    We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

  16. Links between nutrition and reproduction in cattle

    International Nuclear Information System (INIS)

    Marie, M.

    1999-01-01

    Situations in which nutrition modulates reproductive function, and targets involved, are identified, particularly in relation to initiation of cyclicity (at puberty, during the post-partum period or after induction of ovulation), fertility and induction of ovulation. The usefulness and pertinence of measurements of body weight variations, body condition score, nutritional balance or blood metabolites (glucose, ketone bodies, free fatty acids, cholesterol, urea and amino acids) to evaluate nutritional status in this context is considered. Leptin could play a central role in causal mechanisms linking nutrition and reproduction, in conjunction with somatotropic axis, insulin, opioids, and neuropeptide Y. (author)

  17. [Melatonin secretion in women of advanced reproductive age].

    Science.gov (United States)

    Ermolenko, K S; Rapoport, S I; Solov'eva, A V

    2013-01-01

    The patient's age is a key factor determining success of in vitro fertilization. The ovarian reserve and oocyte quality are known to decrease with age. Much attention has been given recently to the role of epiphysis and its hormone, melatonin, in synchronization of daily and seasonal biorhythms in anti-stress protection and neuroregulation of reproductive processes. The aim of our work was to study melatonin levels in infertile women of reproductive age. We also measured sex hormones, anti-Mullerian hormone, FSH, and LH in blood and melatonin sulfate in urine at 8 points (RIA). Women of advanced reproductive age showed markedly reduced melatonin secretion due to functional disorders in the hypothalamic-pituitary-gonadal axis. Results of the study suggest the necessity of prescription of exogenous melatonin to the patients included in assisted reproduction programs for the improvement of their efficacy.

  18. 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

  19. Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

    Science.gov (United States)

    Wierman, Margaret E; Xu, Mei; Pierce, A; Bliesner, B; Bliss, S P; Roberson, M S

    2012-01-01

    Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron. Copyright © 2011 S. Karger AG, Basel.

  20. 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...

  1. Neuroendocrine cells during human prostate development: does neuroendocrine cell density remain constant during fetal as well as postnatal life?

    NARCIS (Netherlands)

    Xue, Y.; van der Laak, J.; Smedts, F.; Schoots, C.; Verhofstad, A.; de la Rosette, J.; Schalken, J.

    2000-01-01

    Knowledge concerning differentiation of neuroendocrine (NE) cells during development of the human prostate is rather fragmentary. Using immunohistochemistry combined with a morphometric method, we investigated the distribution and density of NE cells in the developing human prostate, with special

  2. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

    Directory of Open Access Journals (Sweden)

    Kendall Gillies

    2016-04-01

    Full Text Available Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants or qualitative (relative change from control values approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across

  3. 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.

  4. Cystic pancreatic neuroendocrine tumors (cPNETs: a systematic review and meta-analysis of case series

    Directory of Open Access Journals (Sweden)

    Luis Hurtado-Pardo

    Full Text Available Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387 were sporadic tumors and 10.3% (n = 40 corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135. Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338, and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb, and 12.2% were advanced (III-IV. Disease-free survival at 5 years in stages (I-IIIa and (IIIb-IV was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001 in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5% and multifocal (28.1% tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

  5. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  6. Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function.

    Science.gov (United States)

    Eachus, Helen; Bright, Charlotte; Cunliffe, Vincent T; Placzek, Marysia; Wood, Jonathan D; Watt, Penelope J

    2017-06-01

    Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that the role of DISC1 in stress responses is evolutionarily conserved and that DISC1 is essential for normal functioning of the HPI axis. Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. Our studies reveal that in the embryo, disc1 is expressed in neural progenitor cells of the hypothalamus, a conserved region of the vertebrate brain that centrally controls responses to environmental stressors. In disc1 mutant embryos, proliferating rx3+ hypothalamic progenitors are not maintained normally and neuronal differentiation is compromised: rx3-derived ff1b+ neurons, implicated in anxiety-related behaviours, and corticotrophin releasing hormone (crh) neurons, key regulators of the stress axis, develop abnormally, and rx3-derived pomc+ neurons are disorganised. Abnormal hypothalamic development is associated with dysfunctional behavioural and neuroendocrine stress responses. In contrast to wild type siblings, disc1 mutant larvae show altered crh levels, fail to upregulate cortisol levels when under stress and do not modulate shoal cohesion, indicative of abnormal social behaviour. These data indicate that disc1 is essential for normal development of the hypothalamus and for the correct functioning of the HPA/HPI axis. © The Author 2017. Published by Oxford University Press.

  7. Small cell neuroendocrine carcinoma of the endometrium, a rare aggressive tumor

    International Nuclear Information System (INIS)

    Rajab, Khalil E.; Sandhu, Amarjit K.; Rajeswari, Mangla S.; Malik, A.

    2005-01-01

    This is a report of a young infertile woman with a history of 8 years amenorrhea, who presented with history of vaginal bleeding of 2 months duration. Investigations revealed a small cell neuroendocrine carcinoma of the endometrium, which penetrated half of the thickness of uterine wall. We have described the clinical progress and management of this rare and highly malignant cancer. A review of the pathological types and behavior of clear cell neuroendocrine carcinoma is presented. (author)

  8. 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.

  9. Similar cold stress induces sex-specific neuroendocrine and working memory responses.

    Science.gov (United States)

    Solianik, Rima; Skurvydas, Albertas; Urboniene, Daiva; Eimantas, Nerijus; Daniuseviciute, Laura; Brazaitis, Marius

    2015-01-01

    Men have higher cold-induced neuroendocrine response than women; nevertheless, it is not known whether a different stress hormone rise elicits different effects on cognition during whole body cooling. The objective was to compare the effect of cold-induced neuroendocrine responses on the performance of working memory sensitive tasks between men and women. The cold stress continued until rectal temperature reached 35.5 degree C or for a maximum of 170 min. Working memory performance and stress hormone concentrations were monitored. During cold stress, body temperature variables dropped in all subjects (P < 0.001) and did not differ between sexes. Cold stress raised plasma epinephrine and serum cortisol levels only in men (P < 0.05). Cold stress adversely affected memory performance in men but not in women (P < 0.05). The present study indicated that similar moderate cold stress in men and women induces sex-specific neuroendocrine and working memory responses.

  10. 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

  11. Research progress on the role of melatonin and its receptors in animal reproduction: A comprehensive review.

    Science.gov (United States)

    Talpur, H S; Chandio, I B; Brohi, R D; Worku, T; Rehman, Z; Bhattarai, D; Ullah, F; JiaJia, L; Yang, L

    2018-04-16

    Melatonin and its receptors play a crucial role in the regulation of the animal reproductive process, primarily in follicular development. However, the role that melatonin performs in regulating hormones related with reproduction remains unclear. Melatonin and its receptors are present both in female and male animals' organs, such as ovaries, heart, brain and liver. Melatonin regulates ovarian actions and is a key mediator of reproductive actions. Melatonin has numerous effects on animal reproduction, such as protection of gametes and embryos, response to clock genes, immune-neuroendocrine, reconciliation of seasonal variations in immune function, and silence or blockage of genes. The growth ratio of reproductive illnesses in animals has raised a remarkable concern for the government, animal caretakers and farm managers. In order to resolve this challenging issue, it is very necessary to conduct state-of-the-art research on melatonin and its receptors because melatonin has considerable physiognomies. This review article presents a current contemporary research conducted by numerous researchers from the entire world on the role of melatonin and its receptors in animal reproduction, from the year 1985 to the year 2017. Furthermore, this review shows scientific research challenges related to melatonin receptors and their explanations based on the findings of 172 numerous research articles, and also represents significant proficiencies of melatonin in order to show enthusiastic study direction for animal reproduction researchers. © 2018 The Authors. Reproduction in Domestic Animals Published by Blackwell Verlag GmbH.

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

    Directory of Open Access Journals (Sweden)

    Lutz Kockel

    2016-10-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Specific targeting for the treatment of neuroendocrine tumors; Ciblage specifique pour le traitement des tumeurs neuro-endocrines

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. [Netherlands Cancer Institute 1066 CX Amsterdam, Dept. of Nuclear Medicine (Netherlands)

    2003-09-01

    For the treatment of neuroendocrine tumors three ways of specific targeting of radionuclides prevail: by {sup 131}I-meta-iodo-benzyl-guanidine (MIBG), which is taken up by an active uptake-1 mechanism and stored in neurosecretory granules of neural crest tumor cells, by radiolabeled peptides, in particular the somatostatin analogs octreotide and lanreotide, targeting the peptide receptors, and by radiolabeled antibodies, which target tumor cell surface antigens. The choice depends on the indication, the results of diagnostic imaging using tracer amounts of these agents, the availability and feasibility of radionuclide therapy and of other treatment modalities. The applications, clinical results and developments for the major indications are reviewed. {sup 131}I-MIBG therapy has a cumulative response rate of 50%, associated with little toxicity, in metastatic pheochromocytoma, paraganglioma and neuroblastoma, whereas its role is primarily palliative in patients with medullary thyroid carcinoma and carcinoid tumors. Treatment using {sup 90}Y- or {sup 177}Lu-labeled octreotide/lanreotide is mostly used in neuroendocrine gastro-entero-pancreatic (GEP) tumors and paraganglioma, attaining stabilization of disease anti-palliation in the majority of patients. As this treatment is specific for the receptor rather than for the tumor type, it may also be applicable to other, non-neuroendocrine tumors. Radioimmunotherapy is applied in medullary thyroid carcinoma, in which a phase I/II study using bi-specific anti-DTPA/anti-CEA immuno-conjugates followed by {sup 131}I-hapten has proven some degree of success, and may be used in neuroblastoma more effectively than before, once chimeric and humanized monoclonal antibodies become available for therapy. Integration of these specific and noninvasive therapies at an optimal moment into the treatment protocols of these diseases may enhance their effectiveness and acceptance. (author)

  15. Transcriptional regulatory dynamics of the hypothalamic-pituitary-gonadal axis and its peripheral pathways as impacted by the 3-beta HSD inhibitor Trilostane in zebrafish (Danio rerio)

    Science.gov (United States)

    To identify transcription factors (TFs), members of hypothalamic-pituitary- gonadal axis (HPG-axis), TF networks and signaling pathways underlying generalized effects of 3-beta hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exp...

  16. Clinical application of 99mTc-HYNIC-TOC SPECT/CT in diagnosing and monitoring of pancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Xu, Junyan; Li, Yi; Xu, Xiaoping; Zhang, Jiangang; Zhang, Yingjian; Yu, Xianjun; Huang, Dan

    2018-06-20

    Our aim of this research was to determine the value of SPECT/CT with 99m Tc-HYNIC-TOC for evaluation of the pancreatic masses which were suspected as neuroendocrine neoplasms and follow-up of patients with pancreatic neuroendocrine neoplasms. We retrospectively analyzed 184 patients who performed 99m Tc-HYNIC-TOC SPECT/CT. All the patients were divided into two groups: one for assessment of diagnostic efficiency for pancreatic suspected masses (n = 140) and another for monitoring recurrence after surgery (n = 44). The image findings acquired at 2 h postinjection were compared to final diagnoses from pathological results and clinical follow-up. Then, the correlation between ratios of tumor-to-background (TBR) and tumor grade was analyzed. In group 1, 95/140 (67.9%) patients were confirmed as neuroendocrine neoplasms including 85 neuroendocrine tumors and 10 neuroendocrine carcinomas. Patient-based analysis showed that the sensitivity, specificity and accuracy of diagnosing neuroendocrine neoplasms with SPECT/CT were 81.1, 84.4 and 82.1%. There was significant difference of TBRs among G1, G2 and G3 (F = 3.175, P = 0.048). In group 2, 22/44 (50.0%) patients occurred metastasis mainly in liver. The sensitivity, specificity and accuracy of monitoring recurrence were 87.0, 100 and 93.2%. 99m Tc-HYNIC-TOC SPECT/CT is a reliable method of diagnosing and monitoring of pancreatic neuroendocrine neoplasms, especially neuroendocrine tumors.

  17. Super-resolution microscopy in studying neuroendocrine cell function

    Directory of Open Access Journals (Sweden)

    Anneka eBost

    2013-11-01

    Full Text Available The last two decades have seen a tremendous development in high resolution microscopy techniques giving rise to acronyms such as TIRFM, SIM, PALM, STORM, and STED. The goal of all these techniques is to overcome the physical resolution barrier of light microscopy in order to resolve precise protein localization and possibly their interaction in cells. Neuroendocrine cell function is to secrete hormones and peptides on demand. This fine-tuned multi-step process is mediated by a large array of proteins. Here, we review the new microscopy techniques used to obtain high resolution and how they have been applied to increase our knowledge of the molecular mechanisms involved in neuroendocrine cell secretion. Further the limitations of these methods are discussed and insights in possible new applications are provided.

  18. Thirty-five years of assisted reproductive technologies in Israel

    Directory of Open Access Journals (Sweden)

    Daphna Birenbaum-Carmeli

    2016-06-01

    Full Text Available Israel is known as a pronatalist country. Whether due to the Biblical commandment to ‘be fruitful and multiply’ or the traumas of the Holocaust and perennial wars, reproduction is a central life goal for most Israelis. Israeli women bear substantially more children than their counterparts in industrialized countries and view child-rearing as a key life accomplishment. These personal world-view and real-life individual quests take place in a context of equally pronatalist state policies and religious openness to assisted reproductive technologies. In this paper, I outline 35 years of assisted reproductive technologies in Israel by tracing a principal axis in the development of three major technologies of assisted reproduction: the proliferation of IVF-ICSI; the globalization of gamete donation; and the privatization of surrogacy. The paper is based on a policy analysis as well as various studies of assisted reproductive technologies, conducted in Israel over this period.

  19. Seasonal variation in hormonal responses of timber rattlesnakes (Crotalus horridus) to reproductive and environmental stressors.

    Science.gov (United States)

    Lutterschmidt, William I; Lutterschmidt, Deborah I; Mason, Robert T; Reinert, Howard K

    2009-08-01

    Data addressing adrenocortical modulation across taxonomic groups are limited, especially with regard to how female reproductive condition influences the sensitivity of the hypothalamus-pituitary-adrenal axis. We investigated seasonal and reproductive variation in basal and stress-induced hormone profiles in a population of free-ranging timber rattlesnakes (Crotalus horridus) in north-central Pennsylvania during spring (i.e., May), summer (i.e., July), and early fall (i.e., September). Baseline corticosterone concentrations varied seasonally and were significantly lower during the summer sampling period in July. We observed a significant negative relationship between baseline corticosterone and testosterone in male snakes, while baseline corticosterone and estradiol tended to be positively correlated in females. Treatment of snakes with 1 h of capture stress significantly increased corticosterone across all seasons. However, there was a significant interaction between corticosterone responses to capture stress and season, suggesting that adrenocortical function is modulated seasonally. Because elevated corticosterone may be associated with reproduction, we asked whether hormonal stress responses vary with female reproductive condition. Although sample sizes are low, reproductive snakes had significantly higher baseline and stress-induced corticosterone concentrations than non-reproductive or post-parturient females. Further, despite similar baseline corticosterone concentrations between non-reproductive and post-parturient rattlesnakes, post-parturient females responded to capture stress with a significantly higher increase in corticosterone. Collectively, these data suggest that the sensitivity of the hypothalamus-pituitary-adrenal axis varies both seasonally and with changing reproductive states.

  20. Predicting Adaptive Response to Fadrozole Exposure:Computational Model of the Fathead MinnowsHypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (...

  1. Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence.

    Science.gov (United States)

    Shahanoor, Ziasmin; Sultana, Razia; Baker, Madelyn R; Romeo, Russell D

    2017-12-01

    Adolescence is associated with the maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress response. Adolescence is also a period in development marked by a variety of stress-related vulnerabilities, including psychological and physiological dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA axis. In adult mice, a model of disrupted HPA function has been developed using oral chronic corticosterone administration via the drinking water, which results in various physiological and neurobehavioral abnormalities, including changes in stress reactivity and anxiety-like behaviors. In an effort to further complement and extend this model, we tested the impact of HPA disruption in adolescent mice. We also examined whether this disruption led to different outcomes depending on whether the treatment happened during adolescence or adulthood. In the current set of experiments, we exposed adult (70days of age) or adolescent (30days of age) male C57BL/6N mice to 4 weeks of either 0 or 25μg/ml oral corticosterone via their drinking water. We measured body weight during treatment and plasma corticosterone levels and activation of the paraventricular nucleus (PVN), as indexed by FOS immunohistochemistry, before and after a 30min session of restraint stress. Our data indicate that adolescent animals exposed to chronic corticosterone showed weight loss during treatment, an effect not observed in adults. Further, we found stress failed to elevate plasma corticosterone levels in treated mice, regardless of whether exposure occurred in adulthood or adolescence. Despite this reduced hormonal responsiveness, we found significant neural activation in the PVN of both adult- and adolescent-treated mice, indicating a dissociation between stress-induced peripheral and central stress responses following chronic corticosterone exposure. Moreover, stress-induced neural activation in the PVN was unaffected

  2. Kisspeptins and RFRP-3 act in concert to synchronize rodent reproduction with seasons

    Directory of Open Access Journals (Sweden)

    Valerie eSimonneaux

    2013-02-01

    Full Text Available Seasonal mammals use the photoperiodic variation in the nocturnal production of the pineal hormone melatonin to synchronize their reproductive activity with seasons. In rodents, the short day profile of melatonin secretion has long been proven to inhibit reproductive activity. Lately, we demonstrated that melatonin regulates the expression of the hypothalamic peptides kisspeptins (Kp and RFamide-related peptide-3 (RFRP-3, recently discovered as potent regulators of GnRH neuron activity. In the male Syrian hamster, Kp expression in the arcuate nucleus is down-regulated by melatonin independently of the inhibitory feedback of testosterone. A central or peripheral administration of Kp induces an increase in pituitary gonadotropins and gonadal hormone secretion, but most importantly a chronic infusion of the peptide reactivates the photoinhibited reproductive axis of Syrian hamsters kept in short day conditions. RFRP-3 expression in the dorsomedial hypothalamus is also strongly inhibited by melatonin in a short day photoperiod. Although RFRP-3 is usually considered as an inhibitory component of the gonadotropic axis, a central acute administration of RFRP-3 in the male Syrian hamster induces a marked increase in gonadotropin secretion and testosterone production. Furthermore, a chronic central infusion of RFRP-3 in short day-adapted hamsters reactivates the reproductive axis, in the same manner as Kp. Both Kp and RFRP-3 neurons project onto GnRH neurons and both neuropeptides regulate GnRH neuron activity. In addition, central RFRP-3 infusion was associated with a significant increase in arcuate Kp expression. However, the actual sites of action of both peptides in the Syrian hamster brain are still unknown. Altogether our findings indicate that Kp and RFRP neurons are pivotal relays for the seasonal regulation of reproduction, and also suggest that RFRP neurons might be the primary target of the melatoninergic message.

  3. 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 ...

  4. Mechanical stress induces neuroendocrine and immune responses of sea cucumber ( Apostichopus japonicus)

    Science.gov (United States)

    Tan, Jie; Li, Fenghui; Sun, Huiling; Gao, Fei; Yan, Jingping; Gai, Chunlei; Chen, Aihua; Wang, Qingyin

    2015-04-01

    Grading procedure in routine sea cucumber hatchery production is thought to affect juvenile sea cucumber immunological response. The present study investigated the impact of a 3-min mechanical perturbation mimicking the grading procedure on neuroendocrine and immune parameters of the sea cucumber Apostichopus japonicus. During the application of stress, concentrations of noradrenaline and dopamine in coelomic fluid increased significantly, indicating that the mechanical perturbation resulted in a transient state of stress in sea cucumbers. Coelomocytes concentration in coelomic fluid increased transiently after the beginning of stressing, and reached the maximum in 1 h. Whereas, coelomocytes phagocytosis at 3 min, superoxide anion production from 3 min to 0.5 h, acid phosphatase activity at 0.5 h, and phenoloxidase activity from 3 min to 0.5 h were all significantly down-regulated. All of the immune parameters recovered to baseline levels after the experiment was conducted for 8 h, and an immunostimulation occurred after the stress considering the phagocytosis and acid phosphatase activity. The results suggested that, as in other marine invertebrates, neuroendocrine/immune connections exist in sea cucumber A. japonicus. Mechanical stress can elicit a profound influence on sea cucumber neuroendocrine system. Neuroendocrine messengers act in turn to modulate the immunity functions. Therefore, these effects should be considered for developing better husbandry procedures.

  5. 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.

  6. Characterization and differential expression of three GnRH forms during reproductive development in cultured turbot Schophthalmus maximus

    Science.gov (United States)

    Zhao, Chunyan; Xu, Shihong; Feng, Chengcheng; Liu, Yifan; Yang, Yang; Wang, Yanfeng; Xiao, Yongshuang; Song, Zongcheng; Liu, Qinghua; Li, Jun

    2017-10-01

    Turbots (Schophthalmus maximus), one of the most important economic marine flatfish species, fail to undergo final spawning and spermiation naturally under artificial farming conditions. In vertebrates, reproduction is regulated by the brain-pituitary-gonadal axis (BPG-axis), and gonadotropin releasing hormone (GnRH) is one of its key components. Therefore, to better understand the physiology of reproduction in the turbot, three of the genes encoding GnRH subtypes—sbGnRH, cGnRH-II and sGnRH—were cloned and sequenced by isolating the cDNA sequences. The localizations and patterns of expression of their mRNAs were also evaluated during seasonal gonadal development. All three mRNAs were expressed abundantly in the brain; sbGnRH and sGnRH mRNAs were also detected in the gonads and pituitary gland, and sbGnRH expression was much higher than that of sGnRH, indicating the critical role of sbGnRH in regulating the BPG-axis. Moreover, the brain expression patterns of sbGnRH and sGnRH mRNAs showed an increased trend during gonadal development, peaking in mature stages. This indicated the direct regulation of gonadal development by the GnRH system. In addition, cGnRH-II mRNA expression showed no significant variations, suggesting that cGnRH-II is not critically involved in the control of reproduction. Further, the mRNA abundances of the three GnRH forms in the breeding season were significantly higher than those in immature and post-breeding stages in all analyzed brain areas. Therefore, we propose that sbGnRH is the most important hormone for the regulation of reproduction in turbot via the BPG-axis. These results will help in better understanding the reproductive endocrine mechanisms of turbots and lay the groundwork for additional studies aimed at comparing the reproductive physiology of wild individuals with those raised under artificial conditions.

  7. Predicting Adaptive Response to Fadrozole Exposure: Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (...

  8. Environment, human reproduction, menopause, and andropause.

    OpenAIRE

    Vermeulen, A

    1993-01-01

    As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripher...

  9. Neuroendocrine tumor of vulva: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Sheikh Zahoor

    2010-01-01

    Full Text Available Neuroendocrine tumor (Merkel cell carcinoma-MCC of the vulva is a very rare entity with less than 15 cases reported in the English literature. It is known for its aggressive behaviour and propensity for early dissemination. The actual cell of origin and etiology of this disease is controversial. In absence of any definite guidelines for management (due to its rarity, extrapolation of data from extra-vulvar MCC seems logical. We present a case of vulvar neuroendocrine tumor who presented at a locally advanced stage.

  10. Place of surgical resection in the treatment strategy of gastrointestinal neuroendocrine tumors.

    Science.gov (United States)

    Gaujoux, Sébastien; Sauvanet, Alain; Belghiti, Jacques

    2012-09-01

    Neuroendocrine tumors (NET) are usually slow-growing neoplasms carrying an overall favorable prognosis. Surgery, from resection to transplantation, remains the only potential curative option for these patients, and should always be considered. Nevertheless, because of very few randomized controlled trials available, the optimal treatment for these patients remains controversial, especially regarding the place of surgery. We herein discuss the place of surgical resection in the treatment strategy in neuroendocrine tumors of the digestive tract.

  11. Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment

    International Nuclear Information System (INIS)

    Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

    2016-01-01

    Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic–pituitary–gonadal–liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic

  12. EFFECT OF ADRENALECTOMY ON PROLACTIN SECRETION IN PRIMIPAROUS AND MULTIPAROUS LACTATING RATS

    Directory of Open Access Journals (Sweden)

    C. D. C. Sanches

    2018-04-01

    Full Text Available The adenohypophysis produces among other hormones prolactin, which plays an important role in reproduction, especially on the mammary glands and lactation of mammals. Prolactin is tonically controlled by tufo-infundibular dopamine, but several studies indicate that prolactin secretion is altered by the action of glucocorticoids and, therefore, is related to stress. However, the exact contribution of corticosteroids in the control of prolactin secretion is poorly understood. On the other hand, it is also known that reproductive experience can modify prolactin secretion by adenohypophysis. Thus, the present study aims to study the hormonal relationships of the hypothalamic-pituitary-adrenal axis, in particular, the glucocorticoid relationship on prolactin secretion as a function of the reproductive experience in females during lactation. The results show that reproductive experience may be a factor modifying the sensitivity of the neuroendocrine response of prolactin secretion to glucocorticoids. However, more studies are needed to understand the possible mechanisms involved, as well as possible modifications in this response as a function of the reproductive status of the females.

