Neuroendocrinology (Neuroendocrinology)

Publisher: Karger

Journal description

ëNeuroendocrinologyí publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immune cells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of coping behavior or clinical neuroendocrinology. Readers will also benefit from occasional, well-referenced reviews by noted experts which highlight especially active areas of current research.

Current impact factor: 4.37

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 4.373
2013 Impact Factor 4.934
2012 Impact Factor 3.537
2011 Impact Factor 2.376
2010 Impact Factor 3.272
2009 Impact Factor 3.074
2008 Impact Factor 2.913
2007 Impact Factor 2.295
2006 Impact Factor 2.68
2005 Impact Factor 2.65
2004 Impact Factor 2.509
2003 Impact Factor 2.844
2002 Impact Factor 2.511
2001 Impact Factor 2.144
2000 Impact Factor 2.744
1999 Impact Factor 3.214
1998 Impact Factor 3
1997 Impact Factor 2.441
1996 Impact Factor 2.445
1995 Impact Factor 2.684
1994 Impact Factor 2.422
1993 Impact Factor 2.702
1992 Impact Factor 2.841

Impact factor over time

Impact factor

Additional details

5-year impact 3.62
Cited half-life >10.0
Immediacy index 0.26
Eigenfactor 0.01
Article influence 1.07
Website Neuroendocrinology website
Other titles Neuroendocrinology (Online)
ISSN 1423-0194
OCLC 44647673
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author's server or institutional server
    • Server must be non-commercial
    • Publisher's version/PDF cannot be used
    • Publisher copyright and source must be acknowledged
    • Must link to publisher version
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/aims: Less than half of depression patients are correctly diagnosed within the primary care setting. Previous proteomic studies have identified numerous immune and neuroendocrine changes in patients. However, few studies have considered the joint effects of biological molecules and their diagnostic potential. Our aim was to develop and validate a diagnostic serum biomarker panel identified through joint effects analysis of multiplex immunoassay profiling data from 1,007 clinical samples. Methods: In stage 1, we conducted a meta-analysis of two independent cohorts of 78 first/recent onset drug-naive/drug-free depression patients and 156 controls and applied the 10-fold cross-validation with least absolute shrinkage and selection operator regression to identify an optimal diagnostic prediction model (biomarker panel). In stage 2, we tested the discriminatory performance of this biomarker panel using the naturalistic Netherlands Study of Depression and Anxiety (NESDA) cohort of 468 depression patients and 305 controls. Results: An optimal panel of 33 immune-neuroendocrine biomarkers and gender was selected in the meta-analysis. Testing this biomarker-gender panel using the NESDA cohort resulted in a moderate to good performance to differentiate patients from controls (0.69 < AUC< 0.86), particularly the first-episode patients free of chronic non-psychiatric diseases or medications and following incorporation of sociodemographic covariates (0.76 < AUC < 0.92). Conclusion: Despite the need for additional validation studies, we demonstrated that a blood-based biomarker-sociodemographic panel can detect depression in naturalistic healthcare settings with good discriminatory power. Further refinements of blood biomarker panels aiding in the diagnosis of depression may provide a cost-effective means to increase accuracy of clinical diagnosis within the primary care setting.
    Neuroendocrinology 11/2015; DOI:10.1159/000442208
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    ABSTRACT: Background/aims: Photoperiod is a major environmental cue in temperate zone birds which synchronizes breeding with the time of year that offers the optimal environment for offspring survival. Despite continued long photoperiods, these birds eventually become refractory to the stimulating photoperiod and their reproductive systems regress. In this study, we characterized the role of GABAergic neurotransmission in modulating the response of the premammillary nucleus (PMM) to a gonad stimulatory photoperiod and the onset of photorefractoriness. Methods and results: Bilateral ablation of the PMM blocked the light-induced neuroendocrine response from occurring in photosensitive turkeys. Microarray analyses revealed an increase in GABAergic activity in the PMM of photorefractory birds as opposed to photosensitive ones and this enhanced GABAergic activity appeared to inhibit the photoperiodic signal. Additionally, GABAA and GABAB receptors were expressed by dopamine-melatonin neurones in the PMM and the administration of GABA receptor agonist, baclofen, blocked the photoperiodic reproductive neuroendocrine responses. Conclusions: Consistent with the present findings, we propose that the long-sought-after mechanism underlying photorefractoriness is linked to the inhibitory actions of GABA. We suggest that (1) GABAergic interference with photoperiodic entrainment in the PMM initiates the photorefractory state and terminates the annual breeding season in temperate zone birds and (2) the PMM is a site of photoreception and photorefractoriness that controls the initiation and termination of avian reproductive seasonality.