  13. Leptin and Reproduction: Past Milestones, Present Undertakings and Future Endeavors

    Science.gov (United States)

    Chehab, Farid F.

    2014-01-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B and dynorphin and that could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that AgRP/NPY neurons project onto GnRH and kisspeptin neurons, allowing a crosstalk between food intake and reproduction. Finally, whereas puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. Mechanisms underlying leptin resistance in pregnancy have lagged, however the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the next decade to shed new light on these complex and essential pathways. PMID:25118207

  14. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants.

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    Ana Cristina Resende Camargos

    Full Text Available Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001, adiponectin (p = 0.0007 and BDNF (p = 0.003, and serum cortisol (p = 0.048 were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS (p = 0.004, and catalase (p = 0.045 and superoxide dismutase activity (p = 0.02 were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed.

  15. 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 ...

  16. A case of giant prolactinoma, initially misdiagnosed as sinonasal neuroendocrine carcinoma

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    Yasaman Mohtasebi, M.D.

    2015-09-01

    Full Text Available Giant prolactinomas are defined as pituitary tumors greater than 4 cm, often associated with very high prolactin level (>1000 ng/mL. They are relatively rare tumors and can present differently from typical prolactinomas. They can be highly invasive, resulting in acute neurological complication at the time of presentation. We present a case of a young woman with giant prolactinoma initially misdiagnosed as sinonasal neuroendocrine carcinoma. The acute presentation of headache, ptosis and impending brain herniation, requiring emergent ventriculostomy and intubation, led to the clinical suspicion of a more sinister diagnosis. Transnasal biopsy of the mass was consistent with sinonasal neuroendocrine carcinoma, and chemotherapy was planned. Laboratory testing, however, revealed an elevated prolactin (27,400 ng/mL, after 1:100 dilution. Re-review of pathology with additional immunohistochemical staining was requested and confirmed the diagnosis of prolactinoma. After 5 months of cabergoline treatment, prolactin level has decreased to 118 ng/mL. There has been a marked reduction in tumor size and an almost complete resolution of neurological symptoms. Given their atypical presentation and potential for sharing common immunohistochemical stains with other neuroendocrine neoplasms, giant prolactinomas extending into the nasal cavity can be misdiagnosed as other neuroendocrine neoplasms which may develop at this site. Accurate diagnosis is imperative to prevent unnecessary surgery and/or radiation and to ensure implementation of dopamine agonist therapy.

  17. The nature of neuroendocrine abnormalities in depression: a controversial issue in contemporary psychiatry.

    Science.gov (United States)

    von Zerssen, D; Berger, M; Dose, M; Doerr, P; Krieg, C; Bossert, S; Riemann, D; Pirke, K M; Dolhofer, R; Müller, O A

    1986-01-01

    Neuroendocrine abnormalities in depression have been regarded, by many authors, as relatively specific markers of nosological subtypes of the disorder, e.g. primary vs. secondary, endogenous vs. non-endogenous or unipolar vs. bipolar depression. They should reflect the same changes in central neurotransmitters (e.g. noradrenergic insufficiency and/or cholinergic hyperactivity) that were hypothesized as the cause of clinical symptoms. This view is challenged on the basis of our own neuroendocrine investigations in 317 psychiatric patients and 103 normal controls. According to these studies the abnormalities are nosologically rather unspecific. They are induced by a large variety of factors, e.g. emotional stress associated with the clinical symptomatology, weight loss due to malnutrition as a consequence of reduced appetite, medication and drug withdrawal. Stress-induced hypercortisolism appears to be the most common abnormality that may trigger other neuroendocrine dysfunctions, such as a blunted TSH response to TRH. Differences in neuroendocrine abnormalities of depressives are probably due to variations in the manifold factors influencing the hormonal axes involved, to temporal changes in hormonal patterns (e.g. one abnormality triggering another) and to individual differences in the basic activity and the responsiveness of the various axes.

  18. Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

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    Xin eDu

    2015-03-01

    Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

  19. Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells.

    Science.gov (United States)

    Aumüller, G; Leonhardt, M; Renneberg, H; von Rahden, B; Bjartell, A; Abrahamsson, P A

    2001-02-01

    The neuroendocrine cells of the human prostate have been related to proliferative disorders such as prostatic cancer. Their origin, distribution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. Prostatic tissue specimens (n = 20) from human fetuses (n = 8), prepubertal and pubertal children (n = 8) and mature men (n = 4) were studied immunohistochemically using antibodies directed against neuroendocrine, epithelial as well as secretory markers. Semiquantitative computer-assisted evaluation of different epithelial and stromal components based on stereological principles was performed on azan-stained sections representative of all developmental stages. By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely associated with the formation of urethral prostatic buds. The fetal and postnatal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular peripheral acini. In peripheral ducts, the distribution is random. Maturation of the NE cells precedes that of the secretory cells by about 10-16 years. A second prostatic stem cell lineage, different from the urogenital sinus (UGS)-lineage is hypothesized originating from immature neuroendocrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. Their presence is apparently important for proliferation regulation of the UGS-derived lineage of the prostate. Copyright 2001 Wiley-Liss, Inc.

  20. 99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

    Science.gov (United States)

    Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

    2015-05-01

    The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

  1. 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.

  2. Large-Cell Neuroendocrine Carcinoma of the Esophagus: A Case from Saudi Arabia

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    Hadi Kuriry

    2015-10-01

    Full Text Available Neuroendocrine carcinomas of the esophagus are very rare, and the majority are high grade (poorly differentiated. They occur most frequently in males in their sixth and seventh decades of life. There have been no concrete data published on clinical features or on prognosis. We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 66-year-old Saudi female with progressive dysphagia and weight loss. Upper endoscopy revealed an esophageal ulcerated mass.

  3. [Neuroendocrine tumors of gastrointestinal tract: the paradigm that lasts].

    Science.gov (United States)

    Bjelović, Milos M; Babić, Tamara D

    2013-01-01

    Historically, the tumors that were morphologically different and clinically less agressive than the more common gastrointestinal adenocarcinomas were clasified under carcinoid tumors. However, the development of molecular biology tehniques revealed the heterogeneity of these tumors on cellular and subcellular level and ther different biological behaviour. Neuroendocrine tumors of gastrointestinal tract originated from neuroendocrine cells scaterred across the gastrointestinal mucosa. As a result these tumors were capable of secreting many different neurotransmiters, which may or may not be biologically active. The incidence of gastrointestinal NETs has been incresing over the last 2 to 3 decades. Patients often presented with vague, nonspecific symptoms which resulted in delayed diagnosis and adequate treatment. In this article, we discuss the nature of gastrointestinal NETs, clinical presentation, treatment options and prognosis.

  4. Carcinoid Syndrome and Carcinoid Heart Disease as Manifestations of Non-Metastatic Ovarian Neuroendocrine Tumour

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    Joana Simões-Pereira

    2017-05-01

    Full Text Available The carcinoid syndrome is rare but it is associated with carcinoid heart disease in more than a half of the cases. Carcinoid heart disease is typically characterised by morphological and functional modifications of right-sided valves. Its aetiology is probable multifactorial but serotonin appears to play a key role in the development of this valvular disease. Unlike gastrointestinal neuroendocrine tumours, ovarian neuroendocrine tumours can present with carcinoid syndrome and carcinoid heart disease in the absence of liver metastases; such ovarian neuroendocrine tumours are a unique clinical entity. The additional burden of cardiac impairment in these patients represents a significant reduction in survival. Early recognition and surgical valve replacement before advanced heart failure is established may improve the clinical outcome. We report the case of a woman with an ovarian neuroendocrine tumour and highly symptomatic carcinoid heart disease who was submitted to tumour resection followed by valvuloplasty. She demonstrated an outstanding clinical improvement and has remained free of tumour and symptomatology.

  5. [Leptin--an interim evaluation].

    Science.gov (United States)

    Bodner, J; Ebenbichler, C F; Lechleitner, M; Ritsch, A; Sandhofer, A; Gander, R; Wolf, H J; Huter, O; Patsch, J R

    1998-03-27

    The discovery of leptin, the product of the obese (ob)-gene, has broadened the horizons of research on energy balance. This hormone, produced and secreted by adipose tissue and some placental cells, finds its way to the hypothalamus, where it binds to the leptin receptors and signals satiety through the neuroendocrine axis. The fact that adipose tissue is not merely a storage depot, but also an important endocrine tissue, has revived the interest in the "lipostatic" theory of body fat regulation and has initiated many research efforts in the field of obesity, anorexia nervosa, bulimia, reproduction and haematology.

  6. Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

    Science.gov (United States)

    Naert, Gaelle; Ixart, Guy; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2011-01-01

    Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Role of leptin in female reproduction.

    Science.gov (United States)

    Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

    2015-01-01

    Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

  8. 60 YEARS OF NEUROENDOCRINOLOGY: The structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris.

    Science.gov (United States)

    Watts, Alan G

    2015-08-01

    In November 1955, Geoffrey Harris published a paper based on the Christian A Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore, MD, USA. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing so, Harris introduced a set of properties that helped define the neuroendocrine hypothalamus. They included: i) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; ii) an analogy between the representation of body parts in the sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and iii) the idea that neuroendocrine neurons are motor neurons and the pituitary stalk functions as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons must pass in order to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries that were being made in the early 1950s were beginning to influence neuroendocrinology? This Thematic Review discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and, within this framework, how novel and powerful techniques are currently taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. © 2015 Society for Endocrinology.

  9. 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.

  10. Diagnosis, treatment and prognosis of neuroendocrine tumor in stomach and duodenum

    Directory of Open Access Journals (Sweden)

    Xiang-yao WANG

    2016-04-01

    Full Text Available Objective  To investigate the clinicopathological characteristics and prognosis of patients with neuroendocrine tumor in stomach and duodenum for early diagnosis. Methods  The clinical, endoscopic and pathological data of 20 patients admitted to the PLA General Hospital from Jan. 2012 to Jan. 2015 and diagnosed as gastric and duodenal neuroendocrine tumor were collected for retrospective analysis. The histopathological classification of the disease was made according to the WHO 2010 Classification of the Neuroendocrine Neoplasms. Result  Ten male and 10 female patients aged between 35 and 77 (mean 55.5±10.6 years old were recruited in the present study. Tumor located in the stomach in 13 cases, and in duodenum in 7 cases. The maximum diameter of the tumor was 0.2-2.5cm. Endoscopic features included polypoid protrusion, hemispheric submucosal protrusion, and mucosal erosion. All the patients were treated endoscopically, among them, four patients were treated with electrocoagulation and electrosection, 10 by endoscopic resection (EMR, and 6 by endoscopic submucosal dissection (ESD. In one patient, surgical excision was done after ESD. Biopsy under gastroscopy and endoscopic ultrasonography were conducive to the diagnosis and treatment. According to the histopathological classification, 19 cases were classified as NET grade 1, and another one as NET grade 2. The follow-up study showed no metastasis and recurrence. Conclusions  The early diagnosis and treatment for gastric and duodenal neuroendocrine tumor can lead to satisfactory results. DOI: 10.11855/j.issn.0577-7402.2016.03.12

  11. 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

  12. Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

    Science.gov (United States)

    Marshall, P E; Goldsmith, P C

    1980-07-14

    The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.

  13. Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide-Related Peptides and LPXRFamide Peptides, in the Hypothalamic–Pituitary–Gonadal Axis

    Directory of Open Access Journals (Sweden)

    Takayoshi Ubuka

    2018-01-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a hypothalamic neuropeptide that decreases gonadotropin synthesis and release by directly acting on the gonadotrope or by decreasing the activity of gonadotropin-releasing hormone (GnRH neurons. GnIH is also called RFamide-related peptide in mammals or LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The primary receptor for GnIH is GPR147 that inhibits cAMP production in target cells. Although most of the studies in mammals, birds, and fish have shown the inhibitory action of GnIH in the hypothalamic–pituitary–gonadal (HPG axis, several in vivo studies in mammals and many in vivo and in vitro studies in fish have shown its stimulatory action. In mouse, although the firing rate of the majority of GnRH neurons is decreased, a small population of GnRH neurons is stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH release in the breeding season when their endogenous LH level is high but stimulates LH release in non-breeding season when their LH level is basal. Besides different effects of GnIH on the HPG axis depending on the reproductive stages in fish, higher concentration or longer duration of GnIH administration can stimulate their HPG axis. These results suggest that GnIH action in the HPG axis is modulated by sex-steroid concentration, the action of neuroestrogen synthesized by the activity of aromatase stimulated by GnIH, estrogen membrane receptor, heteromerization and internalization of GnIH, GnRH, and estrogen membrane receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have a physiological role to maintain reproductive homeostasis according to developmental and reproductive stages.

  14. The relation between work-induced neuroendocrine reactivity and recovery, subjective need for recovery, and health status

    NARCIS (Netherlands)

    Sluiter, JK; Frings-Dresen, MHW; van der Beek, AJ; Meijman, TF

    Objectives: The purpose of this cross-sectional study with repeated measurements was to find out to what extent neuroendocrine reactivity during work and neuroendocrine recovery from work, and work characteristics, are related to subjective need for recovery and perceived health status. Methods:

  15. Marijuana, the Endocannabinoid System and the Female Reproductive System.

    Science.gov (United States)

    Brents, Lisa K

    2016-06-01

    Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.

  16. Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

    2004-07-01

    Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

  17. 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

    Science.gov (United States)

    Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

    2017-06-01

    Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

  18. Reproduction elevates the corticosterone stress response in common fruit bats.

    Science.gov (United States)

    Klose, Stefan M; Smith, Carolynn L; Denzel, Andrea J; Kalko, Elisabeth K V

    2006-04-01

    Changes in reproductive state or the environment may affect the sensitivity of the hypothalamic-pituitary-andrenal (HPA) axis. However, little is known about the dynamics of the resulting corticosteroid stress response, in particular in tropical mammals. In this study, we address the modulation of corticosterone release in response to different reproductive conditions and seasonality in 326 free-living common fruit-eating bats (Artibeus jamaicensis) on Barro Colorado Island in Panama during dry and wet seasons. We present strong evidence that stress sensitivity is primarily modulated by reproductive condition. In reproductively active females, corticosterone increases were more rapid and reached higher levels, but also decreased significantly faster than in inactive females. The corticosterone response was weaker in reproducing males than in females and delayed compared to non-reproductive males. Testes volume in reproductively active males was negatively correlated with corticosterone concentrations. Our findings suggest differentiated dynamics in the corticosterone stress response between sexes, potentially reflecting conflicting ecological demands. In females, a strong acute corticosterone response may represent high stress- and risk-sensitivity that facilitates escape and thus helps to protect reproduction. In males, suppression during reproductive activity could reflect lowered stress sensitivity to avoid chronically elevated corticosterone levels in times of frequent aggressive and therefore costly inter-male encounters.

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

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    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.

  20. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

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    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  1. Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

    Science.gov (United States)

    Claimon, Apichaya; Chuthapisith, Suebwong; Samarnthai, Norasate; Pusuwan, Pawana

    2015-08-01

    The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

  2. Increased expression of alpha- and beta-globin mRNAs at the pituitary following exposure to estrogen during the critical period of neonatal sex differentiation in the rat

    DEFF Research Database (Denmark)

    Leffers, H; Navarro, V M; Nielsen, John E

    2006-01-01

    Deterioration of reproductive health in human and wildlife species during the past decades has drawn considerable attention to the potential adverse effects of exposure to xenosteroids during sensitive periods of sex development. The hypothalamic-pituitary (HP) unit is a key element in the neuroe......Deterioration of reproductive health in human and wildlife species during the past decades has drawn considerable attention to the potential adverse effects of exposure to xenosteroids during sensitive periods of sex development. The hypothalamic-pituitary (HP) unit is a key element...... in the neuroendocrine system controlling development and function of the reproductive axis; the HP unit being highly sensitive to the organizing effects of endogenous and exogenous sex steroids. To gain knowledge on the molecular mode of action and potential biomarkers of exposure to estrogenic compounds at the HP unit......-specific biomarkers of exposure to estrogenic (and/or anti-androgenic) compounds at critical periods of sex development, whose potential in the assessment of endocrine disrupting events at the HP unit merits further investigation....

  3. The Development of Neuroendocrine Disturbances over Time: Longitudinal Findings in Patients after Traumatic Brain Injury and Subarachnoid Hemorrhage

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    Anna Kopczak

    2015-12-01

    Full Text Available Previous reports suggest that neuroendocrine disturbances in patients with traumatic brain injury (TBI or aneurysmal subarachnoid hemorrhage (SAH may still develop or resolve months or even years after the trauma. We investigated a cohort of n = 168 patients (81 patients after TBI and 87 patients after SAH in whom hormone levels had been determined at various time points to assess the course and pattern of hormonal insufficiencies. Data were analyzed using three different criteria: (1 patients with lowered basal laboratory values; (2 patients with lowered basal laboratory values or the need for hormone replacement therapy; (3 diagnosis of the treating physician. The first hormonal assessment after a median time of three months after the injury showed lowered hormone laboratory test results in 35% of cases. Lowered testosterone (23.1% of male patients, lowered estradiol (14.3% of female patients and lowered insulin-like growth factor I (IGF-I values (12.1% were most common. Using Criterion 2, a higher prevalence rate of 55.6% of cases was determined, which correlated well with the prevalence rate of 54% of cases using the physicians’ diagnosis as the criterion. Intraindividual changes (new onset insufficiency or recovery were predominantly observed for the somatotropic axis (12.5%, the gonadotropic axis in women (11.1% and the corticotropic axis (10.6%. Patients after TBI showed more often lowered IGF-I values at first testing, but normal values at follow-up (p < 0.0004. In general, most patients remained stable. Stable hormone results at follow-up were obtained in 78% (free thyroxine (fT4 values to 94.6% (prolactin values.

  4. Impact of Prenatal Stress on Neuroendocrine Programming

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    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.

  5. Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals.

    Science.gov (United States)

    Bulgari, Dinara; Zhou, Chaoming; Hewes, Randall S; Deitcher, David L; Levitan, Edwin S

    2014-03-04

    Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic basis for presynaptic variation is unknown, past research demonstrated transcriptional control of neuropeptide synthesis suggesting that supply from the soma limits presynaptic neuropeptide accumulation. Here neuropeptide release is shown to scale with presynaptic neuropeptide stores in identified Drosophila cotransmitting and neuroendocrine terminals. However, the dramatic difference in DCV number in these terminals occurs with similar anterograde axonal transport and DCV half-lives. Thus, differences in presynaptic neuropeptide stores are not explained by DCV delivery from the soma or turnover. Instead, greater neuropeptide accumulation in neuroendocrine terminals is promoted by dramatically more efficient presynaptic DCV capture. Greater capture comes with tradeoffs, however, as fewer uncaptured DCVs are available to populate distal boutons and replenish neuropeptide stores following release. Finally, expression of the Dimmed transcription factor in cotransmitting neurons increases presynaptic DCV capture. Therefore, DCV capture in the terminal is genetically controlled and determines neuron-specific variation in peptidergic function.

  6. 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....

  7. 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.

  8. Non-photoperiodic regulation of reproductive physiology in the flexibly breeding pine siskin (Spinus pinus)

    OpenAIRE

    Watts, Heather E.; Hahn, Thomas P.

    2012-01-01

    In order to time reproduction to coincide with favorable conditions, animals use environmental cues to up- and down-regulate the reproductive axis appropriately. Although photoperiodic cues are one of the best studied of such environmental cues, animals also attend to others such as temperature, food availability, rainfall and social cues. Such non-photic cues are expected to be particularly important for tropical species and temperate-zone species that exhibit flexible or opportunistic breed...

  9. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  10. Adaptive Response in Female Fathead Minnows Exposed to an Aromatase Inhibitor: Computational Modeling of the Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  11. A case of insulin and ACTH co-secretion by a neuroendocrine tumour.

    Science.gov (United States)

    Solomou, S; Khan, R; Propper, D; Berney, D; Druce, M

    2014-01-01

    A 33-year-old male was diagnosed with a metastatic neuroendocrine carcinoma of uncertain primary. He defaulted from follow-up without therapy and some months later developed episodic severe hypoglycaemia, which was found to be associated with inappropriately elevated insulin and C-peptide levels. It was considered likely that the neuroendocrine tumour was the source of the insulin secretion. Diazoxide and somatostatin analogue were used to control hypoglycaemia. Much later in the course of the disease, he developed metabolic derangement, increased skin pigmentation and psychological disturbance, without frankly Cushingoid physical findings. Investigations revealed highly elevated cortisol levels (the levels having previously been normal) with markedly raised ACTH levels, consistent with the co-secretion of ACTH and insulin by the tumour. Treatment with metyrapone improved his psychological state and electrolyte imbalance. Unfortunately, despite several cycles of first-, second- and third-line chemotherapy from the start of the first hormonal presentation onwards, imaging revealed widespread progressive metastatic disease and the patient eventually passed away. This case highlights the importance of keeping in mind the biochemical heterogeneity of endocrine tumours during their treatment. The clinical presentation of insulin-secreting tumours includes symptoms of neuroglycopaenia and sympathetic overstimulation.Tumour-associated hypoglycaemia can be due to pancreatic insulinomas, and although ectopic hormone production occurs in a number of tumours, ectopic secretion of insulin is rare.A possible switch in the type of hormone produced can occur during the growth and progression of neuroendocrine tumours and, when treating neuroendocrine tumours, it is important to keep in mind their biochemical heterogeneity.

  12. Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan.

    Science.gov (United States)

    Ito, Tetsuhide; Hijioka, Susumu; Masui, Toshihiko; Kasajima, Atsuko; Nakamoto, Yuji; Kobayashi, Noritoshi; Komoto, Izumi; Hijioka, Masayuki; Lee, Lingaku; Igarashi, Hisato; Jensen, Robert Thomas; Imamura, Masayuki

    2017-01-01

    Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy ( 111 In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.

  13. Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases.

    Science.gov (United States)

    Alejo, Maria; Alemany, Laia; Clavero, Omar; Quiros, Beatriz; Vighi, Susana; Seoud, Muhieddine; Cheng-Yang, Chou; Garland, Suzanne M; Juanpere, Nuria; Lloreta, Josep; Tous, Sara; Klaustermeier, Jo Ellen; Quint, Wim; Bosch, F Xavier; de Sanjosé, Silvia; Lloveras, Belen

    2018-06-01

    Neuroendocrine tumors (NET) of the cervix are rare tumors with a very aggressive course. The human papillomavirus (HPV) has been linked to its etiology. The objective of this study is to describe HPV prevalence and genotype distribution of NET. Forty-nine tumors with histological neuroendocrine features were identified among 10,575 invasive cervical cancer (ICC) cases from an international study. HPV DNA detection was done using SPF10/DEIA /LiPA 25 system. Immunohistochemical (IHC) staining for neuroendocrine markers (chromogranin A, synaptophysin, CD56) and for p16 INK4a as a surrogate for HPV transforming infection was performed. In 13 samples with negative IHC for all 3 neuroendocrine markers studied, it was possible to conduct electron microscopy (EM). NET represented 0.5% of the total ICC series and HPV was detected in 42 out of 49 samples (85.7%, 95%CI:72.8%,94.1%). HPV16 was the predominant type (54.8%), followed by HPV18 (40.5%). p16 INK4a overexpression was observed in 38/44 cases (86.4%). Neuroendocrine IHC markers could be demonstrated in 24/37 (64.9%) cases. EM identified neuroendocrine granules in 8 samples with negative IHC markers. Our data confirms the association of cervical NET with HPV and p16 INK4a overexpression. Specifically, HPV16 and 18 accounted together for over 95% of the HPV positive cases. Current HPV vaccines could largely prevent these aggressive tumors. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

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    Satoshi Takeuchi

    2011-05-01

    Full Text Available High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy.

  15. Interactions between prolactin and kisspeptin to control reproduction.

    Science.gov (United States)

    Donato, Jose; Frazão, Renata

    2016-01-01

    Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin's functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin's actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.