    Neuroendocrinology 11/2015; DOI:10.1159/000442206
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    ABSTRACT: Background: Epidemiological studies show an increasing trend in the incidence of neuroendocrine neoplasms (NENs). A significant number of NENs occur in less common primary sites, but they are often excluded from the population-based studies. We studied the incidence trends of all NENs in Norway according to different primary sites. Materials and methods: Our analyses were based on cancer cases diagnosed between 1993 and 2010 and reported to the national population-based Cancer Registry of Norway. A total of 65 morphological codes were identified as neuroendocrine and stratified into 3 different groups of aggressiveness; low, intermediate and high. Results: We identified 16,075 NENs of which 49.5% were in women. Median age at diagnosis was 65 years. The most common primary sites were the lung (48.1%) and the gastroenteropancreatic system (18.0%). Stage at diagnosis was local in 40.4% of the cases, regional in 17.5% and distant in 42.1%. The stage distribution was stable throughout the study period. Age standardized (European) incidence rate (per 100,000 person years) increased from 13.3 to 21.3 from 1993 to 2010 with an estimated annual increase of 5.1 in women and 2.1% in men. The increase was most pronounced for tumors of intermediate aggressiveness from 3.3 in 1993 to 7.3 in 2010. Largest annual increases were estimated for adrenal gland (8.8%), pancreas (6.9%) and lung (6.1%). Conclusion: The incidence of NENs increased. Most primary tumors were found in the lungs or in the gastroenteropancreatic system. The increase in incidence differed according to primary site, gender and tumor aggressiveness.
    Neuroendocrinology 11/2015; DOI:10.1159/000442207
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    ABSTRACT: In models of acute brain injury, progesterone improves recovery through several mechanisms including modulation of neuroinflammation. Secondary injury from neuroinflammation is a potential therapeutic target after intracerebral hemorrhage (ICH). For potential translation of progesterone as a clinical acute ICH therapeutic, the present study sought to define efficacy of exogenous progesterone administration in ICH-relevant experimental paradigms. Young and aged C57BL/6 male, female, and ovariectomized (OVX) mice underwent left intrastriatal collagenase (0.05-0.075 U) or autologous whole blood (35 μl) injection. Progesterone at varying doses (4-16 mg/kg) was administered at 2, 5, 24, 48, and 72 h after injury. Rotarod and Morris water maze latencies were measured on days 1-7 and days 28-31 after injury, respectively. Hematoma volume, brain water content (cerebral edema), complementary immunohistochemistry, multiplex cytokine arrays, and inflammatory proteins were assessed at pre-specified time points after injury. Progesterone (4 mg/kg) administration improved rotarod and water maze latencies (p < 0.01) and decreased cerebral edema (p < 0.05) and microglial proliferation and neuronal loss (p < 0.01) in young and aged male, young OVX, and aged female mice. Brain concentration of pro-inflammatory cytokines and toll-like receptor-associated proteins were also decreased after progesterone (4 mg/kg) treatment (p < 0.01). Progesterone-treated young female mice showed no detectable effects. Exogenous progesterone improved short- and long-term neurobehavioral recovery and modulated neuroinflammation in male and OVX mice after ICH. Future studies should validate these findings, and address timing and length of administration before translation to clinical trial.
    Neuroendocrinology 11/2015; DOI:10.1159/000442204
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    ABSTRACT: Background/aims: Despite the success in treating some cancers, the efficacy of the mTOR inhibitors, rapalogs, as anti-cancer therapeutics, has been limited. We undertook to examine the effects of Torin1, a second generation selective ATP-competitive mTOR inhibitor in non-functioning pituitary tumor cells. During characterization of the molecular mechanisms that mediate Torin1 actions, there seemed to be a rationale for combining it with rapalogs. Methods: Proliferation assays, flow cytometry and Western blotting were applied to assess the effects of Torin1, RAD001, and their combination on MtT/E pituitary cell line and human derived non-functioning pituitary tumor cells. Results: Combined long treatments of Torin1 and RAD001 induced a pronounced reduction in cell growth and viability of both MtT/E pituitary cell line and human derived non-functioning pituitary tumor cells, superior to each drug alone. This was remarkable in the 10 nM combination and was reflected in a triggered decrease of cyclin D3 and p21/CIP expression. Interestingly, Akt-Thr308 and SIN1-Thr86 phosphorylations were robustly elevated in the combined treatment, accompanied by a reduction of PTEN expression. Phosphorylation of p70S6K was abolished in all individual and combined treatments. Akt-Ser473 phosphorylation, induced by RAD001, was reduced by the combined treatment to the same extent as when treated by Torin1 alone. Conclusions: Our results suggest that the differential signaling mechanisms induced by these compounds eventually converge to lead to an efficient blockade of the PI3K/Akt/mTOR pathway in pituitary tumor cells and may facilitate a reduction in treatment dosage.