  16. MANAGEMENT OF ENDOCRINE DISEASE: Neuroendocrine surveillance and management of neurosurgical patients.

    Science.gov (United States)

    Garrahy, Aoife; Sherlock, Mark; Thompson, Christopher J

    2017-05-01

    Advances in the management of traumatic brain injury, subarachnoid haemorrhage and intracranial tumours have led to improved survival rates and an increased focus on quality of life of survivors. Endocrine sequelae of the acute brain insult and subsequent neurosurgery, peri-operative fluid administration and/or cranial irradiation are now well described. Unrecognised acute hypopituitarism, particularly ACTH/cortisol deficiency and diabetes insipidus, can be life threatening. Although hypopituitarism may be transient, up to 30% of survivors of TBI have chronic hypopituitarism, which can diminish quality of life and hamper rehabilitation. Patients who survive SAH may also develop hypopituitarism, though it is less common than after TBI. The growth hormone axis is most frequently affected. There is also accumulating evidence that survivors of intracranial malignancy, who have required cranial irradiation, may develop hypopituitarism. The time course of the development of hormone deficits is varied, and predictors of pituitary dysfunction are unreliable. Furthermore, diagnosis of GH and ACTH deficiency require dynamic testing that can be resource intensive. Thus the surveillance and management of neuroendocrine dysfunction in neurosurgical patients poses significant logistic challenges to endocrine services. However, diagnosis and management of pituitary dysfunction can be rewarding. Appropriate hormone replacement can improve quality of life, prevent complications such as muscle atrophy, infection and osteoporosis and improve engagement with physiotherapy and rehabilitation. © 2017 European Society of Endocrinology.

  17. Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

    Directory of Open Access Journals (Sweden)

    Petersenn Stephan

    2006-04-01

    Full Text Available Abstract Background ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. Case presentation A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. Conclusion This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide

  18. Neuroendocrine carcinoma of the mammary gland in a dog.

    Science.gov (United States)

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Change in parent-child conflict and the HPA-axis: Where should we be looking and for how long?

    Science.gov (United States)

    Kuhlman, Kate R.; Repetti, Rena L.; Reynolds, Bridget M.; Robles, Theodore F.

    2017-01-01

    Objective Salivary cortisol is increasingly used as a longitudinal indicator of change in neuroendocrine regulation and as a predictor of health outcomes in youth. The purpose of this study was to describe which indices of HPA-axis functioning are sensitive to changes in parent-child conflict over a three week period and to explore the time course under which these changes can be measured. Methods Youth (n = 47; ages 8–13) completed daily diaries of their conflict with parents for 56 days. On days 17–18 and 38–39, youth contributed saliva samples upon waking, 30-minutes post-waking, afternoon, and bedtime. We assessed change in average diurnal HPA-axis functioning between day 17–18 and day 38–39 as a function of the slopes of change in parent-child conflict over 3 weeks. Results Increasing parent-child conflict was positively associated with concurrent increases in total cortisol output (AUCg), flattening of the diurnal slope, and increases in cortisol at bedtime, but not with change in the cortisol awakening response (CAR). Further, associations between parent-child conflict and both AUCg and bedtime cortisol were observed with at least 14 days of daily diary reporting, whereas any additional ratings of conflict beyond 3 days of daily diaries did not improve model fit for changes in diurnal slope. Conclusions This study demonstrates the within-subject up-regulation of the HPA-axis across three weeks in a healthy sample of youth exposed to natural increases in family conflict. In particular, cortisol at bedtime may be the HPA-axis index that is most sensitive to change over time in parent-child conflict, above and beyond conflict occurring that day. Further, when testing associations between family stressors and diurnal cortisol, the optimal schedule for assessing parent-child conflict varies for different indices of HPA-axis functioning. PMID:26963373

  20. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two cases.

    Science.gov (United States)

    García-Fontán, Eva; Blanco Ramos, Montserrat; García, Jose Soro; Carrasco, Rommel; Cañizares, Miguel Ángel; González Piñeiro, Ana

    2018-05-19

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by a proliferation of neuroendocrine cells within the lung. It is classically described as a disease with persistent cough, dyspnea and wheezing in non-smoker middle aged females. CT of the chest reveals diffuse air trapping with mosaic pattern. We present two cases of DIPNECH that were sent to our department to perform a lung biopsy with the diagnostic suspicion of diffuse interstitial disease. Both cases were women with a history of chronic cough and moderate effort dyspnea. The aim of this paper is that physicians take into account this diagnostic entity before treating as an asthmatic a patient with these characteristics, not forgetting that they are prenoplastic lesions. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  1. Specific targeting for the treatment of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    2003-01-01

    For the treatment of neuroendocrine tumors three ways of specific targeting of radionuclides prevail: by 131 I-meta-iodo-benzyl-guanidine (MIBG), which is taken up by an active uptake-1 mechanism and stored in neurosecretory granules of neural crest tumor cells, by radiolabeled peptides, in particular the somatostatin analogs octreotide and lanreotide, targeting the peptide receptors, and by radiolabeled antibodies, which target tumor cell surface antigens. The choice depends on the indication, the results of diagnostic imaging using tracer amounts of these agents, the availability and feasibility of radionuclide therapy and of other treatment modalities. The applications, clinical results and developments for the major indications are reviewed. 131 I-MIBG therapy has a cumulative response rate of 50%, associated with little toxicity, in metastatic pheochromocytoma, paraganglioma and neuroblastoma, whereas its role is primarily palliative in patients with medullary thyroid carcinoma and carcinoid tumors. Treatment using 90 Y- or 177 Lu-labeled octreotide/lanreotide is mostly used in neuroendocrine gastro-entero-pancreatic (GEP) tumors and paraganglioma, attaining stabilization of disease anti-palliation in the majority of patients. As this treatment is specific for the receptor rather than for the tumor type, it may also be applicable to other, non-neuroendocrine tumors. Radioimmunotherapy is applied in medullary thyroid carcinoma, in which a phase I/II study using bi-specific anti-DTPA/anti-CEA immuno-conjugates followed by 131 I-hapten has proven some degree of success, and may be used in neuroblastoma more effectively than before, once chimeric and humanized monoclonal antibodies become available for therapy. Integration of these specific and noninvasive therapies at an optimal moment into the treatment protocols of these diseases may enhance their effectiveness and acceptance. (author)

  2. Therapy of neuroendocrine carcinoma with Y-90 DOTA- preliminary results

    International Nuclear Information System (INIS)

    Artiko, V.; Obradovic, V.; Nadezda, N.; Djokic, D.; Jankovic, D.; Popovic, B.; Damjanovic, S.; Mikolajczak, R.; Pawlak, D.

    2007-01-01

    Full text: Aim: Cell membrane-specific somatostatin receptors are usually expressed by neuroendocrine tumors. Radiolabelled receptor-binding somatostatin analogues target tissues expressing these receptors and can be used for visualization and treatment. After the localization of tumors bearing somatostatin receptors with 111In or 99mTc labeled somatostatin analogues, in the case of high tumor uptake related to non target tissues, different radioisotopes have been used for their treatment. Thus, application of high doses of 111In- DTPA-octreotide had an impact on improvement of the clinical symptoms, without significant reduction of the tumor mass. However, 90Y somatostatin analogues (DOTA TOC, lanreotide) may be more effective for reduction of the tissue of the larger tumors while 177Lu labeled ones may be applied in smaller tumors. Combination of both of them seems to be the most effective therapy, particularly in tumors bearing both small and large lesions. The aim of this work is presentation of the preliminary results of the therapy of NETs with another octreotide analogue, 90Y DOTA TATE, which so far has been proved to have high therapeutic potential when labeled with 177Lu. Patients and methods: We investigated 7 patients with neuroendocrine tumors (two patients had neuroendocrine pancreatic carcinomas with liver metastases (one of them had metastases in peritoneal lymph nodes), one patient with operated (resected) bronchial carcinoid and liver metastases, three patients with neuroendocrine carcinomas of unknown origin and hepatic metastases (one with skeletal metastases) and one with pancreatic gastrinoma without metastases (surgery was impossible to perform). In all of them, together with other laboratory analyses and imaging methods, scintigraphy with somatostatin analogues was performed (in 3 with 111In Octreoscan and in the other 4 with 99mTc HYNIC TOC) and high tumor uptake was observed. The therapy was performed with 2- 4,5 GBq 90Y DOTA TATE per

  3. The ventral premammillary nucleus links leptin action and reproduction

    Directory of Open Access Journals (Sweden)

    Jose eDonato

    2011-10-01

    Full Text Available The amount of body fat and the energy balance are important factors that influence the timing of puberty and the normal reproductive function. Leptin is a key hormone that conveys to the central nervous system information about the individual energy reserve and modulates the hypothalamus-pituitary-gonad axis. Recent findings suggest that the ventral premammillary nucleus (PMV mediates the effects of leptin as a permissive factor for the onset of puberty and the coordinated secretion of luteinizing hormone during conditions of negative energy balance. Thus, in this review we will summarize the existing literature about the potential role played by PMV neurons in the regulation of the hypothalamus-pituitary-gonad axis.

  4. 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 ...

  5. Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC.

    Science.gov (United States)

    Artiko, Vera; Afgan, Aida; Petrović, Jelena; Radović, Branislava; Petrović, Nebojša; Vlajković, Marina; Šobić-Šaranović, Dragana; Obradović, Vladimir

    2016-01-01

    This paper is the short review of our preliminary results obtained with 99mTc-EDDA/HYNIC-TOC. The total of 495 patients with different neuroendocrine tumors were investigated during last few years. There have been 334 true positive (TP), 73 true negative (TN), 6 false positive (FP) and 82 false negative findings (FN). Diagnosis was made according to SPECT findings in 122 patients (25%). The mean T/NT ratio for TP cases was significantly higher (p < 0.01) on SPECT (3.12 ± 1.13) than on whole body scan (2.2 ± 0.75). According to our results, overall sensitivity of the method is 80%, specificity 92%, positive predictive value 98%, negative predictive value 47% and accuracy 82%. Fifteen TP patients underwent therapy with 90Y-DOTATATE. Scintigraphy of neuroendocrine tumors with 99mTc-Tektrotyd is a useful method for diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors. SPECT had important role in diagnosis. It is also helpful in the appropriate choice of the therapy, including the peptide receptor radionuclide therapy. In the absence of 68Ga-labeled peptides and PET/CT, the special emphasize should be given to application of SPECT/CT as well as to the radioguided surgery.

  6. Advances in the treatment of gastroenteropancreatic neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Pamela L Kunz

    2010-06-01

    Full Text Available Pamela L Kunz, George A FisherStanford University Medical Center, CA, USAAbstract: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs are a rare and heterogeneous class of neoplasms. While surgical resection is the mainstay of treatment, non-surgical therapies play a role in the setting of unresectable and metastatic disease. The goals of medical therapy are directed both at alleviating symptoms of peptide release and shrinking tumor mass. Biotherapies such as somatostatin analogs and interferon can decrease the secretion of peptides and inhibit their end-organ effects. A second objective for treatment of unresectable GEP-NETs is limiting tumor growth. Options for limiting tumor growth include somatostatin analogs, systemic chemotherapy, locoregional therapies, ionizing radiation, external beam radiation, and newer targeted agents. In particular, angiogenesis inhibitors, tyrosine kinase inhibitors, and mTOR inhibitors have shown early promising results. The rarity of these tumors, their resistance to standard chemotherapy, and the excellent performance status of most of these patients, make a strong argument for consideration of novel therapeutic trials.Keywords: neuroendocrine, gastroenteropancreatic, carcinoid, somatostatin

  7. Primary Neuroendocrine Carcinoma of the Breast: Histopathological Criteria, Prognostic Factors, and Review of the Literature

    Science.gov (United States)

    Marinova, Lena; Vicheva, Snezhinka

    2016-01-01

    We present here a case of a 42-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). We discuss the importance of histological criteria for primary neuroendocrine mammary carcinoma, established by WHO in 2003 and 2012. After an overview of different cases of primary neuroendocrine carcinoma of the breast published in the literature, we present information about differential diagnosis, prognostic factors, and surgical and adjuvant treatment. Prognosis of NECB is not different from that of other invasive breast carcinomas and the most important prognostic factor is tumor grade (G). There is no standard treatment and patients should be treated similarly to patients with invasive ductal carcinoma, NOS (not otherwise specified), whose choice of therapy depends on tumor's size, degree of differentiation, clinical stage, and hormonal status. PMID:27840759

  8. Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.

    Science.gov (United States)

    Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

    2016-01-01

    Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment

  9. Pathological characteristics and clinical specifications in gastroenteropancreatic neuroendocrine tumors: a study of 68 cases.

    Science.gov (United States)

    Stoica-Mustafa, Elena; Pechianu, C; Iorgescu, Andreea; Hortopan, Monica; Dima, Simona Olimpia; Tomulescu, V; Dumitraşcu, T; Ungureanu, C; Andronesi, D; Popescu, I; Herlea, V

    2012-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of tumors, having their origin in cells of diffuse endocrine system, with particular clinical course, diagnosis and treatment. In our study, were included 68 patients with neuroendocrine digestive tumors admitted, diagnosed and treated in Fundeni Clinical Institute, Bucharest, in the last ten years--2000-2010 (retrospective study). Thirty-three (49%) patients were males, 35 (51%) females, and the main age was 58.9 years. In 62 (90.3%) cases was possible to find the primary tumor. The examined tumors had different localizations: pancreas--32 (47.04%) cases (head--17 (24.99%) cases, and body and tail--15 (22.05%) cases), stomach--7 (10.29%) cases, small intestine--7 (10.29%) cases, 6 (8.82%) cases--unknown primary site (diagnosis was established on metastases), right colon--6 (8.82%) cases, liver--6 (8.82%) cases, rectum--2 (2.94%) cases, and retroperitoneum--2 (2.94%) cases. Microscopic examination revealed 59 (86.8%) malignant tumors and 9 (13.2%) benign tumors. Using WHO 2000 Classification, 28 cases of malignant tumors were well-differentiated neuroendocrine carcinomas, and 31 cases were poor differentiated neuroendocrine carcinomas. From malignant cases, 25 (42.3%) have distant metastases and 15 (25.9%) lymph node metastases. Cases of gastroenteropancreatic neuroendocrine tumors included in our study had clinical and histopathological features in correspondence with data from literature--slight predominance in women, predominance in 5th and 6th decades of life, the most frequent localizations were at pancreatic level--both head and body and tail, but the rarest were in colon and retroperitoneum. Most of the cases studied, were malignant tumors, from these more than a half were poor differentiated, and a quarter of them having lymph node or distant metastases.

  10. Marijuana, the Endocannabinoid System and the Female Reproductive System

    OpenAIRE

    Brents, Lisa K.

    2016-01-01

    Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormo...

  11. Computational Modeling of Hypothalamic-Pituitary-Gonadal Axis to Predict Adaptive Responses in Female Fathead Minnows Exposed to an Aromatase Inhibitor

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose response and time-course...

  12. Neuroendocrine control in social relationships in non-human primates: Field based evidence.

    Science.gov (United States)

    Ziegler, Toni E; Crockford, Catherine

    2017-05-01

    Primates maintain a variety of social relationships and these can have fitness consequences. Research has established that different types of social relationships are unpinned by different or interacting hormonal systems, for example, the neuropeptide oxytocin influences social bonding, the steroid hormone testosterone influences dominance relationships, and paternal care is characterized by high oxytocin and low testosterone. Although the oxytocinergic system influences social bonding, it can support different types of social bonds in different species, whether pair bonds, parent-offspring bonds or friendships. It seems that selection processes shape social and mating systems and their interactions with neuroendocrine pathways. Within species, there are individual differences in the development of the neuroendocrine system: the social environment individuals are exposed to during ontogeny alters their neuroendocrine and socio-cognitive development, and later, their social interactions as adults. Within individuals, neuroendocrine systems can also have short-term effects, impacting on social interactions, such as those during hunting, intergroup encounters or food sharing, or the likelihood of cooperating, winning or losing. To understand these highly dynamic processes, extending research beyond animals in laboratory settings to wild animals living within their natural social and ecological setting may bring insights that are otherwise unreachable. Field endocrinology with neuropeptides is still emerging. We review the current status of this research, informed by laboratory studies, and identify questions particularly suited to future field studies. We focus on primate social relationships, specifically social bonds (mother-offspring, father-offspring, cooperative breeders, pair bonds and adult platonic friendships), dominance, cooperation and in-group/out-group relationships, and examine evidence with respect to the 'tend and defend' hypothesis. Copyright © 2017

  13. Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

    International Nuclear Information System (INIS)

    Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

    2008-01-01

    To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

  14. CT imaging findings of neuroendocrine tumor arising from tailgut cyst: a case report

    International Nuclear Information System (INIS)

    Aydin, N.; Kara, T.; Kebapci, M.

    2012-01-01

    Full text: Introduction: We present a case of neuroendocrine tumor which is arisen from a tailgut cyst in a middle aged woman with its computed tomography (CT) imaging findings. Objective and tasks:The tailgut normally involutes by the eighth week of gestational age. If a tailgut rest proceeds, it may give rise to a tailgut cyst in the presacral space. Malign transformation of the tailgut cyst is very rare. Material and methods: A 35-year-old woman with a history of endometriosis admitted to our hospital for her routine control.An ultrasonography examination and contrast medium enhanced tomography of the abdomen and pelvis were performed. Results: CT showed multiple well-defined solid heterogen masses in presacral space. The patient underwent surgery. Pathology was reported as neuroendocrine tumor arising within tailgut cyst. Conclusion: Adenocarcinoma, neuroendocrine carcinoma, and sarcoma developing within the tailgut cyst has been reported. CT shows well-marginated presacral mass.If concurrent malignant transformation occurs, CT shows loss of margins and involvement of adjacent structures.Diagnosis of tailgut cyst is important because of it's malignant potential

  15. Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?

    Science.gov (United States)

    Ma, Qiang; Huang, Hui; Sun, Long; Zhou, Tong; Zhu, Jingyuan; Cheng, Xuemin; Duan, Lijv; Li, Zhiyuan; Cui, Liuxin; Ba, Yue

    2017-12-01

    The occurrence of endemic fluorosis is derived from high fluoride levels in drinking water and industrial fumes or dust. Reproductive disruption is also a major harm caused by fluoride exposure besides dental and skeletal lesions. However, few studies focus on the mechanism of fluoride exposure on male reproductive function, especially the possible interaction of fluoride exposure and gene polymorphism on male reproductive hormones. Therefore, we conducted a cross-sectional study in rural areas of Henan province in China to explore the interaction between the estrogen receptor alpha (ERα) gene and fluoride exposure on reproductive hormone levels in male farmers living in the endemic fluorosis villages. The results showed that fluoride exposure significantly increased the serum level of estradiol in the hypothalamic-pituitary-testicular (HPT) axis in male farmers. Moreover, the observations indicated that fluoride exposure and genetic markers had an interaction on serum concentration of follicle-stimulating hormone and estradiol, and the interaction among different loci of the ERα gene could impact the serum testosterone level. Findings in the present work suggest that chronic fluoride exposure in drinking water could modulate the levels of reproductive hormones in males living in endemic fluorosis areas, and the interaction between fluoride exposure and ERα polymorphisms might affect the serum levels of hormones in the HPT axis in male farmers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis

    Directory of Open Access Journals (Sweden)

    Ran Huo

    2017-11-01

    Full Text Available Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA axis under stress. We tested germ-free (GF mice and specific pathogen-free (SPF mice, divided into four groups. A chronic restraint stress (CRS protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.

  17. Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome.

    Science.gov (United States)

    Armario, Antonio

    2010-07-01

    Addictive drugs (opiates, ethanol, cannabinoids (CBs), nicotine, cocaine, amphetamines) induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, with the subsequent release of adrenocorticotropic hormone and glucocorticoids. The sequence of events leading to HPA activation appears to start within the brain, suggesting that activation is not secondary to peripheral homeostatic alterations. The precise neurochemical mechanisms and brain pathways involved are markedly dependent on the particular drug, although it is assumed that information eventually converges into the hypothalamic paraventricular nucleus (PVN). Whereas some drugs may act on the hypothalamus or directly within PVN neurons (i.e. ethanol), others exert their primary action outside the PVN (i.e. CBs, nicotine, cocaine). Corticotropin-releasing hormone (CRH) has a critical role in most cases, but the changes in c-fos and CRH gene expression in the PVN also reveal differences among drugs. More studies are needed to understand how addictive drugs act on this important neuroendocrine system and their functional consequences. Copyright 2010 Elsevier Ltd. All rights reserved.

  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. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Norsk, Peter; Gustafsson, Finn

    2005-01-01

    inhibitors and beta-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady......-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure...

  20. Neuro-endocrine carcinoma of lung

    International Nuclear Information System (INIS)

    Castillo P, Luis Fernando; Restrepo Uribe, Santiago

    1996-01-01

    Review of a case of pathologically proven neuroendocrine tumour of the lung, with clinical and radiological correlation. The case of a young patient is presented that in the first month, it presents two episodes of pneumonitis of the superior lobe from the left lung to the one who after the imagenologic studies and pathological practiced, it was made the diagnose definitive of tumor carcinoid of the lung. Due to the drop incidence in the presentation of this type of tumors in the lung, a revision of the general aspects so much is made clinical as pathological, as well as of the discoveries but important from the imagenologic point of view

  1. Reproductive Late Effects in Female Survivors of Childhood Cancer

    OpenAIRE

    Gnaneswaran, Shivany; Deans, Rebecca; Cohn, Richard J.

    2012-01-01

    Childhood cancer treatments can cause female reproductive late effects. Radiation to the hypothalamic-pituitary-ovarian axis is associated with altered menarche, miscarriage, and implantation failure. Patients who receive chemotherapy and/or ovarian radiation are at risk of premature ovarian failure; the risk increases with increasing radiation dose, alkylating agent score, combination therapy, and older age at treatment. Ovarian reserve may be assessed using antimullerian hormone assay and u...

  2. Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia.

    Science.gov (United States)

    Weber, Matthias M; Fottner, Christian

    2018-01-01

    Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load. © 2018 S. Karger GmbH, Freiburg.

  3. Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

    International Nuclear Information System (INIS)

    Fasshauer, Mathias; Paschke, Ralf; Koch, Christian A; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen

    2006-01-01

    ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111 In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from

  4. Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin

    Directory of Open Access Journals (Sweden)

    Ji Chen

    2018-03-01

    Full Text Available Growth and reproduction are closely related. Growth hormone (GH-transgenic common carp exhibit accelerated growth and delayed reproductive development, which provides an amenable model to study hormone cross talk between the growth and reproductive axes. We analyzed the energy status and reproductive development in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR, Western blotting, ELISA, immunofluorescence, and in vitro incubation. The expression of gys (glycogen synthase and igfbp1 (insulin-like growth factor binding protein as well as blood glucose concentrations are lower in GH-transgenic carp. Agrp1 (agouti-related protein 1 and sla (somatolactin a, which are related to appetite and lipid catabolism, are significantly higher in GH-transgenic carp. Low glucose content and increased appetite indicate disrupted metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the expression of genes, such as gnrhr2 (gonadotropin-releasing hormone receptor 2, gthα (gonadotropin hormone, alpha polypeptide, fshβ (follicle stimulating hormone, beta polypeptide, lhβ [luteinizing hormone, beta polypeptide] in the pituitary, cyp19a1a (aromatase A in the gonad, and cyp19a1b (aromatase B in the hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary gnih (gonadotropin inhibitory hormone, drd1 (dopamine receptor D1, drd3 (dopamine receptor D3, and drd4 (dopamine receptor D4 exhibit increased expression, which were associated with the retarded reproductive development. Leptin receptor mRNA was detected by fluorescence in situ hybridization in the pituitary including the pars intermedia and proximal pars distalis, suggesting a direct effect of leptin on LH. Recombinant carp Leptin protein was shown to stimulate pituitary gthα, fshβ, lhβ expression, and ovarian germinal vesicle breakdown in vitro. In addition to neuroendocrine factors, we suggest that reduced hepatic leptin signaling to the

  5. A Time-course Analysis of Effects of the Steroidogenesis Inhibitor Ketoconazole on Components of the Hypothalamic-pituitary-gonadal Axis of Fathead Minnows

    Science.gov (United States)

    The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

  6. 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors.

    Science.gov (United States)

    Chehab, Farid F

    2014-10-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. © 2014 Society for Endocrinology.

  7. Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Memon, Khairuddin; Lewandowski, Robert J. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Mulcahy, Mary F. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Newman, Steven [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Omary, Reed A. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Benson, Al B. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States)

    2012-07-01

    Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival

  8. [Biotherapy of neuroendocrine tumours of the gastrointestinal tract and pancreas

    DEFF Research Database (Denmark)

    Hansen, C.P.; Knigge, U.

    2008-01-01

    Biotherapy of hormonal symptoms and tumour growth is a mainstay in the therapy of metastatic neuroendocrine tumours of the gastrointestinal tract and pancreas. Symptomatic relief can be achieved by somatostatin analogues and interferon, either alone or in combination. The effect on tumour growth...

  9. Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

    NARCIS (Netherlands)

    Heikens, J.; Michiels, E. M.; Behrendt, H.; Endert, E.; Bakker, P. J.; Fliers, E.

    1998-01-01

    The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25

  10. Neuroendocrine Tumors: A Focus on Liver Metastatic Lesions

    Energy Technology Data Exchange (ETDEWEB)

    Limouris, Georgios S., E-mail: nucleard@aretaieio.uoa.gr [Athens University Medical Faculty, Nuclear Medicine Division, Radiology Department, Aretaieion University Hospital, Athens (Greece)

    2012-02-28

    Transhepatic radionuclide infusion has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan). Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabeled somatostatin analogs, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3 ± 0.3 GBq (∼160–180 mCi) of In-111-DTPA-Phe1-Pentetreotide, 10- to 12-fold in total, administered monthly or of 4.1 ± 0.2 GBq (∼105–116 mCi) of Y-90 DOTA TOC, threefold in total, or of 7.0 ± 0.4 GBq (∼178–200 mCi) of Lu-177 DOTA TATE, fourfold to sixfold in total (the choice of which being based on the tumor size, assessed by CT or MRI). Follow-up at monthly intervals has to be performed by means of ultrasonography (US). Treatment response has to be assessed according to the WHO criteria (RECIST or SWOG).

  11. Neuroendocrine Tumours : From Radiomolecular Imaging to Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    GEORGIOS eLIMOURIS

    2012-02-01

    Full Text Available Transhepatic radionuclide infusion (THRI has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan. Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabelled somatostatin analogues, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3±0.3 GBq (~ 160-180 mCi of In-111-DTPA-Phe1- Pentetreotide, 10-12 fold in total, administered monthly or of 4.1± 0.2 GBq (~105-116 mCi of Y-90 DOTA TOC, 3 fold in total or of 7.0 ± 0.4 GBq (~178-200 mCi of Lu-177 DOTA TATE, 4-6 fold in total (the choice of which being based on the tumor size, assessed by CT or MRI . Follow-up at monthly intervals has to be performed by means of ultrasonography (US. Treat- ment response has to be assessed according to the WHO criteria (RECIST or SWOG.

  12. Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Galleberg, R B; Knigge, U; Tiensuu Janson, E

    2017-01-01

    Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce......., particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.......Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce....... The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended...

  13. [Neuroendocrine immunomodulation].

    Science.gov (United States)

    Uchakin, P N; Uchakina, O N; Tobin, B V; Ershov, F I

    2007-01-01

    Close interaction between the immune and nervous systems is well documented. The ability of immunocompetent cells to express receptors to neuroendocrine mediators as well as secrete many of them is proved. The current literature suggests that the hormones of the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonodal axes play the most significant role in the regulation of immune responsiveness. On the other hand, the immune system communicates with the CNS directly through the cytokines that are able to cross the blood-brain barrier, or directly via the nervus vagus, as well as via secondary messengers. Receptors to a number of cytokines have been found in the nervous tissue. Moreover, glial cells are able to secrete cytokines in the amount significant enough for at least autocrine action. In this article, the authors review the role of the "major" stress hormones such as cortisol, DHEA, growth hormone in the regulation of immune response, as well as neuro- and psychotropic properties of two major groups of cytokines that support cell-mediated (Type 1) and humoral (Type 2) immune reactions. This review emphasizes neuro-endocrine-immune interactions in response to infection both under laboratory and clinical conditions.

  14. Imaging findings of neuroendocrine neoplasm in biliary duct with liver metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Hwa; Chung, Dong Jin; Hahn, Sung Tae; Lee, Jae Moon [Dept. of Radiology, Yeouido St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2013-09-15

    A 64-year-old man was transferred to our hospital because of indigestion and jaundice. The initial abdominal CT and MRI revealed a 2.0 cm enhancing mass in the proximal common bile duct (CBD) with several enlarged lymph nodes. The mass was presumed to be a cholangiocarcinoma, and a CBD segmental resection and choledochojejunostomy was performed. However, the final diagnosis was that of a mixed endocrine-exocrine carcinoma, a high-grade neuroendocrine neoplasm. Seven months after the operation, a follow-up abdominal CT study revealed multiple small arterial enhancing nodules in both hepatic lobes. A sono-guided liver biopsy confirmed these as metastastic mixed endocrine-exocrine carcinoma. This case is unique in that the imaging study regarding the neuroendocrine neoplasm of biliary duct has not been previously reported.

  15. Neuroendocrine tumors: a review of the clinical aspects, diagnosis and treatment

    International Nuclear Information System (INIS)

    Rodriguez Fernandez, Lisbet; Hernandez Yero, Arturo; Pina Rivera, Yordanka; Yanes Quesada, Marelys

    2008-01-01

    The study of neuroendocrine tumors has been object of interests by medical science. Different methods have been developed for their diagnosis, treatment and prognosis, each of them with its advantages and inconveniences. The published results are based on the experience of other countries, and it would be very useful to apply them in our country to get closer to the real incidence of these tumors in our environment and to have an adequate treatment of the patients affected with this disease. The objective of this paper is to offer a view of the current trends as regards the clinical aspects, the diagnosis and treatment of the neuroendocrine tumors that serves as a working tool for medical practice and for the teaching activity of the physicians related to this topic

  16. Duplicating the fine art reproduction process: the technology used for guerilla ink-jet printing

    Science.gov (United States)

    Herron, Stephen

    1998-12-01

    Accurate, automatic color reproduction is the goal of much of color technology. However, there is a need to improve reproduction in only the luminous or gray axis. Quadtone reproduction takes advantage of the four device CMYK color planes to provide greater gray-scale depth within the limitations of 8-bit per channel band-width. 'Quadtone' refers to photos reproduced using four tones of the same colorant. It is the printed imposition of four carefully selected shades of ink that result in a greater number of densities. Guerilla printing is a collection of algorithms using the CMYK channels to simulate traditional photography on an inkjet printer. Guerilla printing increases density values, defines detail and produces near continuous-tone screens.

  17. Review article: the investigation and management of gastric neuroendocrine tumours.

    Science.gov (United States)

    Basuroy, R; Srirajaskanthan, R; Prachalias, A; Quaglia, A; Ramage, J K

    2014-05-01

    Gastric carcinoids (GCs) or neuroendocrine tumours (NETs) are increasingly identified at endoscopy, and account for 0.6-2% of all gastric polyps identified. The SEER database in the US has demonstrated a rising incidence of gastric NETs amongst all NETs; from 2.2% between 1950 and 1969 to 6.0% between 2000 and 2007. To review the literature and assist clinicians in managing patients with GCs. A literature search was conducted through MEDLINE using search terms: gastric, carcinoid, neuroendocrine tumour, therapy, endoscopy, mucosal resection, submucosal dissection. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. There are three types of GCs with important epidemiological, pathophysiological, histological and endoscopic differences that affect prognosis and management. Type 1 and 2 GCs develop in the context of hypergastrinaemia that originates from achlorhydria in atrophic gastritis and a gastrinoma, respectively. Type 3 GCs occur sporadically and independent of gastrin. The histological type, grade and Ki67 index are used to determine prognosis and direct clinical management. Type 1 GCs >1 cm in size and type 2 GCs should be assessed for invasion beyond the submucosa with EUS prior to endoscopic resection with EMR or ESD. Type 3 GCs should be managed as per recommendations for gastric adenocarcinoma. The treatment of advanced disease is multimodal. Patients with gastric carcinoids should be discussed in a specialist neuroendocrine tumour multidisciplinary meeting to ensure all treatment options are explored in localised and advanced disease. Areas of controversy exist that need further research. © 2014 John Wiley & Sons Ltd.

  18. A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

    Science.gov (United States)

    The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

  19. A review of reproductive toxicity of microcystins

    International Nuclear Information System (INIS)

    Chen, Liang; Chen, Jun; Zhang, Xuezhen; Xie, Ping

    2016-01-01

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  20. A review of reproductive toxicity of microcystins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang, E-mail: chan91@yeah.net [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jun, E-mail: chenjun@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhang, Xuezhen, E-mail: xuezhen@mail.hzau.edu.cn [College of Fisheries, Huazhong Agricultural University, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China); Xie, Ping, E-mail: xieping@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

    2016-01-15

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  1. 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.

  2. 18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen

    2014-01-01

    INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...

  3. Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours

    DEFF Research Database (Denmark)

    Yadegarfar, G; Friend, L; Jones, Leigh Robert

    2013-01-01

    Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours.......Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours....

  4. Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle.

    Science.gov (United States)

    Kapoor, Amita; Matthews, Stephen G

    2008-12-01

    Prenatal stress is associated with altered behavior and hypothalamic-pituitary-adrenal (HPA) axis function postnatally. Recent studies suggest that these outcomes are dependent on the timing of the prenatal stress. The majority of these studies have been carried out in male offspring. We hypothesized that a short period of prenatal stress would result in female offspring that exhibit differences in open-field behavior and HPA axis activity, but the outcome would depend on the timing of the prenatal stress and the stage of the reproductive cycle. Pregnant guinea pigs were exposed to a strobe light during the fetal brain growth spurt [gestational d 50-52 (PS50)] or during the period of rapid brain myelination [gestational d 60-62 (PS60)]. Open-field activity was assessed in juvenile and adult female offspring. HPA axis function was tested in adult offspring. All tests in adulthood were carried out during the estrous and luteal phases of the reproductive cycle to determine the effect of stage on HPA axis programming. Tissues were collected upon completion of the study for analysis by in situ hybridization. PS60 offspring exhibited decreased activity in an open field during the estrous phase of the reproductive cycle compared with control offspring. Both PS50 and PS60 offspring exhibited a lower salivary cortisol response to a stressor, only during the estrous phase. Consistent with the behavioral and endocrine data, PS60 females exhibited lower plasma estradiol levels, reduced ovary weight, and increased glucocorticoid receptor mRNA in the paraventricular nucleus. In conclusion, we have demonstrated that there are effects of prenatal stress on behavior and HPA axis functioning in female offspring but that the outcomes are dependent on the timing of the prenatal stress together with the status of the reproductive cycle.

  5. Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

    Science.gov (United States)

    Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

    2018-04-01

    Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

  6. Severe Unresponsive Hypoglycemia Associated with Neuroendocrine Tumor of Unknown Primary Site - 18 Years after Rectal Cancer Surgery. Case Report.

    Science.gov (United States)

    Rusu, Octavia Cristina; Costea, Radu Virgil; Popa, Cristian Constantin; Iliesiu, Andreea; Dumitru, Adrian; Becheanu, Gabriel; Neagu, Stefan Ilie

    2015-09-01

    Neuroendocrine tumors are derived from cells that have the unique ability to synthesize, store and secrete a variety of metabolically active substances, peptides and amines, characteristic of the tissue of origin, which can cause distinct clinical syndromes. We present the case of a 58-year-old patient diagnosed and surgically treated in January 1996 for stage III inferior rectal cancer, who was readmitted after 18 years presenting persistent diarrheic syndrome and asthenia. Investigations performed (abdominal CT) showed multiple liver metastases, initially suspected as being related to the rectal cancer. Biopsy of liver metastases and pathological and immunohistochemical analysis demonstrated the neuroendocrine origin (moderately differentiated neuroendocrine tumor). Seven months after the identification of liver metastases and after initiation of oncological therapy with Interferon and Somatostatin, the patient presented severe hypoglycemia (serum glucose 13-70 mg/dl) proved to be due to insulin-like factors (serum insulin level 64.9 ìU/ml) secreted by metastases. Due to the aggressive evolution of neuroendocrine tumor, with multiple episodes of severe hypoglycemia, resistant to treatment, the patient died approximately one month after the occurrence of hypoglycemic episodes. Despite comprehensive tests (abdominal CT scan, colonoscopy, bone scintigraphy and PET/CT), the primary site of the neuroendocrine tumors remained unknown.

  7. 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.

  8. The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

    Science.gov (United States)

    Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

  9. Effects of aging on the male reproductive system.

    Science.gov (United States)

    Gunes, Sezgin; Hekim, Gulgez Neslihan Taskurt; Arslan, Mehmet Alper; Asci, Ramazan

    2016-04-01

    The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.

  10. Alteration of Neurokinin B Gene Expression and Hypothalamic-Pituitary- Gonadal Axis in Response to One-month Regular Moderate Physical Activity

    Directory of Open Access Journals (Sweden)

    Nazli Khajehnasiri

    2017-08-01

    Full Text Available Abstract Background: The advantageous effects of the regular moderate physical activity (Exercise on reproduction is widely accepted, but until now, the alterations of the expression of hypothalamic arcuate nuclei gene affecting on reproduction axis in response to this type of physical activity are not clear. Therefore, the goal of the present investigation was to study the effect of one –month regular moderate physical activity on neurokinin B gene expression and reproductive axis hormonal changes. Materials and Methods: In the experimental study, fourteen adult male Wistar rats were randomly divided into control and one- month regular moderate exercise groups. After one - month physical activity (20m/min, the arcuate nucleus was isolated from brain and stored in -80 refrigerators for neurokinin B gene expression assay by Real-time PCR method. In addition, serum samples were taken to assess the corticosterone, luteinizing hormone and testosterone levels by ELISA method. Data were analyzed by Independent t-test in SPSS. Results: Neurokinin-B gene expression level was lower in the group which received physical activity than the control group(p<0.05. Also, corticosterone serum concentration was decreased in the physical activity group(p<0.05. By contrast, the physical activity induced luteinizing hormone and Testosterone serum levels evaluation in exersice group compared with control group (p<0.05. Conclusion: Regular moderate physical activity may improve male reproductive performance by reducing the corticosterone hormone level and decreasing neurokinin B expression.

  11. Life-cycle exposure to microcystin-LR interferes with the reproductive endocrine system of male zebrafish.

    Science.gov (United States)

    Su, Yujing; Li, Li; Hou, Jie; Wu, Ning; Lin, Wang; Li, Guangyu

    2016-06-01

    Recently, MC-LR reproductive toxicity drew great attention. Limited information was available on endocrine-disrupting effects of MC-LR on the reproduction system in fish. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L MC-LR for 90 d until they reached sexual maturity. Male zebrafish were selected, and changes in growth and developmental parameters, testicular histological structure as well as the levels of gonadal steroid hormones were studied along with the related-gene transcriptional responses in the hypothalamic-pituitary-gonadal axis (HPG-axis). The results, for the first time, show a life cycle exposure to MC-LR causes growth inhibition, testicular damage and delayed sperm maturation. A significant decrease in T/E2 ratio indicated that MC-LR disrupted sex steroid hormones balance. The changes in transcriptional responses of HPG-axis related genes revealed that MC-LR promoted the conversion of T to E2 in circulating blood. It was also noted that vtg1 mRNA expression in the liver was up-regulated, which implied that MC-LR could induce estrogenic-like effects at environmentally relevant concentrations and long-term exposure. Our findings indicated that a life cycle exposure to MC-LR causes endocrine disruption with organic and functional damage of the testis, which might compromise the quality of life for the survivors and pose a potent threat on fish reproduction and thus population dynamics in MCs-contaminated aquatic environments. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E

    Science.gov (United States)

    Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam

    2011-01-01

    Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094

  13. A time-course analysis of effects of the steroidogenesis inhibitor ketoconazole on components of the hypothalamic-pituitary-gonadal axis of fathead minnows (Presentation)

    Science.gov (United States)

    The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

  14. Focal adhesion kinase, a downstream mediator of Raf-1 signaling, suppresses cellular adhesion, migration, and neuroendocrine markers in BON carcinoid cells.

    Science.gov (United States)

    Ning, Li; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2010-05-01

    We have recently reported that activation of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2)/ERK1/2 signaling cascade in gastrointestinal carcinoid cell line (BON) alters cellular morphology and neuroendocrine phenotype. The mechanisms by which Raf-1 mediates these changes in carcinoid cells are unclear. Here, we report that activation of the Raf-1 signaling cascade in BON cells induced the expression of focal adhesion kinase (FAK) protein, suppressed the production of neuroendocrine markers, and resulted in significant decreases in cellular adhesion and migration. Importantly, inactivation of MEK1/2 by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene or abolition of FAK induction in Raf-1-activated BON cells by targeted siRNA led to reversal of the Raf-1-mediated reduction in neuroendocrine markers and cellular adhesion and migration. Phosphorylation site-specific antibodies detected the phosphorylated FAK(Tyr407), but not FAK(Tyr397), in these Raf-1-activated cells, indicating that FAK(Tyr407) may be associated with changes in the neuroendocrine phenotype. Overexpression of constitutively active FAK plasmids (wild-type FAK or FAK(Tyr397) mutant) into BON cells reduced neuroendocrine markers, whereas the FAK(Tyr407) mutant plasmid did not show any decrease in the levels of neuroendocrine markers, indicating that phosphorylation of FAK at the Tyr(407) residue may be important for these effects. Our results showed for the first time that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade and negatively regulated the neuroendocrine and metastatic phenotype in BON cells. (c)2010 AACR.

  15. Menadione inhibits MIBG uptake in two neuroendocrine cell lines

    NARCIS (Netherlands)

    Cornelissen, J.; Tytgat, G. A.; van den Brug, M.; van Kuilenburg, A. B.; Voûte, P. A.; van Gennip, A. H.

    1997-01-01

    In this paper we report on our studies of the effect of menadione on the uptake of MIBG in the neuroendocrine cell lines PC12 and SK-N-SH. Menadione inhibits the uptake of MIBG in both cell lines in a dose-dependent manner. Inhibition of MIBG uptake is most pronounced in the PC12 cell line.

  16. Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Sabrina C Wentz; Cindy Vnencak-Jones; William V Chopp

    2011-01-01

    Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau casian male to investigate the presence and prognos tic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performedaccording to lab-developed methods, followed by capil lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squa mous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophy sin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar im munohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemo therapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

  17. Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response

    Science.gov (United States)

    New experimental evidence involving the role of neuroendocrine activation challenges an accepted mechanistic paradigm of how irritant air pollutants induce systemic metabolic impairment and lung injury/inflammation. We focus on recent air pollution studies highlighting how the re...

  18. Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, A; Bie, P; Holstein-Rathlou, N H

    2001-01-01

    To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits...... sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P Renal free water clearance increased during WI in control subjects but not in HF......, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast...

  19. Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Wojciech C Blonski; K Rajender Reddy; Abraham Shaked; Evan Siegelman; David C Metz

    2005-01-01

    Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases,alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocinbased chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived.Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver.However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.

  20. Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review

    Institute of Scientific and Technical Information of China (English)

    William; J; Salyers; Kenneth; J; Vega; Juan; Carlos; Munoz; Bruce; W; Trotman; Silvio; S; Tanev

    2014-01-01

    Neuroendocrine tumors(NET)previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome.The annual incidence of patients with NET is 8.4 per 100000;yet many NET remain asymptomatic and clinically undetected.A majority of NET follows a benign course;however,some will display malignant characteristics.NET most commonly occur in the gastrointestinal tract(67%)and bronchopulmonary system(25%).Gastrointestinal NET occur within the stomach,small intestine,liver,and rectum.We report a retrospective study of 11 subjects:Eight with benign carcinoid tumors:duodenal bulb(n=2),terminal ileum(n=1),sigmoid colon(n=2),and rectum(n=3);three with malignant carcinoid:liver(n=1)and intra-abdominal site(n=2).The diagnosis,endoscopic images,outcome,treatment and review of the literature are presented.

  1. RFRP neurons are critical gatekeepers for the photoperiodic control of reproduction

    Directory of Open Access Journals (Sweden)

    Valerie eSimonneaux

    2012-12-01

    Full Text Available Seasonally-breeding mammals rely on the photoperiodic signal to restrict their fertility to a certain time of the year. The photoperiodic information is translated in the brain via the pineal hormone melatonin, and it is now well established that it is the variation in the duration of the nocturnal peak of melatonin which synchronises reproduction with the seasons. The Syrian hamster is a long day breeder, and sexual activity is therefore promoted by exposure to a long day photoperiod and inhibited by exposure to a short day photoperiod. Interestingly, in this species electrolytic lesion of the mediobasal hypothalamus abolishes the short day-induced gonadal regression. We have shown that the expression of a recently discovered neuronal population, namely RFamide-related peptide (rfrp neurons, present in the mediobasal hypothalamus, is strongly down-regulated by melatonin in short day conditions, but not altered by circulating levels of sex steroids. The role of rfrp and its product RFRP-3 in the regulation of reproductive activity has been extensively studied in mammals, and our recent findings indicate that this peptide is a potent stimulator of the reproductive axis in the Syrian hamster. It induces a marked increase in GnRH neuron activity and gonadotrophin secretion, and it is able to rescue reproductive activity in short day sexually inactive hamsters. Little is known about the localisation of the RFRP-3 receptor, GPR147, in the rodent brain. Accumulating evidence suggests that RFRP-3 could be acting via two intermediates, the GnRH neurons in the preoptic area and the Kiss1 neurons in the arcuate nucleus, but future studies should aim at describing the localisation of Gpr147 in the Syrian hamster brain. Altogether our data indicate that the rfrp neuronal population within the mediobasal hypothalamus might be a serious candidate in mediating the photoperiodic effects of melatonin on the regulation of the reproductive axis.

  2. Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function.

    Science.gov (United States)

    Ros-Simó, Clara; Valverde, Olga

    2012-09-01

    Early-life stressful experiences are associated to alterations in behavioural responses and development of psychiatric and neurodegenerative diseases. In rodents, individual housing is considered as a stressful condition whilst enriched environment can protect against stress and its negative consequences. Neuroendocrine responses to stress can also be altered by early-life experiences and seem to contribute to behavioural alterations induced by changes in housing conditions. To develop an improved procedure of social isolation throughout development (from pre-adolescence to adulthood) in CD1 mice and to elucidate its effects on behavioural parameters related to stress and neuroendocrine responses compared to enriched or social conditions. CD1 male mice (PND 21) were housed in social/standard conditions, enriched conditions or isolated conditions during seven weeks. After that, different relevant behaviours were evaluated, including locomotor activity, anxiety-like and despair behaviour. Levels of plasma corticosterone were also analysed before and after a stressful event. CD1 mice exposed to an isolated environment exhibited higher locomotion and anxiety-like responses than animals exposed to social or enriched conditions. In addition, isolated animals showed lower basal plasma corticosterone than social or enriched ones but after a stressful event the elevation of plasma corticosterone was higher, suggesting an enhanced response of the HPA axis to a novel and stressful situation. Social interaction is an important feature to display an appropriate behavioural and neuronal development. Habituation to novel stimuli is impaired in subjects exposed to social isolation and induces increased excitability response to stressful events. Social deprivation increases the possibility of altered neuronal function and could facilitate the development of neuropsychiatric disorders in adulthood. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Metabolic fuel and clinical implications for female reproduction.

    Science.gov (United States)

    Mircea, Carmen N; Lujan, Marla E; Pierson, Roger A

    2007-11-01

    Reproduction is a physiologically costly process that consumes significant amounts of energy. The physiological mechanisms controlling energy balance are closely linked to fertility. This close relationship ensures that pregnancy and lactation occur only in favourable conditions with respect to energy. The primary metabolic cue that modulates reproduction is the availability of oxidizable fuel. An organism's metabolic status is transmitted to the brain through metabolic fuel detectors. There are many of these detectors at both the peripheral (e.g., leptin, insulin, ghrelin) and central (e.g., neuropeptide Y, melanocortin, orexins) levels. When oxidizable fuel is scarce, the detectors function to inhibit the release of gonadotropin-releasing hormone and luteinizing hormone, thereby altering steroidogenesis, reproductive cyclicity, and sexual behaviour. Infertility can also result when resources are abundant but food intake fails to compensate for increased energy demands. Examples of these conditions in women include anorexia nervosa and exercise-induced amenorrhea. Infertility associated with obesity appears to be less related to an effect of oxidizable fuel on the hypothalamic-pituitary-ovarian axis. Impaired insulin sensitivity may play a role in the etiology of these conditions, but their specific etiology remains unresolved. Research into the metabolic regulation of reproductive function has implications for elucidating mechanisms of impaired pubertal development, nutritional amenorrhea, and obesity-related infertility. A better understanding of these etiologies has far-reaching implications for the prevention and management of reproductive dysfunction and its associated comorbidities.

  4. CENTRAL AMYGDALOID INVOLVEMENT IN NEUROENDOCRINE CORRELATES OF CONDITIONED STRESS RESPONSES

    NARCIS (Netherlands)

    ROOZENDAAL, B; KOOLHAAS, JM; BOHUS, B

    The purpose of this study was to examine the effects of bilateral electrolytic lesions of the central nucleus of the amygdala (CEA) in comparison with sham lesions on neuroendocrine responses during conditioned emotional stress in male Wistar rats. Lesions in the CEA, made either before or after the

  5. A study of temporal effects of the model anti-androgen flutamide on components of the hypothalamic-pituitary-gonadal axis in adult fathead minnows

    Science.gov (United States)

    The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal (HPG) axis of fathead minnow (Pimephales promelas) treated with the model androgen receptor (AR) antagonist, flutamide. Reproductively-mature fish were exposed in a flow-through, meas...