    Neuroendocrinology 11/2015; DOI:10.1159/000442205
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    ABSTRACT: The median eminence (ME) of the hypothalamus comprises the hypothalamic nerve terminals, glia (especially tanycytes) and the portal capillary vasculature that transports hypothalamic neurohormones to the anterior pituitary gland. The ultrastructure of the ME is dynamically regulated by hormones and undergoes organizational changes during development and reproductive cycles in adult females, but relatively little is known about the ME during aging, especially in non-human primates. Therefore, we used a novel transmission scanning electron microscopy (tSEM) technique to examine the cytoarchitecture of the ME of young and aged female rhesus macaques in a preclinical monkey model of menopausal hormone treatments. Rhesus macaques were ovariectomized and treated for 2 years with vehicle, estradiol, or estradiol + progesterone (E2 + P4). While the overall cytoarchitecture of the ME underwent relatively few changes with age and hormones, changes to some features of neural and glial components near the portal capillaries were observed. Specifically, large neuroterminal size was greater in aged compared to young adult animals, an effect that was mitigated or reversed by E2 alone but not E2 + P4 treatment. Overall glial size, and the density and tissue fraction of the largest subset of glia, were greater in aged monkeys, and in some cases reversed by E2 treatment. Mitochondrial size was decreased by E2, but not E2 + P4, only in aged macaques. These results contrast substantially with work in rodents, suggesting that the ME of aging macaques is less vulnerable to age-related disorganization, and that estradiol's effects in the monkey ME are age-specific.
    Neuroendocrinology 11/2015; DOI:10.1159/000442015
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    ABSTRACT: Background and aims: It is unknown whether tumoral somatostatin receptor subtype 2a (sst2a) immunohistochemistry (IHC) has additional value over somatostatin receptor scintigraphy (SRS) uptake using OctreoScan® in predicting response to peptide receptor radiotherapy using 177Lu-octreotate (PRRT) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Aims of the study were to: (1) establish the percentage of sst2a immunopositivity in GEP-NET samples of PRRT-treated patients, (2) determine the relationship between best GEP-NET response using RECIST 1.0 at one year to PRRT and tumoral sst2a IHC, and (3) compare characteristics of patients with sst2a IHC-negative and -positive tumors. Methods: All 73 consecutive patients were selected for PRRT based on a positive SRS. Radiological response was scored according to RECIST 1.0. Sst2a status was detected on tumor samples by IHC. Results: GEP-NET samples showed in 93% sst2a IHC-positivity. No statistically significant relationship was observed between in vitro sst2a expression and in vivo best GEP-NET response at one year to PRRT (p = 0.47). Sex, primary tumor site, disease stage, ENETS TNM classification, Ki-67 index, highest serum chromogranin-A (CgA) level, and highest neuron specific enolase level (NSE) were not significantly different between patients with negative and positive sst2a tumoral IHC with the exception of age at diagnosis (p = 0.007). Conclusions: Sst2a IHC on tumor samples has no additional value over SRS uptake using OctreoScan® in predicting tumor response after PRRT.
    Neuroendocrinology 11/2015; DOI:10.1159/000441604
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    ABSTRACT: Since the establishment of transsphenoidal microsurgery as the operative treatment of choice in most patients with acromegaly 40 years ago, a few novel technical developments have evolved. Their application, utility and efficacy will be briefly discussed in this review article based on an analysis of published results and the authors' personal experience. The endoscope was additionally used to search for residual tumour in locations which could not be visualized with the operating microscope. In many centers it has to date fully replaced the operating microscope. Extended endoscopic operations have hardly limits in respect to accessible pathology. Over all, results and complications reported from microsurgical and endoscopic series are comparable. Intraoperative magnetic resonance imaging is able to depict the completeness of tumour resection. While additional tumour resections are performed on the basis of intraoperative imaging in many patients, the improvement in the hormonal remission rate reported is less impressive. Neuronavigation uses imaging data to improve orientation for the surgeon and is certainly a major asset for the inexperienced. In high case load centers it is mainly appreciated in anatomical variants and reoperations. While the Doppler probe is a valuable and easily affordable gadget to avoid vascular arterial injury, intraoperative ultrasound imaging of tumour extension has a much poorer resolution than magnetic resonance imaging and is thus not widely implemented. The clinical value of intraoperative growth hormone measurements is controversially discussed. In summary, the application of modern technology has only led to a minor improvement of results but has widened the spectrum of accessible pathologies and increased the safety of the procedures for the patient. It is expected that the outcome will continue to improve as novel techniques and concepts are developed.