  6. Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1

    OpenAIRE

    Tomita, Masaki; Ichiki, Nobuhiko; Ayabe, Takanori; Tanaka, Hiroyuki; Kataoka, Hiroaki; Nakamura, Kunihide

    2017-01-01

    Abstract Thymic epithelial tumors occur in 1?5% of patients with multiple endocrine neoplasia type 1 (MEN 1). Majority of these thymic epithelial tumors are thymic carcinoids and patients with thymoma in MEN 1 is rare. Furthermore, thymoma with neuroendocrine differentiation was also rarely reported. Herein, we report a 68-year-old man having type B3 thymoma with neuroendocrine differentiation in MEN 1 and to the best of our knowledge this is the first such case ever reported.

  7. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Endocrine and Neuroendocrine Neoplasias discusses inherited syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN1, MEN2, MEN4), familial pheochromocytoma and paraganglioma, Carney-Stratakis syndrome, and familial nonmedullary thyroid cancer. Learn more in this clinician summary.

  8. Neuroendocrine-immune interaction: regulation of inflammation via G-protein coupled receptors

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Aa, van der L.M.; Chadzinska, M.K.

    2013-01-01

    Neuroendocrine- and immune systems interact in a bi-directional fashion to communicate the status of pathogen recognition to the brain and the immune response is influenced by physiological changes. The network of ligands and their receptors involved includes cytokines and chemokines,

  9. Neuroendocrine tumor of the appendix inside an incarcerated Amyand’s hernia

    Directory of Open Access Journals (Sweden)

    Khaled Y. Elbanna

    2015-01-01

    An incidental finding of neuroendocrine tumor of the appendix in a patient with s hernia is extremely rare. A high index of suspicion is the key to diagnose such a coincidence in order to safely and optimally treat such a condition.

  10. Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

    Science.gov (United States)

    Kotteas, E A; Pavlidis, N

    2015-04-01

    Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring.

    Science.gov (United States)

    Reynolds, Clare M; Segovia, Stephanie A; Vickers, Mark H

    2017-01-01

    Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

  12. 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

    2015-08-01

    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.

  13. Hsp70 in the atrial neuroendocrine units of the snail, Achatina fulica.

    Science.gov (United States)

    Martynova, M G; Bystrova, O A; Shabelnikov, S V; Margulis, B A; Prokofjeva, D S

    2007-04-01

    Heat shock proteins (Hsps) are evolutionary conserved peptides well known as molecular chaperones and stress proteins. Elevated levels of extracellular Hsps in blood plasma have been observed during the stress responses and some diseases. Information on the cellular sources of extracellular Hsps and mechanisms regulating their release is still scanty. Here we showed the presence and localization of Hsp70 in the neuroendocrine system in the atrium of the snail, Achatina fulica. The occurrence of the peptide in snail atrium lysate was detected by Western blot analysis. Immunoperoxidase and immunogold staining demonstrated that Hsp70-immunoreactivity is mainly confined to the peculiar atrial neuroendocrine units which are formed by nerve fibers tightly contacted with large granular cells. Immunolabelling intensity differed in morphologically distinct types of secretory granules in the granular cells. The pictures of exocytosis of Hsp70-immunolabeled granules from the granular cells were observed. In nerve bundles, axon profiles with Hsp70-immunoreactive and those with non-immunoreactive neurosecretory granules were found. In addition, Hsp70-like material was also revealed in the granules of glia-interstitial cells that accompanied nerve fibers. Our findings provide an immuno-morphological basis for a role of Hsp70 in the functioning of the neuroendocrine system in the snail heart, and show that the atrial granular cells are a probable source of extracellular Hsp70 in the snail hemolymph.

  14. The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects

    Science.gov (United States)

    Pasquali, Renato

    2012-01-01

    Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409

  15. (CT, MRI, USG) radiological diagnostics of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Cwikla, J.; Furmanek, M.; Walecki, J.; Sankowski, A.; Pawlowska-Detko, A.

    2007-01-01

    Neuroendocrine tumors (NET) consists of a heterogeneneous group of neoplasma, that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, which can be used in the localization and treatment of these tumours. Conventionally NETs may present with a wide variety of functional or nonfuctional endocrinesyndromes and may be familial and have other associated tumors, also they have different histology and prognosis. They originate from endocrine glands such as the pituitary, the parathyroids, and the neuroendocrine) adrenal, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as endocrine cells of the digestive system (gastroenteropancreatic GEP-NET0 and respiratory tracts. GEp-NET are the the most common including more 70% of all NETs. Imaging modalities and assessment of specific tumors markers offers high sensitivity in establishing the diagnosis and can also have pronostic significance. One of most important single imaging techniques in terms of initial identification and staging o GET-NET are CT and somatostatin receptor scintigraphy (SRS). Other investigation like magnetic resonance imaging (MRI), endoscopic (EUS) are used for the precise localization of GEP-NET. Another techniques including functional approach 123 I MIBG (meta-iodobenzylguanidine scintigraphy) and FDG PET.Important using of imaging approach is monitoring of response on treatment. (author)

  16. PlanHab study: assessment of psycho-neuroendocrine function in male subjects during 21 d of normobaric hypoxia and bed rest.

    Science.gov (United States)

    Strewe, C; Zeller, R; Feuerecker, M; Hoerl, M; Kumprej, I; Crispin, A; Johannes, B; Debevec, T; Mekjavic, I; Schelling, G; Choukèr, A

    2017-03-01

    Immobilization and hypoxemia are conditions often seen in patients suffering from severe heart insufficiency or primary pulmonary diseases (e.g. fibrosis, emphysema). In future planned long-duration and exploration class space missions (including habitats on the moon and Mars), healthy individuals will encounter such a combination of reduced physical activity and oxygen tension by way of technical reasons and the reduced gravitational forces. These overall unconventional extraterrestrial conditions can result in yet unknown consequences for the regulation of stress-permissive, psycho-neuroendocrine responses, which warrant appropriate measures in order to mitigate foreseeable risks. The Planetary Habitat Simulation Study (PlanHab) investigated these two space-related conditions: bed rest as model of reduced gravity and normobaric hypoxia, with the aim of examining their influence on psycho-neuroendocrine responses. We hypothesized that both conditions independently increase measures of psychological stress and enhance neuroendocrine markers of stress, and that these effects would be exacerbated by combined treatment. The cross-over study composed of three interventions (NBR, normobaric normoxic horizontal bed rest; HBR, normobaric hypoxic horizontal bed rest; HAMB, normobaric hypoxic ambulatory confinement) with 14 male subjects during three sequential campaigns separated by 4 months. The psychological state was determined through three questionnaires and principal neuroendocrine responses were evaluated by measuring cortisol in saliva, catecholamine in urine, and endocannabinoids in blood. The results revealed no effects after 3 weeks of normobaric hypoxia on psycho-neuroendocrine responses. Conversely, bed rest induced neuroendocrine alterations that were not influenced by hypoxia.

  17. [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.

  18. Therapy evaluation and diagnostic accuracy in neuroendocrine tumours: assessment of radiological methods

    International Nuclear Information System (INIS)

    Elvin, A.

    1993-01-01

    The diagnostic accuracy of ultrasonically guided biopsy-gun biopsies was assessed in a group of 47 patients with suspected pancreatic carcinoma. A correct diagnosis was obtained in 44 of the 47 patients (94%). Biopsy-gun biopsy of the pancreas is considered a useful, reliable and non-traumatic method for the diagnosis of pancreatic malignancy. Twenty-five patients with known neuroendocrine tumour disease were biopsied with 1.2 mm and 0.9 mm biopsy-gun needles. The influence of treatment-related fibrosis was also evaluated. The overall diagnostic accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm needle. In order to assess the diagnostic accuracy rate for radiologists with different experience of biopsy procedures 175 cases of renal biopsy-gun biopsies were evaluated. No statistical significant difference was found between the different operators. The role of duplex Doppler ultrasound in monitoring interferon treatment-related changes in carcinoid metastases was evaluated. It present duplex Doppler ultrasound does not seem to play a role in the evaluation of tumour therapy in carcinoid patients. Therapy response evaluation was performed with MR imaging in a group of 17 patients with neuroendocrine liver metastases. A significant difference was found between patients responding to and patients with failure of treatment in terms of tumour T1, contrast enhancement and signal intensity ratio. This indicates that MR investigation may be used in therapy monitoring of patients with neuroendocrine metastases. The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 mice to establish a tumour/animal model that would allow the monitoring of changes with MR imaging induced by interferon therapy and to evaluate whether the therapeutic response could be modulated by different interferon dosages. Interferon does not seem to have any prolonged anti-proliferative effect on the LCC-18 tumour cell line when transplanted to

  19. Stress and the Adolescent Brain: Plasticity of Reproductive Behaviors in Female

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    Farideh Zafari Zangeneh

    2009-03-01

    Full Text Available Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging.  Much research attention has focused on the programming effects of the hypothalamus pituitary axis (HPA in early life and on understanding HPA function in response to stressors in adulthood. In comparison, there has been relatively little research on adolescence, a time of significant brain development particularly in the frontal lobe and a time which is of great importance for mental and physical health. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. During adolescence, HPA function is characterized by a prolonged activation in response to stressors compared to adulthood, which may render ongoing development of the brain vulnerable. Stress reactivity is markedly influenced by both the pubertal maturation and the experience of the individual. The frequency of the pulses is increased in chronic stress, since the neuroendocrine system is such a good candidate for mediators of many diseases linked to chronic stress. The activity of HPA axis  in life time of female,  sex maturity, pregnancy or lactation is a plasticity of the diurnal rhythm of pulse amplitude; chronic stress can change this program for   formation disorder in behavioral and physiological responses.

  20. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry.

    Science.gov (United States)

    Hörsch, Dieter; Ezziddin, Samer; Haug, Alexander; Gratz, Klaus Friedrich; Dunkelmann, Simone; Krause, Bernd Joachim; Schümichen, Carl; Bengel, Frank M; Knapp, Wolfram H; Bartenstein, Peter; Biersack, Hans-Jürgen; Plöckinger, Ursula; Schwartz-Fuchs, Sabine; Baum, R P

    2013-01-01

    Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.

  1. Neuroendocrine tumors of the pancreas

    International Nuclear Information System (INIS)

    Holzapfel, Konstantin; Rummeny, Ernst J.; Gaertner, Florian C.

    2011-01-01

    Neuroendocrine tumors (NET) of the pancreas are rare entities. Functioning tumors tend to present early with specific symptoms and typical abnormalities in laboratory values. In contrast, non-functioning NET are often diagnosed with delay and become evident by tumor-related symptoms like pain, weight-loss or jaundice. The role of imaging is to localize and delineate the primary tumor and to detect metastases. In the diagnosis of NET radiologic techniques like computed tomography (CT) and magnetic resonance imaging (MRI) are applied. In certain cases nuclear medicine techniques like somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using radioactively labelled somatostatin analogues are used. The present article reviews characteristic imaging findings of both functioning and non-functioning NET of the pancreas. (orig.)

  2. Metabolic and endocrine profiles and reproductive parameters in dairy cows under grazing conditions: effect of polymorphisms in somatotropic axis genes

    Directory of Open Access Journals (Sweden)

    Pereira Isabel

    2011-06-01

    Full Text Available Abstract Background The present study hypothesized that GH-AluI and IGF-I-SnabI polymorphisms do change the metabolic/endocrine profiles in Holstein cows during the transition period, which in turn are associated with productive and reproductive parameters. Methods Holstein cows (Farm 1, primiparous cows, n = 110, and Farm 2, multiparous cows, n = 76 under grazing conditions were selected and GH and IGF-I genotypes were determined. Blood samples for metabolic/endocrine determinations were taken during the transition period and early lactation in both farms. Data was analyzed by farm using a repeated measures analyses including GH and IGF-I genotypes, days and interactions as fixed effects, sire and cow as random effects and calving date as covariate. Results and Discussion Frequencies of GH and IGF-I alleles were L:0.84, V:0.16 and A:0.60, B:0.40, respectively. The GH genotype was not associated with productive or reproductive variables, but interaction with days affected FCM yield in multiparous (farm 2 cows (LL yielded more than LV cows in early lactation. The GH genotype affected NEFA and IGF-I concentrations in farm 1 (LV had higher NEFA and lower IGF-I than LL cows suggesting a better energy status of LL cows. There was no effect of IGF-I genotype on productive variables, but a trend was found for FCM in farm 2 (AB cows yielded more than AA cows. IGF-I genotype affected calving first service interval in farm 1, and the interaction with days tended to affect FCM yield (AB cows had a shorter interval and yielded more FCM than BB cows. IGF-I genotype affected BHB, NEFA, and insulin concentrations in farm 1: primiparous BB cows had lower NEFA and BHB and higher insulin concentrations. In farm 2, there was no effect of IGF-I genotype, but there was an interaction with days on IGF-I concentration, suggesting a greater uncoupling somatropic axis in AB and BB than AA cows, being in accordance with greater FCM yield in AB cows. Conclusion The GH and

  3. Metabolic and endocrine profiles and reproductive parameters in dairy cows under grazing conditions: effect of polymorphisms in somatotropic axis genes

    Science.gov (United States)

    2011-01-01

    Background The present study hypothesized that GH-AluI and IGF-I-SnabI polymorphisms do change the metabolic/endocrine profiles in Holstein cows during the transition period, which in turn are associated with productive and reproductive parameters. Methods Holstein cows (Farm 1, primiparous cows, n = 110, and Farm 2, multiparous cows, n = 76) under grazing conditions were selected and GH and IGF-I genotypes were determined. Blood samples for metabolic/endocrine determinations were taken during the transition period and early lactation in both farms. Data was analyzed by farm using a repeated measures analyses including GH and IGF-I genotypes, days and interactions as fixed effects, sire and cow as random effects and calving date as covariate. Results and Discussion Frequencies of GH and IGF-I alleles were L:0.84, V:0.16 and A:0.60, B:0.40, respectively. The GH genotype was not associated with productive or reproductive variables, but interaction with days affected FCM yield in multiparous (farm 2) cows (LL yielded more than LV cows) in early lactation. The GH genotype affected NEFA and IGF-I concentrations in farm 1 (LV had higher NEFA and lower IGF-I than LL cows) suggesting a better energy status of LL cows. There was no effect of IGF-I genotype on productive variables, but a trend was found for FCM in farm 2 (AB cows yielded more than AA cows). IGF-I genotype affected calving first service interval in farm 1, and the interaction with days tended to affect FCM yield (AB cows had a shorter interval and yielded more FCM than BB cows). IGF-I genotype affected BHB, NEFA, and insulin concentrations in farm 1: primiparous BB cows had lower NEFA and BHB and higher insulin concentrations. In farm 2, there was no effect of IGF-I genotype, but there was an interaction with days on IGF-I concentration, suggesting a greater uncoupling somatropic axis in AB and BB than AA cows, being in accordance with greater FCM yield in AB cows. Conclusion The GH and IGF-I genotypes had no

  4. The relationship between intraspecific assortative mating and reproductive isolation between divergent populations

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    Daniel I. BOLNICK, Mark KIRKPATRICK

    2012-06-01

    Full Text Available The term 'assortative mating' has been applied to describe two very different phenomena: (1 the tendency for individuals to choose phenotypically similar mates from among conspecifics; or (2 the tendency to prefer conspecific over hete- rospecific mates (behavioral reproductive isolation. Both forms of assortative mating are widespread in nature, but the relationship between these behaviors remains unclear. Namely, it is plausible that a preference for phenotypically similar conspecifics incidentally reduces the probability of mating with phenotypically divergent heterospecifics. We present a model to calculate how the level of reproductive isolation depends on intraspecific assortative mating and the phenotypic divergence between species. For empirically reasonable levels of intraspecific assortment on a single trait axis, we show that strong reproductive isolation requires very substantial phenotypic divergence. We illustrate this point by applying our model to empirical data from threespine stickleback Gasterosteus aculeatus and Darwin’s Finches (Geospiza spp. We conclude that typical levels of intraspecific assortment cannot generally be extrapolated to explain levels of interspecific reproductive isolation. Instead, reproductive isolation between species likely arises from different mate choice behaviors, or multivariate assortative mating [Current Zoology 58 (3: 481–489, 2012].

  5. Child Maltreatment and Gender Interactions as Predictors of Differential Neuroendocrine Profiles

    Science.gov (United States)

    Doom, Jenalee R.; Cicchetti, Dante; Rogosch, Fred A.; Dackis, Melissa N.

    2013-01-01

    Summary Child maltreatment is a potent stressor associated with neuroendocrine dysregulation and increased risk for mental and physical disorders throughout the lifespan. Gender differences in stress reactivity and adult psychopathology prevalence may be related to sex-specific responsivity to stress. The purpose of this study is to examine whether gender interacts with the stress of maltreatment to produce differential neuroendocrine profiles in children. Participants included 137 maltreated and 110 nonmaltreated low-income, racially and ethnically diverse children (range: 7.9–10.9 years; M= 9.42 years; 52% male) who attended a summer research day camp. Saliva was collected 3 times across the day for 5 days for cortisol and dehydroepiandosterone (DHEA) analysis. Department of Human Services records were examined to determine the type, severity, chronicity, onset, and recency of maltreatment for children in the maltreated group. Significant interactions between gender and maltreatment pervasiveness predicted diurnal cortisol, DHEA, and cortisol/DHEA ratio levels. Elevated daily cortisol levels were reported for boys compared to girls in the group with more pervasive maltreatment. Boys with less pervasive maltreatment had lower DHEA and higher cortisol/DHEA ratio levels than girls with similar experiences, nonmaltreated boys, and boys with more pervasive maltreatment. Further results are consistent with down-regulation of cortisol production in girls with more pervasive maltreatment and girls who experienced maltreatment that was early onset and not recent. The effectiveness of interventions for maltreated children may be improved with greater knowledge of how maltreatment differentially affects neuroendocrine regulation by gender. PMID:23333253

  6. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

    Science.gov (United States)

    Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

    2018-04-15

    Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

  7. Goldfish neurokinin B: Cloning, tissue distribution, and potential role in regulating reproduction.

    Science.gov (United States)

    Qi, Xin; Zhou, Wenyi; Li, Shuisheng; Liu, Yun; Ye, Gang; Liu, Xiaochun; Peng, Chun; Zhang, Yong; Lin, Haoran

    2015-09-15

    Neurokinin B (NKB) is a member of the tackykinin (TAC) family known to play a critical role in the neuroendocrine regulation of reproduction in mammals. However, its biological functions in teleosts are less clear. The aim of this study was to determine the role of NKB in fish reproduction using goldfish as a model. Two transcripts, TAC3a and TAC3b, which encode several NKBs, including NKBa-13, NKBa-10, NKBb-13, and NKBb-11, were cloned. Phylogenetic analysis revealed that NKBa-10 and NKBb-11 are closely related to mammalian NKB, while NKB-13s are more conserved in teleosts. Quantitative real-time PCR analyses in various tissues showed that TAC3a and TAC3b mRNAs were mainly expressed in the brain. In situ hybridization further detected TAC3a and TAC3b mRNAs in several regions of the brain known to be involved in the regulation of reproduction and metabolism, as well as in the neurohypophysis of the pituitary. To investigate the potential role of NKBs in reproduction, goldfish were injected intraperitoneally with synthetic NKBa-13, -10, NKBb-13, or -11 peptides and the mRNA levels of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin subunits were measured. NKBa-13, -10, or NKBb-13, but not -11, significantly increased hypothalamic salmon GnRH and pituitary FSHβ and LHβ mRNA levels in both female and male goldfish. Finally, ovariectomy increased, while estradiol replacement reduced, TAC3a mRNA levels without affecting TAC3b expression in the hypothalamus. These data suggest that NKBa-13, -10, and NKBb-13 play a role in mediating the estrogen negative feedback regulation of gonadotropins. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor of the urinary bladder: case report

    Directory of Open Access Journals (Sweden)

    De Rosa Gaetano

    2005-07-01

    Full Text Available Abstract Background The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. Case presentation The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. Conclusion This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms.

  9. Stress and fish reproduction: The roles of allostasis and hormesis

    Science.gov (United States)

    Schreck, C.B.

    2010-01-01

    This paper is a review of the effects of stress on reproduction in fishes. I hope to further the development of the concepts of allostasis and hormesis as relevant to understanding reproduction in general and in fish in particular. The main contentions I derive in this review are the following: Stressors affect fish reproduction in a variety of ways depending on the nature and severity of the stressor. The effects are transduced through a hormonal cascade initiated by perception of the stressor and involving the hypothalamus-pituitary-interrenal axis, the catecholamines, and also cytokines. Mounting a stress response and resisting a stressor is an energetically costly process, including costs associated with allostasis, attempting to reset homeostatic norms. Responses in emergency situations (e.g., being chased by a predator or a net) can be different from those where fish can cope (e.g., being in a more crowded environment) with a stressor, but both situations involve energy re-budgeting. Emergency responses happen in concert with the onset of energy limitations (e.g., the fish may not eat), while coping with allostatic overload can happen in a more energy-rich environment (e.g., the fish can continue to eat). Low levels of stress may have a positive effect on reproductive processes while greater stress has negative effects on fish reproduction. The concept of hormesis is a useful way to think about the effect of stressors on fish reproduction since responses can be nonmonotonal, often biphasic.

  10. Nuclear medicine technology for diagnosisof neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    D. V. Ryzhkova

    2013-01-01

    Full Text Available This article is the review of issues of the literature for the past 10 years and is dedicated to the analysis of the radiopharmaceuticals and efficacy of the novel nuclear medicine technologies for the diagnosis, staging and prognosis of neuroendocrine tumors. Diagnostic efficacy of a scintigraphy and a positron emission tomography for detection of gastroenteropancreatic and lung carcinoid, medullary thyroid cancer, pheochromocytoma and haraganglioma and choice of radiopharmaceuticals were demonstrated by the results of the clinical studies. The causes of false positive and falce negative results were specified.

  11. Evaluating reproductive decisions as discrete choices under social influence.

    Science.gov (United States)

    Bentley, R Alexander; Brock, William A; Caiado, Camila C S; O'Brien, Michael J

    2016-04-19

    Discrete choice, coupled with social influence, plays a significant role in evolutionary studies of human fertility, as investigators explore how and why reproductive decisions are made. We have previously proposed that the relative magnitude of social influence can be compared against the transparency of pay-off, also known as the transparency of a decision, through a heuristic diagram that maps decision-making along two axes. The horizontal axis represents the degree to which an agent makes a decision individually versus one that is socially influenced, and the vertical axis represents the degree to which there is transparency in the pay-offs and risks associated with the decision the agent makes. Having previously parametrized the functions that underlie the diagram, we detail here how our estimation methods can be applied to real-world datasets concerning sexual health and contraception. © 2016 The Author(s).

  12. Infertility in reproductive-age female cancer survivors.

    Science.gov (United States)

    Levine, Jennifer M; Kelvin, Joanne Frankel; Quinn, Gwendolyn P; Gracia, Clarisa R

    2015-05-15

    Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program. © 2015 American Cancer Society.

  13. Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

    Directory of Open Access Journals (Sweden)

    Julia Lipianskaya

    2014-08-01

    Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

  14. Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides.

    Science.gov (United States)

    Marvel, Miranda; Spicer, Olivia Smith; Wong, Ten-Tsao; Zmora, Nilli; Zohar, Yonathan

    2018-04-04

    Gonadotropin-releasing hormone (GnRH) is known as a pivotal upstream regulator of reproduction in vertebrates. However, reproduction is not compromised in the hypophysiotropic Gnrh3 knockout line in zebrafish (gnrh3-/-). In order to determine if Gnrh2, the only other Gnrh isoform in zebrafish brains, is compensating for the loss of Gnrh3, we generated a double Gnrh knockout zebrafish line. Surprisingly, the loss of both Gnrh isoforms resulted in no major impact on reproduction, indicating that a compensatory response, outside of the Gnrh system, was evoked. A plethora of factors acting along the reproductive hypothalamus-pituitary axis were evaluated as possible compensators based on neuroanatomical and differential gene expression studies. In addition, we also examined the involvement of feeding factors in the brain as potential compensators for Gnrh2, which has known anorexigenic effects. We found that the double knockout fish exhibited upregulation of several genes in the brain, specifically gonadotropin-inhibitory hormone (gnih), secretogranin 2 (scg2), tachykinin 3a (tac3a), and pituitary adenylate cyclase-activating peptide 1 (pacap1), and downregulation of agouti-related peptide 1 (agrp1), indicating the compensation occurs outside of Gnrh cells and therefore is a non-cell autonomous response to the loss of Gnrh. While the differential expression of gnih and agrp1 in the double knockout line was confined to the periventricular nucleus and hypothalamus, respectively, the upregulation of scg2 corresponded with a broader neuronal redistribution in the lateral hypothalamus and hindbrain. In conclusion, our results demonstrate the existence of a redundant reproductive regulatory system that comes into play when Gnrh2 and Gnrh3 are lost.

  15. The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2017-10-01

    Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second...... neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after...... every three courses. Hematological toxicity was assessed by CTC-criteria. RESULTS: Twenty-two eligible patients received a median of 2 courses [range1-6]. Median age: 65 years [35-77]. Male/female: 11/11. Median Ki-67 index: 95% [25-100%]. Median number previous chemotherapy regimens: 2 [1-3]. All...

  17. Poorly differentiated neuroendocrine carcinoma of the pancreas responsive to combination therapy with gemcitabine and S-1.

    Science.gov (United States)

    Yamamoto, Mitsuyoshi; Miyagawa, Koichiro; Hiura, Masaaki; Taguchi, Masashi; Kihara, Yasuyuki; Abe, Shintaro; Shimajiri, Shohei; Harada, Masaru

    2012-01-01

    Poorly differentiated neuroendocrine carcinoma is a very rare malignancy, but it is characterized by agressive histological features and a poor clinical prognosis. We report a 42-year-old man who had poorly differentiated neuroendocrine carcinoma of the pancreas with multiple liver metastases. We administrated combined chemotherapy with S-1 and gemcitabine. This treatment was efficacious and well tolerated, and then this patient obtained objective partial response for 7 months and survived for 13 months after the diagnosis. This case suggests that S-1 and gemcitabine combination produce beneficial responses for patients with this disease.

  18. Microbial endocrinology and the microbiota-gut-brain axis.

    Science.gov (United States)

    Lyte, Mark

    2014-01-01

    Microbial endocrinology is defined as the study of the ability of microorganisms to both produce and recognize neurochemicals that originate either within the microorganisms themselves or within the host they inhabit. As such, microbial endocrinology represents the intersection of the fields of microbiology and neurobiology. The acquisition of neurochemical-based cell-to-cell signaling mechanisms in eukaryotic organisms is believed to have been acquired due to late horizontal gene transfer from prokaryotic microorganisms. When considered in the context of the microbiota's ability to influence host behavior, microbial endocrinology with its theoretical basis rooted in shared neuroendocrine signaling mechanisms provides for testable experiments with which to understand the role of the microbiota in host behavior and as importantly the ability of the host to influence the microbiota through neuroendocrine-based mechanisms.

  19. Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

    Science.gov (United States)

    Shen, Chaoyong; Yin, Yuan; Chen, Huijiao; Tang, Sumin; Yin, Xiaonan; Zhou, Zongguang; Zhang, Bo; Chen, Zhixin

    2017-03-28

    This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

  20. Neuroendocrine carcinomas of the lung

    International Nuclear Information System (INIS)

    Forster, B.B.; Muller, N.L.; Miller, R.R.; Nelems, B.; Evans, K.G.

    1988-01-01

    Neuroendocrine lung carcinomas may be classified as Kulchitzky cell carcinoma (KCC) I (classic carcinoids), II (atypical carcinoids), and III (small cell carcinomas). The authors reviewed the clinical, CT, and pathologic findings in 31 patients with KCC. KCC I occurred mainly in younger nonsmoking women, and on CT were small (1.8 cm average diameter) and showed lymphadenopathy in one of ten patients. KCC II were found mainly in older smoking men and were larger (3.9 cm, P < .001), and four of ten patients had lymphadenopathy. KCC III occurred in older smoking men and were large (4.2 cm), and 11 of 11 patients had lymphadenopathy. Sputum cytology and percutaneous and bronchoscopic biopsy were often nondiagnostic or misleading. The authors conclude that chest CT provides additional discriminating information in the preoperative diagnosis of KCC

  1. 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.

  2. Neuroendocrine tumors of the gallbladder: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Mezi Silvia

    2011-07-01

    Full Text Available Abstract Introduction Primary gallbladder neuroendocrine tumors are extremely rare, representing 0.2% of all neuroendocrine tumors. The diagnosis is incidental in most cases. Case presentation We describe the case of a 57-year-old Caucasian man who underwent laparoscopic cholecystectomy for the evaluation of a gallbladder polyp that had been incidentally detected by ultasonography. Histologically, his lesion was composed of monomorphic cells that contained small round nuclei and that were organized in small nodular, trabecular, and acinar structures. His cells were positive for chromogranin A and synaptophysin, and a diagnosis of "typical" carcinoid of the gallbladder was made. His post-operative computerized axial tomography, 111In-pentetreotide scintigraphy, and hormone-specific marker results were negative. He is disease-free 45 months after surgical treatment. Conclusions Characteristic pathological findings of the gallbladder neuroendocrine tumors predict the prognosis. Whereas classical carcinoids of the gallbladder only rarely have a metastatic or invasive phenotype, the "atypical" variants are more aggressive and are associated with a poorer prognosis. Given the difficulty in distinguishing between benign and malignant lesions in the pre-surgical setting, we tend to consider each polypoid-like lesion of the gallbladder to be a high-risk lesion if it is larger than 1 cm and, as a result, to emphasize the need for cholecystectomy in all cases, relying on the pathological and immunohistochemistry analyses for the final diagnosis.

  3. Neuroendocrine tumour of the cervix: A case report and review of ...

    African Journals Online (AJOL)

    Cervical neuroendocrine tumours are rare accounting for only 2% of cervical cancers. They pose a management challenge. We present a case of a 26-year old who presented with bleeding pervaginum three months post partum and a cervical mass on speculum examinations. Further examination and histology revealed an ...

  4. Neuroendocrine and cardiovascular reactions to acute psychological stress are attenuated in smokers

    NARCIS (Netherlands)

    Ginty, Annie T.; Jones, Alexander; Carroll, Douglas; Roseboom, Tessa J.; Phillips, Anna C.; Painter, Rebecca; de Rooij, Susanne R.

    2014-01-01

    A number of studies have now examined the association between smoking and the magnitude of physiological reactions to acute psychological stress. However, no large-scale study has demonstrated this association incorporating neuroendocrine in addition to cardiovascular reactions to stress. The

  5. Reproductive hormone levels in men exposed to persistent organohalogen pollutants: a study of inuit and three European cohorts

    DEFF Research Database (Denmark)

    Giwercman, Aleksander; Rignell-Hydbom, Anna; Toft, Gunnar

    2006-01-01

    OBJECTIVE: Persistent organohalogen pollutant (POP) exposure may have a negative impact on reproductive function. The objective of this study was to assess the impact of POP exposure on the male hypothalamo-pituitary-gonadal axis. PARTICIPANTS: Participants included 184 Swedish fishermen and spou...

  6. Behavioural and Neuroendocrine Effects of Stress in Salmonid Fish

    OpenAIRE

    Øverli, Øyvind

    2001-01-01

    Stress can affect several behavioural patterns, such as food intake and the general activity level of an animal. The central monoamine neurotransmitters serotonin, dopamine, and norepinephrine are important in the mediation of both behavioural and neuroendocrine stress effects. This thesis describes studies of two salmonid fish model systems: Fish that become socially dominant or subordinate when reared in pairs, and rainbow trout (Oncorhynchus mykiss) genetically selected for high (HR) and l...

  7. Evaluating obesity in fibromyalgia: neuroendocrine biomarkers, symptoms, and functions

    OpenAIRE

    Okifuji, Akiko; Bradshaw, David H.; Olson, Chrisana

    2009-01-01

    The aim of this study was to investigate the associations between obesity and fibromyalgia syndrome (FMS). This study was conducted at the University of Utah Pain Management and Research Center, Salt Lake City, Utah. Thirty-eight FMS patients were included in this study. Neuroendocrine indices (catecholamines, cortisol, C-reactive protein [CRP], and interleukin-6), symptom measures (Fibromyalgia Impact Questionnaire), sleep indices (Actigraph), and physical functioning (treadmill testing) wer...

  8. Diagnosis and Management of Upper Gastrointestinal Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Jun Liong Chin

    2017-11-01

    Full Text Available Upper gastrointestinal neuroendocrine tumors (NETs are rare tumors which are increasingly recognised by practising endoscopists. After confirmation by endoscopic biopsies of these focal lesions, many questions may arise. As NETs are less frequently encountered compared to other malignancies or gastrointestinal pathology, many endoscopists may not fully understand the natural history, diagnosis and management of these tumors. In this review, we aim to update the practising endoscopist on the key clinical features and management of patients with upper gastrointestinal NET.

  9. Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of 240 breast cancer patients

    DEFF Research Database (Denmark)

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

    2014-01-01

    Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not recognized by WHO until 2003 - has lately been the subject of increasing attention. It is defined as a primary breast cancer with morphologic features similar to other types of neuroendocrine tumors of the lung......, apparent limitations of the WHO definition appear to influence diagnosis. Here, we present our own results obtained from 13 cases and furthermore review previous reports with particular reference to incidence, clinical, histological, and prognostic features....

  10. Electroconvulsive therapy's mechanism of action: neuroendocrine hypotheses.

    Science.gov (United States)

    Haskett, Roger F

    2014-06-01

    Despite a range of etiological theories since the introduction of electroconvulsive therapy (ECT) more than 75 years ago, its mechanism of action remains poorly understood. The neuroendocrine hypothesis is based on the seizure-related release of hypothalamic hormones into the blood and cerebrospinal fluid and evidence of endocrine dysfunction in many patients with severe mood disorder. The specific effect of ECT was hypothesized to result from the transverse passage of current through the brain with direct stimulation of axial structures including the diencephalon. The prompt release of adrenocorticotropic hormone, cortisol, and prolactin into blood followed ECT with a return to pretreatment baseline levels in several hours. The elevated levels of hormones were absorbed by the cerebrospinal fluid, providing contact with brain cells and central nervous system structures. An apparently specific pattern of ECT-induced hormone changes, limited to prolactin and cortisol, suggested that ECT released a substance with dopaminergic antagonist and antipsychotic properties. As hypothalamic dysfunction is a key finding in endogenomorphic depression and the abnormal endocrine and physiological functions usually normalize with recovery, this led to a search for biological markers that would supplement clinical assessment of diagnosis and treatment response. One of these, the overnight dexamethasone suppression test found that 40% to 50% of melancholic depressed patients had abnormal results, whereas 90% of control patients suppressed normally. This was followed by a period of uncritical overenthusiasm followed by wholesale rejection of the clinical neuroendocrine strategies. Several key methodological issues received inadequate attention, and there have been calls to revisit this topic.

  11. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China.

    Science.gov (United States)

    Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Wang, Jin-Hui; Chen, Min-Hu; Chen, Jie

    2012-11-29

    Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65-75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

  12. Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation.

    Science.gov (United States)

    Gaab, Jens; Jiménez, Julia; Voneschen, Livia; Oschwald, Daniel; Meyer, Andrea H; Nater, Urs M; Krummenacher, Peter

    2016-01-01

    Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation. © 2017 S. Karger AG, Basel.

  13. 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.

  14. A Unique Case of Diffuse Metastatic Neuroendocrine Cancer with Subcutaneous Nodules on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computer Assisted Tomography

    International Nuclear Information System (INIS)

    Johnston, Mickaila J.; Sachedina, Archana; McDonald, James E.

    2015-01-01

    Neuroendocrine tumors (NETs) account for 8–10% of cases of carcinomas of unknown primary. Most of these cases are poorly differentiated with metastatic disease at the time of diagnosis. However, cutaneous metastatic presentation is rare. We present an interesting case of a 74-year-old woman presenting with cutaneous metastatic involvement from high grade poorly differentiated NET of unknown origin. She was referred to us with a diagnosis of lymphoma. 18 F-fluorodeoxyglucose positron emission tomography/computer assisted tomography imaging at our institution offered a differential diagnosis, including neuroendocrine cancer. Repeat skin lesion biopsy demonstrated “non-Merkel cell” carcinoma, favoring metastatic high-grade neuroendocrine carcinoma

  15. 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.

  16. The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity

    NARCIS (Netherlands)

    Meerlo, P; Horvath, KM; Nagy, GM; Bohus, B; Koolhaas, JM

    1999-01-01

    Environmental stimuli during early stages of life can influence the development of an organism and may result in permanent changes in adult behaviour and physiology. In the present study we investigated the influence of early postnatal handling on adult neuroendocrine and behavioural stress

  17. Thyroid hormone actions on male reproductive system of teleost fish.

    Science.gov (United States)

    Tovo-Neto, Aldo; da Silva Rodrigues, Maira; Habibi, Hamid R; Nóbrega, Rafael Henrique

    2018-04-17

    Thyroid hormones (THs) play important roles in the regulation of many biological processes of vertebrates, such as growth, metabolism, morphogenesis and reproduction. An increasing number of studies have been focused on the involvement of THs in the male reproductive system of vertebrates, in particular of fish. Therefore, this mini-review aims to summarize the main findings on THs role in male reproductive system of fish, focusing on sex differentiation, testicular development and spermatogenesis. The existing data in the literature have demonstrated that THs exert their roles at the different levels of the hypothalamic-pituitary-gonadal (HPG) axis. In general a positive correlation has been shown between THs and fish reproductive status; where THs are associated with testicular development, growth and maturation. Recently, the molecular mechanisms underlying the role of THs in spermatogenesis have been unraveled in zebrafish testis. THs promote germ cell proliferation and differentiation by increasing a stimulatory growth factor of spermatogenesis produced by Sertoli cells. In addition, THs enhanced the gonadotropin-induced androgen release in zebrafish testis. Next to their functions in the adult testis, THs are involved in the gonadal sex differentiation through modulating sex-related gene expression, and testicular development via regulation of Sertoli cell proliferation. In conclusion, this mini-review showed that THs modulate the male reproductive system during the different life stages of fish. The physiological and molecular mechanisms showed a link between the thyroid and reproduction, suggesting a possibly co-evolution and interdependence of these two systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Damholt, M B; Christensen, N J; Hilsted, Jannik

    2001-01-01

    within the normal range throughout the study. Altered neuroendocrine responses to hypoglycaemia may occur early in the course of type 1 diabetes. These are unlikely to be due to structural changes (i.e. autonomic neuropathy), but rather to changes in central nervous system activity patterns, i.......e. a higher threshold (i.e. a lower blood glucose level) for hypothalamic activation of the sympathoadrenal system.......Neuroendocrine responses (adrenaline, noradrenaline and pancreatic polypeptide (PP)) to hypoglycaemia are often diminished in long-term diabetic patients, but the role of autonomic nervous system changes in these reductions is not yet fully clarified. In order to establish whether such changes...

  19. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring

    Directory of Open Access Journals (Sweden)

    Clare M. Reynolds

    2017-09-01

    Full Text Available Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut–brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

  20. Effects of triclosan on hormones and reproductive axis in female Yellow River carp (Cyprinus carpio): Potential mechanisms underlying estrogen effect.

    Science.gov (United States)

    Wang, Fan; Guo, Xiangmeng; Chen, Wanguang; Sun, Yaowen; Fan, Chaojie

    2017-12-01

    Triclosan (TCS), a member of the class of compounds called pharmaceutical and personal care products (PPCPs), is a broad antibacterial and antifungal agent found in a lot of consumer products. However, TCS hormone effect mechanism in teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were exposed to 1/20, 1/10 and 1/5 LC 50 TCS (96h LC 50 of TCS to carp) under semi-static conditions for 42days. Vitellogenin (Vtg), 17β-estradiol (E 2 ), testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-β, GnRH, and Er by quantitative real-time PCR (qRT-PCR). The results indicated that 1/5 LC 50 TCS induced Vtg in hepatopancreas of female carps by interference with the hypothalamic-pituitary-gonadal (HPG) axis at multiple potential loci through three mechanisms: (a) TCS exposure enhanced the mRNA expression of hypothalamus and gonadal aromatase which converts androgens into estrogens, subsequently increasing serum concentrations of E 2 to induce Vtg in hepatopancreas; (b) TCS treatment increased GnRH and GtH-β mRNA expression and secretion, causing the disturbance of reproductive endocrine and the increase of E 2 to induce Vtg in hepatopancreas; (c) TCS exposure enhanced synthesis and secretion of Er, then it bound to Er to active Vtg synthesis. These mechanisms showed that TCS may induce Vtg production in female Yellow River carp by Er-mediated and non-Er-mediated pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

    Science.gov (United States)

    Carr, J.A.; Patino, R.

    2011-01-01

    Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health. ?? 2010 Elsevier Inc.

  2. The hypothalamus–pituitary–thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

    Science.gov (United States)

    Carr, J.A.; Patino, Reynaldo

    2011-01-01

    Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health.

  3. Should patients with laryngeal small cell neuroendocrine carcinoma receive prophylactic cranial irradiation?

    NARCIS (Netherlands)

    Coca-Pelaz, Andres; Devaney, Kenneth O.; Rodrigo, Juan P.; Halmos, Gyorgy B.; Strojan, Primoz; Mendenhall, William M.; Eisbruch, Avraham; Smee, Robert; Kusafuka, Kimihide; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    While small cell neuroendocrine carcinomas (SCNCs) most often arise in the lung, extrapulmonary SCNCs arise in a variety of locations-including the head and neck region. In particular, laryngeal SCNCs-while rare tumors-are nevertheless recognized as distinct lesions. The rarity of laryngeal SCNC

  4. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up.

    Science.gov (United States)

    Hörsch, Dieter; Ezziddin, Samer; Haug, Alexander; Gratz, Klaus Friedrich; Dunkelmann, Simone; Miederer, Matthias; Schreckenberger, Mathias; Krause, Bernd Joachim; Bengel, Frank M; Bartenstein, Peter; Biersack, Hans-Jürgen; Pöpperl, Gabriele; Baum, R P

    2016-05-01

    Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan-Meier curves and uni-variate log rank test Cox models. Median overall survival of all patients was 59 (95% confidence interval [CI] 49-68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83-5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79-5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41-12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18-0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9-46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71-4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow

  5. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich

    2009-01-01

    , in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14...... compared to both colorectal liver metastases (p=0.10) and normal liver tissue (p=0.06). In neuroendocrine tumors, gene-expression was highly variable of VEGF (530-fold), integrin alphaV (23-fold) and integrin beta3 (106-fold). Quantitative gene-expression levels of the key angiogenesis molecules VEGF......Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment...

  6. Neuroendocrine-immune and metabolic accompaniments of cholecystokinetic effects of balneotherapy on SPA Truskavets’

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    O M Marfiyan

    2015-05-01

    4Faculty of Physical Education, Health and Tourism, Kazimierz Wielki University, Bydgoszcz, Poland w.zukow@ukw.edu.pl   SUMMARY   Objective. Ability balneofactors spa Truskavets’ (Ukraine, including bioactive water Naftussya, affect Gall-bladder motility has long been known. We set a goal to identify changes related neuroendocrine-immune complex and metabolism accompanying cholecystokinetic effect of balneotherapy on spa. Results. In observation of 22 men with chronic cholecystitis in combination with pyelonephritis, found that 10-12-day course of balneotherapy (drinking of bioactive water Naftussya, application of ozokerite, mineral baths reduces Gall-bladder volume fasting by 16% (p0,05, by increasing PSD HF greater extent than LF. The basal levels of plasma cortisol decreased by 20% (p0,2 and 8% (p<0,05 respectively. Regarding immunity parameters revealed significant increase in blood CD16+ lymphocytes only (+17%, p<0,01 in the absence of changes in levels of CD3+CD4+ and CD3+CD8+ T cells and CD19+ B lymphocytes. Do not change significantly either serum Igg G, M, A, or circulating immune complexes. Finally, stated a slight but significant increase electrokinetic index cell nuclei of buccal epithelium, indicating the "rejuvenation" of the body. Conclusion: balneotherapy on spa Truskavets’ be significantly cholecystokinetic effect, combined with the activation excretory and depurative kidney functions and neutrophil bactericidal function against a background of lower levels of neuroendocrine markers of stress. Keywords: Truskavets’, balneotherapy, cholekinetic, diuresis, neuroendocrine-immune complex.

  7. The clinical implications and biologic relevance of neurofilament expression in gastroenteropancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Schimmack, Simon; Lawrence, Ben; Svejda, Bernhard; Alaimo, Daniele; Schmitz-Winnenthal, Hubertus; Fischer, Lars; Büchler, Markus W; Kidd, Mark; Modlin, Irvin

    2012-05-15

    Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit widely divergent behavior, limited biologic information (apart from Ki-67) is available to characterize malignancy. Therefore, the identification of alternative biomarkers is a key unmet need. Given the role of internexin alpha (INA) in neuronal development, the authors assessed its function in neuroendocrine cell systems and the clinical implications of its expression as a GEP-NEN biomarker. Functional assays were undertaken to investigate the mechanistic role of INA in the pancreatic BON cell line. Expression levels of INA were investigated in 50 pancreatic NENs (43 primaries, 7 metastases), 43 small intestinal NENs (25 primaries, 18 metastases), normal pancreas (n = 10), small intestinal mucosa (n = 16), normal enterochromaffin (EC) cells (n = 9), mouse xenografts (n = 4) and NEN cell lines (n = 6) using quantitative polymerase chain reaction, Western blot, and immunostaining analyses. In BON cells, decreased levels of INA messenger RNA and protein were associated with the inhibition of both proliferation and mitogen-activated protein kinase (MAPK) signaling. INA was not expressed in normal neuroendocrine cells but was overexpressed (from 2-fold to 42-fold) in NEN cell lines and murine xenografts. In pancreatic NENs, INA was overexpressed compared with pancreatic adenocarcinomas and normal pancreas (27-fold [P = .0001], and 9-fold [P = .02], respectively). INA transcripts were correlated positively with Ki-67 (correlation coefficient [r] = 0.5; P biologic information relevant to delineation of both pancreatic NEN tumor phenotypes and clinical behavior. Copyright © 2011 American Cancer Society.

  8. Defining global gene expression changes of the hypothalamic-pituitary-gonadal axis in female sGnRH-antisense transgenic common carp (Cyprinus carpio.

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    Jing Xu

    Full Text Available BACKGROUND: The hypothalamic-pituitary-gonadal (HPG axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus, 16 and 12 (pituitary, 119 and 93 (ovary, respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the

  9. Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

    Science.gov (United States)

    Xu, Jing; Huang, Wei; Zhong, Chengrong; Luo, Daji; Li, Shuangfei; Zhu, Zuoyan; Hu, Wei

    2011-01-01

    Background The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. Methodology/Principal Findings In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. Conclusions/Significance This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of

  10. When should genetic testing be performed in patients with neuroendocrine tumours?

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    O'Shea, Triona; Druce, Maralyn

    2017-12-01

    Neuroendocrine tumours (NETs) are a heterogenous group of tumours arising from neuroendocrine cells in several sites around the body. They include tumours of the gastroenteropancreatic system, phaeochromocytoma and paraganglioma and medullary thyroid cancer. In recent years, it has become increasingly apparent that a number of these tumours arise as a result of germline genetic mutations and are inherited in an autosomal dominant pattern. The number of genes implicated is increasing rapidly. Identifying which patients are likely to have a germline mutation enables clinicians to counsel patients adequately about their future disease risk, and allows for earlier detection of at-risk patients through family screening. The institution of screening and surveillance programmes may in turn lead to a major shift in presentation patterns for some of these tumours. In this review, we examine the features which may lead a clinician to suspect that a patient may have an inherited cause of a NET and we outline which underlying conditions should be suspected. We also discuss what type of screening may be appropriate in a variety of situations.

  11. F-18 FDG PET/CT imaging of primary hepatic neuroendocrine tumor

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    Katsuya Mitamura

    2015-01-01

    Full Text Available Primary hepatic neuroendocrine tumors (PHNETs are extremely rare neoplasms. Herein, we report a case of a 70-year-old man with a hepatic mass. The non-contrast computed tomography (CT image showed a low-density mass, and dynamic CT images indicated the enhancement of the mass in the arterial phase and early washout in the late phase. F18- fluorodeoxyglucose (18F-FDG positron emission tomography (PET and fused PET/CT images showed increased uptake in the hepatic mass. Whole-body 18F-FDG PET images showed no abnormal activity except for the liver lesion. Presence of an extrahepatic tumor was also ruled out by performing upper gastrointestinal endoscopy, total colonoscopy, and chest and abdominal CT. A posterior segmentectomy was performed, and histologic examination confirmed a neuroendocrine tumor (grade 1. The patient was followed up for about 2 years after the resection, and no extrahepatic lesions were radiologically found. Therefore, the patient was diagnosed with PHNET. To the best of our knowledge, no previous case of PHNET have been detected by 18F-FDG PET imaging.