    Neuroendocrinology 11/2015; DOI:10.1159/000441980
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    ABSTRACT: Background/aims: Histone deacetylases (HDACs) modulate lysine acetylation on histones and are frequently deregulated in cancer. HDAC inhibitors with potent anti-tumour effects have been developed and are now being tested in clinical trials. The aim of this study was to investigate the effects of valproic acid (VPA), an inhibitor of class-I and class-IIa HDACs, on neuroendocrine tumour (NET) cell growth. Methods: Three NET cell lines, GOT1 (small intestinal), KRJ-I (small intestinal), and BON (pancreatic), were treated with VPA and examined with respect to cell viability, cell-cycle arrest, apoptosis, and global transcriptional response. Results: We found that VPA induced a dose-dependent growth inhibition of NET cells in vitro, which was mainly due to activation of extrinsic and intrinsic apoptotic pathways. VPA induced a major transcriptional response by altering the expression of 16x2012;19% of the protein-coding genes in NET cell lines. Pathway analysis allowed prediction of alterations in key regulatory pathways, e.g. activation of TGFβ1, FOXO3, p53 signalling, and inhibition of MYC signalling. Analysis of GOT1 xenografts showed reduced growth and reduced Ki67 index, as well as an increase in apoptosis and necrosis after VPA treatment. Conclusions: We found that VPA treatment has a cytotoxic effect on NET cells of intestinal and pancreatic origin. There are several mechanisms by which VPA kills NET cells, which suggests the possibility of combination therapy. We propose that epigenetic therapy with HDAC inhibitors should be evaluated further in patients with NET disease.
    Neuroendocrinology 10/2015; DOI:10.1159/000441849
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    ABSTRACT: Objective: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological, and biochemical features as well as treatment and prognosis. Design: Twenty-three patients with p-dSOM (9 duodenal, 12 pancreatic, 2 unknown primary tumour) were identified from our prospective neuroendocrine tumour (NET) database, and data according to the study aims were recorded. Results: Of the 9 patients with duodenal SOM the m/f ratio was 4/5. All males and one female had NF-1. Seven patients had stage 1A-B and 2 had stage 2B disease. The Ki-67 index was 1-5% (median 2%). Plasma somatostatin was elevated in patients with 2B disease. Of the 14 patients with pancreatic SOM or unknown primary tumour the m/f ratio was 2/12. One male had MEN-1. Five had stage 1A-2B and nine had stage 4. The Ki-67 index was 1-40% (median 7%). Plasma somatostatin was elevated in seven patients. Patients reported symptoms related to the somatostatinoma syndrome, but none fulfilled the criteria for a full syndrome. Primary tumour in the pancreas, metastatic disease at diagnosis and higher tumour grade were all associated with a significantly poorer survival. Conclusion: None of the patients with p-dSOM presented with the full somatostatinoma syndrome. Prognostic factors are localisation of the primary tumour, dissemination and tumour grade. A Ki-67 of 5% may discriminate the course of disease.
    Neuroendocrinology 10/2015; DOI:10.1159/000441605
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    ABSTRACT: Introduction: In patients with small intestinal neuroendocrine tumours (siNET), the surgical resection of the primary tumour and associated mesenteric lymph nodes (LN) is recommended but is not well standardized and can be risky in patients with superior mesenteric vessels involvement. We aimed to evaluate the correlation between the length of resected small bowel and the number of removed LN, and to propose a preoperative morphological classification of siNET-associated LN. Methods: Records of patients operated on for siNET at two expert centers between August 2005 and November 2013 were analyzed. Two specialist radiologists reviewed the preoperative imaging and classified mesenteric LN into 5 stages according to their proximity to the truck and/or branches of the superior mesenteric artery. Results: Seventy-two patients were included. The mean number of removed LN was 12 ± 15 and the length of removed small intestine 53 ± 43 cm. No correlation existed between the length of small bowel resection and the number of removed LN. Overall, 9 (12%), 13 (18%), 36 (50%), 14 (19%) and 0 patients were classified into LN-stage 0, I, II, III and IV. The correlation rate between the two observers was 0.98. Patients with LN-stage III (hardly resectable) had more removed LN than those with LN-stages 0, I or II (easily removable). Conclusion: An optimal lymphadenectomy is not always associated to an extended small bowel resection. In the era of small bowel-sparing surgery, the preoperative classification of mesenteric LN could help standardizing the surgical management of patients with siNET.
    Neuroendocrinology 10/2015; DOI:10.1159/000441423