  12. Diagnosis of Churg-Strauss Syndrome Presented With Neuroendocrine Carcinoma: A Case Report.

    Science.gov (United States)

    Park, Dayun; Lee, Ho Jun; Lee, Kwang Hoon; Kwon, Bum Sun; Park, Jin-Woo; Nam, Ki Yeun; Lee, Kyoung Hwan

    2017-06-01

    Churg-Strauss syndrome (CSS) is a rare systemic vasculitis that affect small and medium-sized blood vessels and is accompanied by asthma, eosinophilia, and peripheral neuropathy. This report describes a case of a 52-year-old man who had a history of sinusitis, asthma, and thymus cancer and who had complained of bilateral lower extremity paresthesia and weakness for a month. Peripheral neuropathy was detected by electrodiagnostic studies. Resection of a mediastinal mass, which was diagnosed as thymic neuroendocrine carcinoma, was performed five months before his visit. After thymectomy, peripheral blood tests revealed a gradual increase in eosinophils. Two months after surgery, he was admitted to the hospital for dyspnea, and nodules of focal consolidation were found in his chest X-ray. One month later, pyoderma occurred in the right shin, and the skin biopsy showed extravascular eosinophilic infiltration. He was diagnosed with CSS after thymectomy, and we report a very rare case of CSS presented with thymic neuroendocrine carcinoma.

  13. Treatment of pancreatic neuroendocrine tumor with liver metastases

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    LI Zhao

    2015-05-01

    Full Text Available Pancreatic neuroendocrine tumor (pNET is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is still the optimal treatment for resectable, well-differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis.

  14. Neuroendocrine Neoplasms of the Ovary: A Retrospective Study of the North Eastern German Society of Gynecologic Oncology (NOGGO).

    Science.gov (United States)

    Sehouli, Jalid; Woopen, Hannah; Pavel, Marianne; Richter, Rolf; Lauterbach, Lisa-Kathrin; Taube, Eliane; Darb-Esfahani, Silvia; Fotopoulou, Christina; Pietzner, Klaus

    2016-03-01

    Neuroendocrine neoplasms (NEN) of the female genital tract account for 2% of gynecological cancers. The aim of this study was to share our experience of 11 primary neuroendocrine neoplasms of the ovary. All patients who presented and/or were treated at our Institution with histologically-confirmed NEN of the ovary were included. Clinical data including tumor stage, diagnostic and therapeutic management and survival were assessed. Pathological specimens were critically reviewed. We identified 11 patients with NEN of the ovary consisting of nine neuroendocrine cancers and two carcinoids. Median age was 55.9 years. NEN were mostly poorly differentiated (72.4%). Primary surgery was performed in all patients. Adjuvant chemotherapy was administered in five patients consisting of platinum-based regimens. Median overall survival was 20 months. We propose a diagnostic algorithm for NEN of the ovary and discuss possible treatments according to FIGO stages. Patients should be included in multicenter studies whenever possible. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Clinical Presentation and Diagnosis of Neuroendocrine Tumors.

    Science.gov (United States)

    Vinik, Aaron I; Chaya, Celine

    2016-02-01

    Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor.

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    Hope, Thomas A; Pampaloni, Miguel Hernandez; Nakakura, Eric; VanBrocklin, Henry; Slater, James; Jivan, Salma; Aparici, Carina Mari; Yee, Judy; Bergsland, Emily

    2015-08-01

    To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

  17. Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

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    Singh S

    2014-08-01

    Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

  18. The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

    LENUS (Irish Health Repository)

    O'Connor, T M

    2012-02-03

    Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)\\/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

  19. Clinical relevance of F-18 FDG PET for imaging of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Adams, S.; Baum, R.P.; Hoer, G.

    2001-01-01

    Neuroendocrine tumors are characterized immunocytochemically by the expression of different peptides and biogenic amines. Hormones induce their biological action by binding to and stimulating specific membrane-associated receptors for e.g. somatostatin. The presence of somatostatin receptors (SR) has been described mainly in endocrine glands and the central nervous system. Interestingly, a large variety of human tumors, including gastroenteropancreatic (GEP) tumors and medullary thyroid carcinomas (MTC) also express a high density of SR and can be imaged with [ 111 In-DTPA-D-Phe 1 ]-pentetreotide. Cell proliferative activity is an important indicator of the growth of various malignant tumors associated with a poorer prognosis and Ki-67 expression. 18 F-FDG is a marker of tumor viability, based upon the increased glycolysis that is associated with malignancy as compared with normal tissue. SR-containing neuroendocrine tumors are well-differentiated and tend to grow slowly. Furthermore, these tumors demonstrate inverse relationship between in vivo SR expression, cell proliferation (low Ki-67 expression) and FDG uptake (normal biodistribution). In comparison, less differentiated tumors, e.g. atypical carcinoids or MTC with increasing CEA levels show mitotic activity (high levels of Ki-67 immunoreactivity and increased FDG uptake) and often lack of SR. In conclusion, SR scintigraphy has been shown to localize well-differentiated neuroendocrine tumors. In contrast, PET imaging is valuable for predicting malignancy only in less differentiated tumors with increased glucose metabolism. Therefore, an additional F-18 FDG PET should be performed if SR scintigraphy (GEP tumors) or combined imaging using [ 111 In-DTPA-D-Phe 1 ]-pentetreotide and 99m Tc(V)-DMSA (MTC) is negative. (orig.) [de

  20. Rethinking reproductive "tourism" as reproductive "exile".

    Science.gov (United States)

    Inhorn, Marcia C; Patrizio, Pasquale

    2009-09-01

    Whereas reproductive "tourism" implies leisure travel, reproductive "exile" bespeaks the numerous difficulties and constraints faced by infertile patients who are "forced" to travel globally for assisted reproduction. Given this reality, it is time to rethink the language of "reproductive tourism," replacing it with more accurate and patient-centered terms.

  1. Gastric neuroendocrine tumours.

    Science.gov (United States)

    Crosby, David A; Donohoe, Claire L; Fitzgerald, Louise; Muldoon, Cian; Hayes, Brian; O'Toole, Dermot; Reynolds, John V

    2012-01-01

    Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment. Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs. Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted. Copyright © 2012 S. Karger AG, Basel.

  2. 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.

  3. Giant type III well-differentiated neuroendocrine tumor of the stomach: A case report

    Directory of Open Access Journals (Sweden)

    Omar Bellorin

    2016-01-01

    Conclusion: The incidence of gastric neuroendocrine tumors has been increasing during the last decade, underscoring the need to improve our understanding of their biology and behavior. When identified histologically, patient outcomes depend on appropriate determination of tumor biology and subsequent choice of treatment.

  4. Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome.

    Science.gov (United States)

    Caldwell, Aimee S L; Edwards, Melissa C; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B; Handelsman, David J; Walters, Kirsty A

    2017-04-18

    Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS.

  5. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995–2012 in South China

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    Wang Yu-hong

    2012-11-01

    Full Text Available Abstract Background Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN is the most common type of neuroendocrine tumors accounting for 65–75% of neuroendocrine neoplasms (NENs. Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Methods Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Results Pancreas was found the most common site of involvement (34.8%. 149 patients (83.7% presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%; carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA and synaptophysin (Syn immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5% had G1 tumors, 31(18.3% G2 tumors and 51 (30.2% G3 tumors. Neuroendocrine tumor (NET, neuroendocrine carcinoma (NEC and mixed adenoendocrine carcinoma (MANEC were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4% patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Conclusions Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

  6. Kisspeptin as a master player in the central control of reproduction in mammals: an overview of kisspeptin research in domestic animals.

    Science.gov (United States)

    Okamura, Hiroaki; Yamamura, Takashi; Wakabayashi, Yoshihiro

    2013-05-01

    The hypothalamo-pituitary-gonadal (HPG) axis is the regulatory system for reproduction in mammals. Because secretion of gonadotropin-releasing hormone (GnRH) into the portal vessels is the final step at which the brain controls gonadal activities, the GnRH neuronal system had been thought to be central to the HPG axis. A newly discovered neural peptide, kisspeptin, has opened a new era in reproductive neuroendocrinology. As shown in a variety of mammals, kisspeptin is a potent endogenous secretagogue of GnRH, and the kisspeptin neuronal system governs both the pulsatile GnRH secretion that drives folliculogenesis, spermatogenesis and steroidogenesis, and the GnRH surge that triggers ovulation in females. The kisspeptin neuronal system is therefore considered a master player in the central control of mammalian reproduction, and kisspeptin and related substances could therefore be valuable for the development of novel strategies for the management of fertility in farm animals. To this end, the present review aimed to summarize the current research on kisspeptin signaling with a focus on domestic animals such as sheep, goats, cattle, pigs and horses. © 2013 Japanese Society of Animal Science.

  7. Effect of temperature on development and the histology of the neuroendocrine system of the tettigoniid, Jamaicana flava (Caudell)

    Energy Technology Data Exchange (ETDEWEB)

    Peacock, A J; Anstee, J H; Bowler, K

    1977-01-01

    The effect of various constant temperatures on the rate of development and histology of the neuroendocrine system have been studied in sixth instar larvae of Jamaicana flava. Changes in the histology of the neuroendocrine system are discussed in relation to parallel changes in the rate of development. Temperature increases the rate up to a maximum beyond which further increases are not effective in terms of acceleration of development. For Jamaicana this rate is maximal at ca. 30/sup 0/C, higher temperatures producing a reduction in the rate of development.

  8. Utility of thallium-201 and iodine-123 metaiodobenzylguanidine in the scintigraphic detection of neuroendocrine neoplasia

    International Nuclear Information System (INIS)

    Montravers, F.; Coutris, G.; Sarda, L.; Mensch, B.; Talbot, J.N.

    1993-01-01

    In order to determine whether the association of the two markers is able to improve the detection of neuroendocrine lesions, 137 sctinigraphic examinations using MIBG and thallium were performed in 101 patients referred for suspicion or follow-up of neuroendocrine tumours. Thallium chloride was first injected (1 MBq/kg), images being acquired about 20 min after injection; 123 I-MIBG (4 MBq/kg) was then injected and images acquired 5 and 24 h later. In patients with phaeochromocytoma or neuroblastoma, thallium scintigraphy appeared of little help since no tumoural site was discovered by thallium accumulation alone. In contrast, thallium examination seemed of interest in the detection of paraganglioma and MTC, the association of the two radiopharmaceuticals increasing the number of detected sites. (orig./MTG)

  9. Combined Primary Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver

    Directory of Open Access Journals (Sweden)

    Chii-Shuenn Yang

    2009-08-01

    Full Text Available We report a unique case of combined primary neuroendocrine carcinoma (NEC and hepatocellular carcinoma (HCC of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.

  10. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Loft, Annika

    2010-01-01

    PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors. EXPERIMENTAL DESIGN: Ninety...

  11. 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...

  12. Hypothalamic-pituitary-adrenal axis activity is not elevated in a songbird (Junco hyemalis) preparing for migration.

    Science.gov (United States)

    Bauer, Carolyn M; Needham, Katie B; Le, Chuong N; Stewart, Emily C; Graham, Jessica L; Ketterson, Ellen D; Greives, Timothy J

    2016-06-01

    During spring, increasing daylengths stimulate gonadal development in migratory birds. However, late-stage reproductive development is typically postponed until migration has been completed. The hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids, which have been associated with pre-migratory hyperphagia and fattening. The HPA-axis is also known to suppress the hypothalamic-pituitary-gonadal (HPG) axis, suggesting the possibility that final transition into the breeding life history stage may be slowed by glucocorticoids. We hypothesized that greater HPA-axis activity in individuals preparing for migration may foster preparation for migration while simultaneously acting as a "brake" on the development of the HPG-axis. To test this hypothesis, we sampled baseline corticosterone (CORT), stress-induced CORT, and negative feedback efficacy of Dark-eyed Juncos (Junco hyemalis) in an overwintering population that included both migratory (J.h. hyemalis) and resident (J.h. carolinensis) individuals. We predicted that compared to residents, migrants would have higher baseline CORT, higher stress-induced CORT, and weaker negative feedback. Juncos were sampled in western Virginia in early March, which was about 2-4wk before migratory departure for migrants and 4-5wk before first clutch initiation for residents. Contrary to our predictions, we found that migrants had lower baseline and stress-induced CORT and similar negative feedback efficacy compared with residents, which suggests that delayed breeding in migrants is influenced by other physiological mechanisms. Our findings also suggest that baseline CORT is not elevated during pre-migratory fattening, as migrants had lower baseline CORT and were fatter than residents. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Study of the neuroendocrine and immunologic mechanism of fatigue caused by military operations

    Directory of Open Access Journals (Sweden)

    Xin LI

    2012-01-01

    Full Text Available Objective  To observe the regularity of the changes in neuroendocrine-immune system caused by fatigue due to military operations, and explore the mechanism by which fatigue occurs in military operations. Methods  The subjects were 240 soldiers belonging to a field artillery force. The medical history and physical examination were taken before military operations, and fatigue assessment scale was accomplished as well. The following variables were measured in all the subjects: pituitary-adrenal [adrenocorticotropic hormone (ACTH, cortical hormone (B, 24-h urinary free cortisol (UFC], pituitary-gonadal [luteinizing hormone (LH, testosterone (T, estradiol (E2], pituitary-thyroid functions [serum thyroid stimulating hormone (TSH, tetraiodothyronine (TT4, triiodothyronine (TT3, free thyroxine (FT4, and free triiodothyronine (FT3], and cellular immune parameters (CD3+, CD4+, CD8+, CD4+/CD8+, B, NK. After 7 d of large-scale and high-intensity field exercises, the above variables were again measured in all the subjects. Results  After high-intensity military operations, the unpleasant feelings were significantly increased, and the compulsive and psychotic scores significantly decreased in the soldiers. In addition, the pituitary-adrenal and pituitary-gonadal hormone levels also decreased (all PPPConclusion  The depressed psychological tolerance in soldiers is the psychological factor of fatigue after a high-intensity military operation. The hypocorticoidism and inhibition of hypothalamic-pituitary-gonadal axis are the pathophysiological basis of military operation fatigue. Suppression of immune function is an important reason for an increase of susceptibility to disease after high-intensity military operations.

  14. Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a Metabolic Checkpoint and Gateway to Reproductive Competence

    Directory of Open Access Journals (Sweden)

    Angela K. Odle

    2018-01-01

    Full Text Available The adipokine leptin signals the body’s nutritional status to the brain, and particularly, the hypothalamus. However, leptin receptors (LEPRs can be found all throughout the body and brain, including the pituitary. It is known that leptin is permissive for reproduction, and mice that cannot produce leptin (Lep/Lep are infertile. Many studies have pinpointed leptin’s regulation of reproduction to the hypothalamus. However, LEPRs exist at all levels of the hypothalamic–pituitary–gonadal axis. We have previously shown that deleting the signaling portion of the LEPR specifically in gonadotropes impairs fertility in female mice. Our recent studies have targeted this regulation to the control of gonadotropin releasing hormone receptor (GnRHR expression. The hypotheses presented here are twofold: (1 cyclic regulation of pituitary GnRHR levels sets up a target metabolic checkpoint for control of the reproductive axis and (2 multiple checkpoints are required for the metabolic signaling that regulates the reproductive axis. Here, we emphasize and explore the relationship between the hypothalamus and the pituitary with regard to the regulation of GnRHR. The original data we present strengthen these hypotheses and build on our previous studies. We show that we can cause infertility in 70% of female mice by deleting all isoforms of LEPR specifically in gonadotropes. Our findings implicate activin subunit (InhBa mRNA as a potential leptin target in gonadotropes. We further show gonadotrope-specific upregulation of GnRHR protein (but not mRNA levels following leptin stimulation. In order to try and understand this post-transcriptional regulation, we tested candidate miRNAs (identified with in silico analysis that may be binding the Gnrhr mRNA. We show significant upregulation of one of these miRNAs in our gonadotrope-Lepr-null females. The evidence provided here, combined with our previous work, lay the foundation for metabolically regulated post

  15. Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System of Female Olive Flounder Paralichthys olivaceus.

    Science.gov (United States)

    Kim, Hyun Chul; Lee, Chi Hoon; Hur, Sung Pyu; Kim, Byeong Hoon; Park, Jun Young; Lee, Young Don

    2015-03-01

    This study investigated possible involvement of photoperiodic regulation in reproductive endocrine system of female olive flounder. To investigate the influence on brain-pituitary axis in endocrine system by regulating photoperiod, compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-β, LH-β and GH mRNA in pituitary before and after spawning. Photoperiod was treated natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase) was inhibited gonadal development of female olive flounder. In natural photoperiod group, the Kiss2 expression level a significant declined in Mar. (spawning period). And also, FSH-β, LH-β and GH mRNA expression levels were increasing at this period. However, in long photoperiod group, hypothalamic Kiss2, FSH-β, LH-β and GH mRNA expression levels did not show any significant fluctuation. These results suggest that expression of hypothalamic Kiss2, GtH and GH in the pituitary would change in response to photoperiod and their possible involvement of photoperiodic regulation in reproductive endocrine system of the BPG axis.

  16. Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

    Science.gov (United States)

    Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

    2016-01-01

    Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

  17. Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity.

    Science.gov (United States)

    Whitaker, Annie M; Gilpin, Nicholas W

    2015-08-01

    Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. Copyright © 2015. Published by Elsevier Inc.

  18. EVOLUTION OF NEUROENDOCRINE CELL POPULATION AND PEPTIDERGIC INNERVATION, ASSESSED BY DISCRIMINANT ANALYSIS, DURING POSTNATAL DEVELOPMENT OF THE RAT PROSTATE

    Directory of Open Access Journals (Sweden)

    Rosario Rodríguez

    2011-05-01

    Full Text Available Serotonin immunoreactive neuroendocrine cells and peptidergic nerves (NPY and VIP could have a role in prostate growth and function. In the present study, rats grouped by stages of postnatal development (prepubertal, pubertal, young and aged adults were employed in order to ascertain whether age causes changes in the number of serotoninergic neuroendocrine cells and the length of NPY and VIP fibres. Discriminant analysis was performed in order to ascertain the classificatory power of stereologic variables (absolute and relative measurements of cell number and fibre length on age groups. The following conclusions were drawn: a discriminant analysis confirms the androgen-dependence of both neuroendocrine cells and NPYVIP innervation during the postnatal development of the rat prostate; b periglandular innervation has more relevance than interglandular innervation in classifying the rats in age groups; and c peptidergic nerves from ventral, ampullar and periductal regions were more age-dependent than nerves from the dorso-lateral region.

  19. 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.

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

    International Nuclear Information System (INIS)

    Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

    2013-01-01

    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

  1. Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

    NARCIS (Netherlands)

    Jilesen, Anneke P. J.; van Eijck, Casper H. J.; Busch, Olivier R. C.; van Gulik, Thomas M.; Gouma, Dirk J.; van Dijkum, Els J. M. Nieveen

    2016-01-01

    Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic

  2. Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms

    OpenAIRE

    Tan, Huangying

    2016-01-01

    Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from the endocrine cells of stomach. Most g-NENs progresses slowly and have a long disease course; however, some other g-NENs grow rapidly, similar to the progression of gastric adenocarcinoma. g-NENs have complex and diverse clinical manifestations and their prognosis and treatment strategies depend highly on clinical subtype, pathological grade, tumour stage, and other factors. Due to their low prevalence,...

  3. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    Science.gov (United States)

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  4. Reproductive effort and the egg number vs. size trade-off in Physalaemus frogs (Anura: Leiuperidae)

    Science.gov (United States)

    Camargo, Arley; Sarroca, Macarena; Maneyro, Raúl

    2008-09-01

    Patterns of reproductive allocation are expected to differ between species according to temporally and spatially variable costs of reproduction. Even when reproductive allocation patterns are the same, species can also differ in how the reproductive effort is allocated between offspring number and size. In this study, we compared the reproductive allocation patterns and the offspring number vs. size trade-off in two frog species, Physalaemus biligonigerus and P. gracilis, using bivariate (standardized major axis) and multiple linear regressions. Both species showed a common slope between body size and reproductive effort and thus a similar allocation pattern although P. biligonigerus has a larger body size (shift along common slope) and makes a lower reproductive effort (shift in intercept) than P. gracilis. We suggest that similar allocation patterns may be related to the shared phenologies of these frogs and that the differences in reproductive effort could represent either an adaptive shift (e.g., change in body space for the clutch) or a historical constraint. There was a negative correlation between fecundity and egg size in P. biligonigerus but not in P. gracilis as predicted by the acquisition-allocation model (Y-model). This study constitutes the first valid test of the Y-model based on recent predictions derived for the trade-off between offspring size vs. number. We conclude that future studies should compare reproductive allocation patterns between species using tests of allometric slopes with appropriate phylogenetic control to detect both adaptive shifts in allocation strategies and correlations with other life-history traits.

  5. Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin

    Directory of Open Access Journals (Sweden)

    Mulet-Margalef N

    2012-09-01

    Full Text Available Núria Mulet-Margalef, Jaume CapdevilaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainAbstract: For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase-AKT-mTOR pathway.Keywords: pancreatic neuroendocrine tumors, everolimus, targeted therapies

  6. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors.

    Science.gov (United States)

    Norton, Jeffrey A; Kivlen, Maryann; Li, Michelle; Schneider, Darren; Chuter, Timothy; Jensen, Robert T

    2003-08-01

    There is considerable controversy about the treatment of patients with malignant advanced neuroendocrine tumors of the pancreas and duodenum. Aggressive surgery remains a potentially efficacious antitumor therapy but is rarely performed because of its possible morbidity and mortality. Aggressive resection of advanced neuroendocrine tumors can be performed with acceptable morbidity and mortality rates and may lead to extended survival. The medical records of patients with advanced neuroendocrine tumors who underwent surgery between 1997 and 2002 by a single surgeon at the University of California, San Francisco, were reviewed in an institutional review board-approved protocol. Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates were recorded. Disease-free survival was defined as no tumor identified on radiological imaging studies and no detectable abnormal hormone levels. Proportions were compared statistically using the Fisher exact test. Kaplan-Meier curves were used to estimate survival rates. Twenty patients were identified (11 men and 9 women). Of these, 10 (50%) had gastrinoma, 1 had insulinoma, and the remainder had nonfunctional tumors; 2 had multiple endocrine neoplasia type 1, and 1 had von Hippel-Lindau disease. The mean age was 55 years (range, 34-72 years). In 10 patients (50%), tumors were thought to be unresectable according to radiological imaging studies because of multiple bilobar liver metastases (n = 6), superior mesenteric vein invasion (n = 3), and extensive nodal metastases (n = 1). Tumors were completely removed in 15 patients (75%). Surgical procedures included 8 proximal pancreatectomies (pancreatoduodenectomy or whipple procedure), 3 total pancreatectomies, 9 distal pancreatectomies, and 3 tumor enucleations from the pancreatic head. Superior mesenteric vein reconstruction was done in 3 patients. Liver resections were done in 6 patients, and an extended periaortic node

  7. Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

    Directory of Open Access Journals (Sweden)

    Emmanuelle A. D. Schindler

    2018-03-01

    Full Text Available Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

  8. Role of changes in functional status of hypothalamic-pituitary-adrenocortical axis in immunoenhancement after low dose radiation

    International Nuclear Information System (INIS)

    Liu Shuzheng; Zhao Yong; Han Zhenbo

    1994-01-01

    Whole-body irradiation (WBI) of mice with 75 mGy X-rays caused increase in 5-hydroxytryptamine (5HT) content of hypothalamus and decrease in serum adrenocorticotropic hormone (ACTH) and corticosterone (CS) level, accompanied with potentiation of immune functions, expressed as increased spontaneous incorporation of 3 H-TdR into thymocytes, augmented proliferative reaction of the splenocytes to Con A and increased production of interleukin-2 by the splenocytes. After intra hypothalamic injection of 5HT there occurred a lowering of serum ACTH level and enhancement of immune reactivity of the splenic and thymic lymphocytes. It is assumed that low dose radiation could influence the central 5-hydroxytryptaminergic neurons causing increase in hypothalamic 5HT content and this, in turn, decreases pituitary secretion of ACTH with a down-regulation of the adrenocortical function. This would partially release the tonic suppression normally exerted on the immune organs by the hypothalamic-pituitary-adrenocortical axis, thus leading to potentiation of immune functions. These neuroendocrine changes should be considered as an important factor in the analysis of the mechanism of immunoenhancement after WBI with low doses

  9. Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

    NARCIS (Netherlands)

    A.P.J. Jilesen (Anneke P. J.); C.H.J. van Eijck (Casper); O.R.C. Busch (Olivier); T.M. van Gulik (Thomas); D.J. Gouma (Dirk); E.J.M.N. Van Dijkum (Els J. M. Nieveen)

    2016-01-01

    textabstractBackground: Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of

  10. Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light.