  • Neuroendocrinology 09/2015; 102(3):181-183. DOI:10.1159/000441115
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    ABSTRACT: Background: Preclinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage (ICH); however, gonadal hormones have sex-specific effects. Therefore, an experimental model of ICH was used to assess recovery after progesterone administration in male and female rats. Methods: ICH was induced in male and female Wistar rats via stereotactic intrastriatal injection of clostridal collagenase (0.5 U). Animals were randomized to receive vehicle or 8 mg/kg progesterone intraperitoneally at 2 h, then subcutaneously at 5, 24, 48, and 72 h post-injury. Outcomes included relevant physiology during the first 3 h, hemorrhage and edema evolution over the first 24 h, pro-inflammatory transcription factor and cytokine regulation at 24 h, rotarod latency and neuroseverity score over the first 7 days, and microglial activation/macrophage recruitment at 7 days after injury. Results: Rotarod latency (p = 0.001) and neuroseverity score (p = 0.01) were improved in progesterone-treated males, but worsened in progesterone-treated females (p = 0.028 and p = 0.008, respectively). Progesterone decreased cerebral edema (p = 0.04), microglial activation/macrophage recruitment (p < 0.001), and pro-inflammatory transcription factor phosphorylated nuclear factor-kappaB p65 expression (p = 0.0038) in males but not females, independent of tumor necrosis factor-α, interleukin-6, and toll-like receptor-4 expression. Cerebral perfusion was increased in progesterone-treated males at 4 h (p = 0.043) but not 24 h after injury. Hemorrhage volume, arterial blood gases, glucose, and systolic blood pressure were not affected. Conclusions: Progesterone administration improved early neurobehavioral recovery and decreased secondary neuroinflammation after ICH in male rats. Paradoxically, progesterone worsened neurobehavioral recovery and did not modify neuroinflammation in female rats. Future work should isolate mechanisms of sex-specific progesterone effects after ICH.
    Neuroendocrinology 09/2015; DOI:10.1159/000440883
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    ABSTRACT: Background: Appendix goblet cell carcinoids (GCCs) are known to share histological features of adenocarcinoma and neuroendocrine tumours. Due to their low incidence, quality evidence is lacking for management of these patients. Methods: We performed a single-centre retrospective study of patients with confirmed diagnosis of appendiceal GCC (1996-2014). Patients were divided into curative intent (CI) and palliative intent (PI) cohorts. Our primary end-point was overall survival (OS). Results: Seventy-four patients were eligible; 76% were treated with CI (surgery only (36%), Cytoreductive Surgery (CRS) and Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) (36%), adjuvant chemotherapy (20%) and combination of CRS and HIPEC followed by adjuvant chemotherapy (9%)); 23% had advanced stage-disease amenable to palliative treatment (chemotherapy or supportive care) only. Completion right hemicolectomy, performed in 64% of the CI cohort, did not impact on relapse rate or disease-free survival. FOLFOX chemotherapy was used in both adjuvant and palliative settings; safety was as expected and we observed a high rate (60%) of disease control in the palliative cohort. The estimated median OS (all patients), disease-free (CI patients) and progression-free survivals (PI patients) were 52.1 (95% CI 29.4-90.3), 75.9 (26.6-not reached) and 5.3 (0.6-5.7) months, respectively. Age and stage were independent factors associated with OS in the multivariable analysis. Tang classification showed a trend for impact on OS. No benefit from specific adjuvant approach was identified; however selection bias for treatment approach was observed. Conclusion: Prospective trials are needed to define optimal approaches in GCC. All GCC patients should be managed by specialized centres due to their esoteric behaviour; we provide management considerations based on our experience and conclusions.
    Neuroendocrinology 09/2015; DOI:10.1159/000440725