    Science.gov (United States)

    Bertolesi, Gabriel E; Vazhappilly, Sherene T; Hehr, Carrie L; McFarlane, Sarah

    2016-03-01

    Light-regulated skin colour change is an important physiological process in invertebrates and lower vertebrates, and includes daily circadian variation and camouflage (i.e. background adaptation). The photoactivation of melanopsin-expressing retinal ganglion cells (mRGCs) in the eye initiates an uncharacterized neuroendocrine circuit that regulates melanin dispersion/aggregation through the secretion of alpha-melanocyte-stimulating hormone (α-MSH). We developed experimental models of normal or enucleated Xenopus embryos, as well as in situ cultures of skin of isolated dorsal head and tails, to analyse pharmacological induction of skin pigmentation and α-MSH synthesis. Both processes are triggered by a melanopsin inhibitor, AA92593, as well as chloride channel modulators. The AA9253 effect is eye-dependent, while functional data in vivo point to GABAA receptors expressed on pituitary melanotrope cells as the chloride channel blocker target. Based on the pharmacological data, we suggest a neuroendocrine circuit linking mRGCs with α-MSH secretion, which is used normally during background adaptation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Variation in the ovine cortisol response to systemic bacterial endotoxin challenge is predominantly determined by signalling within the hypothalamic-pituitary-adrenal axis

    International Nuclear Information System (INIS)

    You Qiumei; Karrow, Niel A.; Cao Honghe; Rodriguez, Alexander; Mallard, Bonnie A.; Boermans, Herman J.

    2008-01-01

    Bi-directional communication between the neuroendocrine and immune systems is designed, in part, to maintain or restore homeostasis during physiological stress. Exposure to endotoxin during Gram-negative bacterial infection for example, elicits the release of pro-inflammatory cytokines that activate the hypothalamic-pituitary-adrenal axis (HPAA). The secretion of adrenal glucocorticoids subsequently down regulates the host inflammatory response, minimizing potential tissue damage. Sequence and epigenetic variants in genes involved in regulating the neuroendocrine and immune systems are likely to contribute to individual differences in the HPAA response, and this may influence the host anti-inflammatory response to toxin exposure and susceptibility to inflammatory disease. In this study, high (HCR) and low (LCR) cortisol responders were selected from a normal population of 110 female sheep challenged iv with Escherichia coli endotoxin (400 ng/kg) to identify potential determinants that contribute to variation in the cortisol response phenotype. This phenotype was stable over several years in the HCR and LCR animals, and did not appear to be attributed to differences in expression of hepatic immune-related genes or systemic pro-inflammatory cytokine concentrations. Mechanistic studies using corticotrophin-releasing factor (0.5 μg/kg body weight), arginine vasopressin (0.5 μg/kg), and adrenocorticotropic hormone (0.5 μg/kg) administered iv demonstrated that variation in this phenotype is largely determined by signalling within the HPAA. Future studies will use this ovine HCR/LCR model to investigate potential genetic and epigenetic variants that may contribute to variation in cortisol responsiveness to bacterial endotoxin

  12. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    Energy Technology Data Exchange (ETDEWEB)

    Milione, Massimo [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pusceddu, Sara [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Gasparini, Patrizia [Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Melotti, Flavia [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Maisonneuve, Patrick [Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141 (Italy); Mazzaferro, Vincenzo [Division of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Braud, Filippo G. de [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pelosi, Giuseppe, E-mail: giuseppe.pelosi@unimi.it [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Department of Medicine, Surgery and Dentistry, Università degli Studi, Facoltà di Medicina, Milan 20122 (Italy)

    2012-08-16

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.

  13. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    International Nuclear Information System (INIS)

    Milione, Massimo; Pusceddu, Sara; Gasparini, Patrizia; Melotti, Flavia; Maisonneuve, Patrick; Mazzaferro, Vincenzo; Braud, Filippo G. de; Pelosi, Giuseppe

    2012-01-01

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene

  14. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

    Science.gov (United States)

    Eustache, Florence; Mondon, Françoise; Canivenc-Lavier, Marie Chantal; Lesaffre, Corinne; Fulla, Yvonne; Berges, Raymond; Cravedi, Jean Pierre; Vaiman, Daniel; Auger, Jacques

    2009-08-01

    The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

  15. Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma.

    Science.gov (United States)

    Kervarrec, Thibault; Samimi, Mahtab; Gaboriaud, Pauline; Gheit, Tarik; Beby-Defaux, Agnès; Houben, Roland; Schrama, David; Fromont, Gaëlle; Tommasino, Massimo; Le Corre, Yannick; Hainaut-Wierzbicka, Eva; Aubin, Francois; Bens, Guido; Maillard, Hervé; Furudoï, Adeline; Michenet, Patrick; Touzé, Antoine; Guyétant, Serge

    2018-05-01

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as "combined" or "conventional." Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of

  16. Developmental Origin of Reproductive and Metabolic Dysfunctions: Androgenic Versus Estrogenic Reprogramming

    Science.gov (United States)

    Padmanabhan, Vasantha; Veiga-Lopez, Almudena

    2013-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common fertility disorders, affecting several million women worldwide. Women with PCOS manifest neuroendocrine, ovarian, and metabolic defects. A large number of animal models have evolved to understand the etiology of PCOS. These models provide support for the contributing role of excess steroids during development in programming the PCOS phenotype. However, considerable phenotypic variability is evident across animal models, depending on the quality of the steroid administered and the perinatal time of treatment relative to the developmental trajectory of the fetus/offspring. This review focuses on the reproductive and metabolic phenotypes of the various PCOS animal models that have evolved in the last decade to delineate the relative roles of androgens and estrogens in relation to the timing of exposure in programming the various dysfunctions that are part and parcel of the PCOS phenotype. Furthermore, the review addresses the contributory role of the postnatal metabolic environment in exaggerating the severity of the phenotype, the translational relevance of the various animal models to PCOS, and areas for future research. PMID:21710394

  17. Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

    Science.gov (United States)

    Finn, David P; Hudson, Alan L; Kinoshita, Hiroshi; Coventry, Toni L; Jessop, David S; Nutt, David J; Harbuz, Michael S

    2004-03-01

    Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

  18. Mechanical impedance of the sitting human body in single-axis compared to multi-axis whole-body vibration exposure.

    Science.gov (United States)

    Holmlund, P; Lundström, R

    2001-01-01

    The study was aimed to investigate the mechanical impedance of the sitting human body and to compare data obtained in laboratory single-axis investigations with multi-axis data from in vehicle measurements. The experiments were performed in a laboratory for single-axis measurements. The multi-axis exposure was generated with an eight-seat minibus where the rear seats had been replaced with a rigid one. The subjects in the multi-axis experiment all participated in the single-axis experiments. There are quite a few investigations in the literature describing the human response to single-axis exposure. The response from the human body can be expected to be affected by multi-axis input in a different way than from a single-axis exposure. The present knowledge of the effect of multiple axis exposure is very limited. The measurements were performed using a specially designed force and accelerometer plate. This plate was placed between the subject and the hard seat. Outcome shows a clear difference between mechanical impedance for multi-axis exposure compared to single-axis. This is especially clear in the x-direction where the difference is very large. The conclusion is that it seems unlikely that single-axis mechanical impedance data can be directly transferred to a multi-axis environment. This is due to the force cross-talk between different directions.

  19. Developmental reprogramming of reproductive and metabolic dysfunction in sheep: native steroids vs. environmental steroid receptor modulators

    Science.gov (United States)

    Padmanabhan, Vasantha; Sarma, Hiren N.; Savabieasfahani, Mozhgan; Steckler, Teresa L.; Veiga-Lopez, Almudena

    2014-01-01

    The inappropriate programming of developing organ systems by exposure to excess native or environmental steroids, particularly the contamination of our environment and our food sources with synthetic endocrine disrupting chemicals that can interact with steroid receptors, is a major concern. Studies with native steroids have found that in utero exposure of sheep to excess testosterone, an estrogen precursor, results in low birth weight offspring and leads to an array of adult reproductive / metabolic deficits manifested as cycle defects, functional hyperandrogenism, neuroendocrine / ovarian defects, insulin resistance, and hypertension. Furthermore, the severity of reproductive dysfunction is amplified by excess postnatal weight gain. The constellation of adult reproductive and metabolic dysfunction in prenatal testosterone-treated sheep is similar to features seen in women with polycystic ovary syndrome. Prenatal dihydrotestosterone treatment failed to result in similar phenotype suggesting that many effects of prenatal testosterone excess are likely facilitated via aromatization to estradiol. Similarly, exposure to environmental steroid imposters such as bisphenol A (BPA) and methoxychlor (MXC) from days 30-90 of gestation had long-term but differential effects. Exposure of sheep to BPA, which resulted in maternal levels of 30-50 ng/ml BPA, culminated in low birth-weight offspring. These female offspring were hypergonadotropic during early postnatal life and characterized by severely dampened preovulatory LH surges. Prenatal MXC-treated females had normal birth weight and manifested delayed but normal amplitude LH surges. Importantly, the effects of BPA were evident at levels, which approximated twice the highest levels found in human maternal circulation of industrialized nations. These findings provide evidence in support of developmental origin of adult reproductive and metabolic diseases and highlight the risk posed by exposure to environmental endocrine

  20. Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2015-11-15

    Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

  1. Changing reproductive effort within a semelparous reproductive episode.

    Science.gov (United States)

    Hughes, P William; Simons, Andrew M

    2014-08-01

    • Life-history theory predicts a trade-off between current and future reproduction for iteroparous organisms-as individuals age, the expected value of future reproduction declines, and thus reproductive effort is expected to be higher in later clutches than in earlier. In contrast, models explaining the evolution of semelparity treat semelparous reproduction as instantaneous, with no scope for intraindividual variation. However, semelparous reproduction is also extended, but over shorter time scales; whether there are similar age- or stage-specific changes in reproductive effort within a semelparous episode is unclear. In this study, we assessed whether semelparous individuals increase reproductive effort as residual reproductive value declines by comparing the reproductive phenotype of flowers at five different floral positions along a main inflorescence.• Using the herbaceous monocarp Lobelia inflata, we conducted a longitudinal study of 409 individuals including both laboratory and field populations over three seasons. We recorded six reproductive traits-including the length of three phenological intervals as well as fruit size, seed size, and seed number-for all plants across floral positions produced throughout the reproductive episode.• We found that while the rate of flower initiation did not change, flowers at distal (late) floral positions developed more quickly and contained larger seed than flowers at basal (early) floral positions did.• Our results were consistent with the hypothesis that, like iteroparous organisms, L. inflata increases reproductive effort in response to low residual reproductive value. © 2014 Botanical Society of America, Inc.

  2. Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Robert Grützmann

    2010-11-01

    Full Text Available Pancreatic neuroendocrine tumors (PNETs are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET or by symptoms related to tumor bulk effects (non-functional PNET. So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management.

  3. Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

    International Nuclear Information System (INIS)

    Ehehalt, Florian; Franke, Ellen; Pilarsky, Christian; Grützmann, Robert

    2010-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management

  4. Guideline for PET/CT imaging of neuroendocrine neoplasms withGa-DOTA-conjugated somatostatin receptor targeting peptides andF-DOPA

    DEFF Research Database (Denmark)

    Bozkurt, Murat Fani; Virgolini, Irene; Balogova, Sona

    2017-01-01

    PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing......, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using68Ga-DOTA-conjugated peptides, as well as18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with68Ga...

  5. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

    OpenAIRE

    Lee, Richard; Sawa, Akira

    2014-01-01

    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  6. An Eustachian Tube Neuroendocrine Carcinoma: A Previously Undescribed Entity and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gavin J. le Nobel

    2016-01-01

    Full Text Available Primary sinonasal and middle ear neuroendocrine carcinomas are rare malignancies of the head and neck. Owing to the rarity of these tumors, the clinical behavior and optimal management of these tumors are not well defined. We present a case of an incidentally discovered sinonasal neuroendocrine carcinoma that was found to originate from the Eustachian tube, which has not previously been described in the literature. This patient was treated with primary surgical resection using a combination of transnasal and transaural approaches and achieved an incomplete resection. Follow-up imaging demonstrated continued tumor growth in the Eustachian tube as well as a new growth in the ipsilateral cerebellopontine angle and findings suspicious of perineural invasion. However, the tumor exhibited a benign growth pattern and despite continued growth the patient did not receive additional treatment and he remains asymptomatic 35 months following his original surgery.

  7. Nutrition and reproduction in women.

    Science.gov (United States)

    2006-01-01

    Malnutrition is a major problem in developing countries, and obesity and eating disorders are increasingly common in developing as well as developed countries. The reproductive axis is closely linked to nutritional status, especially undernutrition in the female, and inhibitory pathways involving detectors in the hind brain suppress ovulation in subjects with weight loss. Recovery may occur after minimal reacquisition of weight because energy balance is more important than body fat mass. Anorexia nervosa and bulimia nervosa affect up to 5% of women of reproductive age causing amenorrhoea, infertility and, in those who do conceive, an increased likelihood of miscarriage. Obesity can affect reproduction through fat cell metabolism, steroids and secretion of proteins such as leptin and adiponectin and through changes induced at the level of important homeostatic factors such as pancreatic secretion of insulin, androgen synthesis by the ovary and sex hormone-binding globulin (SHBG) production by the liver. WHO estimates that 9 to 25% of women in developed countries are severely obese, and obese mothers are much more likely to have obese children, especially if they have gestational diabetes. Obesity-associated anovulation may lead to infertility and to a higher risk of miscarriage. Management of anovulation with obesity involves diet and exercise as well as standard approaches to ovulation induction. Many obese women conceive without assistance, but pregnancies in obese women have increased rates of pregnancy-associated hypertension, gestational diabetes, large babies, Cesarean section and perinatal mortality and morbidity. Among contraceptors, the fear of weight gain affects uptake and continuation of hormonal contraceptives, although existing trials indicate that any such effects are small. For all methods of hormonal contraception, weight above 70 kg is associated with increased failure rates.

  8. Circadian Rhythms and Clock Genes in Reproduction: Insights From Behavior and the Female Rabbit’s Brain

    Directory of Open Access Journals (Sweden)

    Mario Caba

    2018-03-01

    Full Text Available Clock gene oscillations are necessary for a successful pregnancy and parturition, but little is known about their function during lactation, a period demanding from the mother multiple physiological and behavioral adaptations to fulfill the requirements of the offspring. First, we will focus on circadian rhythms and clock genes in reproductive tissues mainly in rodents. Disruption of circadian rhythms or proper rhythmic oscillations of clock genes provoke reproductive problems, as found in clock gene knockout mice. Then, we will focus mainly on the rabbit doe as this mammal nurses the young just once a day with circadian periodicity. This daily event synchronizes the behavior and the activity of specific brain regions critical for reproductive neuroendocrinology and maternal behavior, like the preoptic area. This region shows strong rhythms of the PER1 protein (product of the Per1 clock gene associated with circadian nursing. Additionally, neuroendocrine cells related to milk production and ejections are also synchronized to daily nursing. A threshold of suckling is necessary to entrain once a day nursing; this process is independent of milk output as even virgin does (behaving maternally following anosmia can display circadian nursing behavior. A timing motivational mechanism may regulate such behavior as mesolimbic dopaminergic cells are entrained by daily nursing. Finally, we will explore about the clinical importance of circadian rhythms. Indeed, women in chronic shift-work schedules show problems in their menstrual cycles and pregnancies and also have a high risk of preterm delivery, making this an important field of translational research.

  9. Filial caregiving is associated with greater neuroendocrine dysfunction: Evidence from the 2005 National Survey of Midlife in the United States

    Directory of Open Access Journals (Sweden)

    SunWoo Kang

    2014-01-01

    Full Text Available Objectives: This study examined associations between providing caregiving for a biological or adoptive parent and clinically assessed biological risk factors (allostatic load and its three subscales—inflammatory dysfunction, metabolic dysfunction, and neuroendocrine dysfunction, as well as moderation of these associations by gender. Methods: Regression models were estimated using telephone and self-report data from 962 men and women who participated in the National Survey of Midlife in the United States in 2005. Results: Filial caregivers demonstrated higher levels of neuroendocrine dysfunction. No gender difference in biological risks was found. Discussion: Filial caregiving is the most prevalent form of family caregiving, and results indicating the presence of greater neuroendocrine dysfunction among filial caregivers in contrast to noncaregivers suggest an important public health concern. Future research needs to continue to examine different relationship types of caregivers and include a range of biological risk measurement to further the understanding of how family caregiving is linked to biological health risks.

  10. Neuroendocrine control of the onset of puberty.

    Science.gov (United States)

    Plant, Tony M

    2015-07-01

    This chapter is based on the Geoffrey Harris Memorial Lecture presented at the 8th International Congress of Neuroendocrinology, which was held in Sydney, August 2014. It provides the development of our understanding of the neuroendocrine control of puberty since Harris proposed in his 1955 monograph (Harris, 1955) that "a major factor responsible for puberty is an increased rate of release of pituitary gonadotrophin" and posited "that a neural (hypothalamic) stimulus, via the hypophysial portal vessels, may be involved." Emphasis is placed on the neurobiological mechanisms governing puberty in highly evolved primates, although an attempt is made to reverse translate a model for the timing of puberty in man and monkey to non-primate species. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Determinants of salivary cortisol levels in 10-12 year old children; a population-based study of individual differences

    NARCIS (Netherlands)

    Rosmalen, JGM; Oldehinkel, AJ; Ormel, J; de Winter, AF; Buitelaar, JK; Verhulst, FC

    The hypothalamic-pituitary-adrenal (HPA)-axis is a central component of the body's neuroendocrine response to stress. Its major end-product cortisol has profound effects on mood and behavior. Although it has often been suggested, it remains unknown whether differences in HPA-axis physiology are part

  12. Stress influencing production and welfare in farmed mink

    DEFF Research Database (Denmark)

    Malmkvist, Jens

    2012-01-01

    Results linking stress, production and welfare in farmed mink, with special focus on the hypothalamic-pituitary-adrenal (HPA)-axis, are presented. Interpretation of stress responses are discussed, combining context, neuroendocrine and behavioural indicators. Results from the development and valid......Results linking stress, production and welfare in farmed mink, with special focus on the hypothalamic-pituitary-adrenal (HPA)-axis, are presented. Interpretation of stress responses are discussed, combining context, neuroendocrine and behavioural indicators. Results from the development...... animals and whether fur-chewing/stereotypic behaviour is associated with hippocampal neurogenesis in mink. Perspectives and suggested future research aiming to improve production and welfare in farmed mink are given....

  13. Vulvar mucinous adenocarcinoma with neuroendocrine differentiation: A case report and review of the literature

    NARCIS (Netherlands)

    Rosmalen, M.H. Van; Reijnen, C.; Boll, D.; Pijnenborg, J.M.A.; Wurff, A.A. van der; Piek, J.M.

    2016-01-01

    BACKGROUND: There are limited cases in literature of patients with mucinous adenocarcinoma of the vulva with neuroendocrine differentiation have. With this new case, we aim to provide an overview of the existing literature and present a tool with relevant markers for the pathologist in the

  14. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner

    Directory of Open Access Journals (Sweden)

    Christina Göngrich

    2016-08-01

    Full Text Available Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36, the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG axis at the level of the anterior pituitary gland (AP. We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.

  15. 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...

  16. Estresse e função reprodutiva feminina Stress and female reproductive function

    Directory of Open Access Journals (Sweden)

    Simone da Nóbrega Tomaz Moreira

    2005-03-01

    Full Text Available Este artigo discute a relação do estresse sobre a função reprodutiva, considerando que a infertilidade pode ter causas psicológicas (hipótese da psicogênese ou pode ser a origem do estresse psicológico. A presença do estresse tem o potencial de ativar o eixo hipotálamo-hipófise-adrenal, o qual, inibe o eixo hipotálamo-hipófise-ovariano, levando à paralisação temporária das menstruações. Esse processo pode resultar em infertilidade transitória para as mulheres. Os autores enfatizam a necessidade de uma abordagem psicológica nos serviços de reprodução, objetivando trabalhar as tensões e frustrações advindas da infertilidade e do seu tratamento.This article discusses the relationship between stress and reproduction considering that infertility could bear psychological causes (psychogenesis hypothesis or could be caused by psychological stress. Stress has the potential of activating the hypothalamus-hypophisis-adrenal axis inhibiting the hypothalamus-hypophisis-ovarian axis leading to temporary menstruation paralysis. This process could result in a transitory infertility of women. The authors emphasize the need of a psychological approach in reproduction services with the objective of treating tensions and frustrations derived from infertility and its treatment.

  17. Neuroendocrine Disturbances after Brain Damage: An Important and Often Undiagnosed Disorder

    Directory of Open Access Journals (Sweden)

    Fatih Tanriverdi

    2015-04-01

    Full Text Available Traumatic brain injury (TBI is a common and significant public health problem all over the world. Until recently, TBI has been recognized as an uncommon cause of hypopituitarism. The studies conducted during the last 15 years revealed that TBI is a serious cause of hypopituitarism. Although the underlying pathophysiology has not yet been fully clarified, new data indicate that genetic predisposition, autoimmunity and neuroinflammatory changes may play a role in the development of hypopituitarism. Combative sports, including boxing and kickboxing, both of which are characterized by chronic repetitive head trauma, have been shown as new causes of neuroendocrine abnormalities, mainly hypopituitarism, for the first time during the last 10 years. Most patients with TBI-induced pituitary dysfunction remain undiagnosed and untreated because of the non-specific and subtle clinical manifestations of hypopituitarism. Replacement of the deficient hormones, of which GH is the commonest hormone lost, may not only reverse the clinical manifestations and neurocognitive dysfunction, but may also help posttraumatic disabled patients resistant to classical treatment who have undiagnosed hypopituitarism and GH deficiency in particular. Therefore, early diagnosis, which depends on the awareness of TBI as a cause of neuroendocrine abnormalities among the medical community, is crucially important.

  18. The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-β.

    Science.gov (United States)

    Adzic, Miroslav; Djordjevic, Jelena; Mitic, Milos; Brkic, Zeljka; Lukic, Iva; Radojcic, Marija

    2015-09-15

    Peripheral inflammation induced by lipopolysaccharide (LPS) causes behavioural changes indicative for depression. The possible mechanisms involve the interference with neuroinflammatory, neuroendocrine, and neurotrophic processes. Apart from heterogeneity in the molecular background, sexual context may be another factor relevant to the manifestation of mood disturbances upon an immune challenge. We investigated sex-dependent effects of a 7-day LPS treatment of adult Wistar rats on depressive-like behaviour and their relation with hypothalamic neuroendocrine factor, corticotrophin-releasing hormone (CRH), proplastic brain-derived neurotropic factor (BDNF), pro-inflammatory cyclooxygenase-2 (COX-2) and nuclear factor kappa beta (NFkB). Also, their regulators, the glucocorticoid receptor (GR) and CCAAT enhancer-binding protein (C/EBP) β were followed. LPS induced depressive-like behaviour in females was associated with the increased hypothalamic CRH and decreased BDNF, but not with COX-2. These changes were paralleled by an increase in nuclear GR, NFkB and 20 kDa C/EBPβ. LPS also altered behaviour in males and increased CRH expression, but in contrast to females, this was accompanied with the elevated COX-2, accumulation of cytosolic GR and elevated nuclear 38 kDa C/EBPβ and NFkB. In conclusion, depressive-like phenotype induced by LPS in both sexes emerges from similar HPA axis activation and sex-specific alterations of hypothalamic molecular signalling: in males it is related to compromised control of neuroinflamation connected with cytoplasmic GR retention, while in females it is related to diminished proplastic capacity of BDNF. Sex-dependent mechanisms by which inflammation alters hypothalamic processes and cause pathological behaviour in animals, could be operative in the treatment of depression-related brain inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Reproductive rights approach to reproductive health in developing countries

    Directory of Open Access Journals (Sweden)

    Vijayan K. Pillai

    2011-12-01

    Full Text Available Research on reproductive health in developing countries focuses mostly on the role of economic development on various components of reproductive health. Cross-sectional and empirical research studies in particular on the effects of non-economic factors such as reproductive rights remain few and far between.This study investigates the influence of two components of an empowerment strategy, gender equality, and reproductive rights on women's reproductive health in developing countries. The empowerment strategy for improving reproductive health is theoretically situated on a number of background factors such as economic and social development.Cross-national socioeconomic and demographic data from a number of international organizations on 142 developing countries are used to test a model of reproductive rights and reproductive health.The findings suggest that both economic and democratic development have significant positive effects on levels of gender equality. The level of social development plays a prominent role in promoting reproductive rights. It is found that reproductive rights channel the influences of social structural factors and gender equality on reproductive health.

  20. Reproductive rights approach to reproductive health in developing countries.

    Science.gov (United States)

    Pillai, Vijayan K; Gupta, Rashmi

    2011-01-01

    Research on reproductive health in developing countries focuses mostly on the role of economic development on various components of reproductive health. Cross-sectional and empirical research studies in particular on the effects of non-economic factors such as reproductive rights remain few and far between. This study investigates the influence of two components of an empowerment strategy, gender equality, and reproductive rights on women's reproductive health in developing countries. The empowerment strategy for improving reproductive health is theoretically situated on a number of background factors such as economic and social development. Cross-national socioeconomic and demographic data from a number of international organizations on 142 developing countries are used to test a model of reproductive rights and reproductive health. The findings suggest that both economic and democratic development have significant positive effects on levels of gender equality. The level of social development plays a prominent role in promoting reproductive rights. It is found that reproductive rights channel the influences of social structural factors and gender equality on reproductive health.