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: 4.93

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 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
Year

Additional details

5-year impact 3.63
Cited half-life 0.00
Immediacy index 1.33
Eigenfactor 0.01
Article influence 1.01
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

Karger

  • 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
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Depression is a serious condition that occurs more frequently in women and is often associated with treatment-resistance. The main hypotheses of this study were that (a) aldosterone is an early marker of depression onset and (b) tryptophan (TRP) depletion model of depression previously validated in male rats is treatment-resistant in females. To explore possible underlying mechanisms, we have focused on factors shown to be altered in patients with treatment-resistant depression. Female Sprague-Dawley rats were treated with a control or low TRP containing diet for various time periods up to 21 days. The results show that aldosterone secretion increased after 4 days of TRP depletion and prior to corticosterone. Optimal effects of TRP depletion occurred at 14 days. In addition to neurochemical and behavioural changes observed previously in males, TRP depletion in females was associated with significant decline in serum magnesium concentrations, increased serum interleukin-6, enhanced gene expression of orexin A in the frontal cortex and a rise in N-methyl-D-aspartate (NMDA) receptor Bmax in the amygdala. Depression-like behaviour, NMDA receptor upregulation, enhancement of the kynurenine to kynurenic acid ratio and magnesium were resistant to paroxetine treatment (10mg/kg/day in drinking water for 14 days). In conclusion, aldosterone may represent an important early marker for the onset of depression-like behaviour. With respect to treatment resistance, the underlying mechanisms may involve pro-inflammatory cytokines, kynurenine pathway, magnesium, glutamate neurotransmission and orexin pathway. This model of treatment-resistant depression may be useful for the future development of new compounds with novel antidepressant properties. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 05/2015; DOI:10.1159/000431152
  • [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the regulation of pubertal timing has relevance to developmental and human biology, and to the pathogenesis of various diseases. Recent large-scale genome-wide association studies for puberty timing and adult height, body mass index (BMI) and central body shape provide evidence for shared biological mechanisms that regulate these traits. There is substantial genetic overlap between age at menarche in women and BMI, with almost invariable directional consistency with the epidemiological associations between earlier menarche and higher BMI. By contrast, the genetic loci identified for age at menarche are largely distinct from those identified for central body shape, while alleles that confer earlier menarche can be associated with taller or shorter adult height. The findings of population-based studies for age at menarche show increasing relevance for other studies of rare monogenic disorders and enrich our understanding of the mechanisms that regulate the timing of puberty and reproductive function. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 05/2015; DOI:10.1159/000431023
  • [Show abstract] [Hide abstract]
    ABSTRACT: The semaphorin proteins, which contribute to the morphogenesis and homeostasis of a wide range of systems, are among the best-studied families of guidance cues. Much recent research has focused on the role of semaphorins in the development and adult activity of hormone systems, and reciprocally, how circulating reproductive hormones regulate their expression and function. Specifically, several reports have focused on the molecular mechanisms underlying the effects of semaphorins on the migration, survival and structural and functional plasticity of neurons that secrete gonadotropin-releasing hormone (GnRH), essential for the acquisition and maintenance of reproductive competence in mammals. Alterations in the development of this neuroendocrine system lead to anomalous or absent GnRH secretion, resulting in heterogeneous reproductive disorders such as congenital hypogonadotropic hypogonadism or other conditions characterized by infertility or subfertility. This review summarizes current knowledge of the role of semaphorins and their receptors on the development, differentiation and plasticity of the GnRH system. In addition, the involvement of genetic deficits in semaphorin signaling in some forms of hypogonadotropic hypogonadism in humans is discussed. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 05/2015; DOI:10.1159/000431021
  • [Show abstract] [Hide abstract]
    ABSTRACT: Non functioning pituitary adenomas (NFPA) account for about 40% of pituitary tumors. Pituitary deficiencies are present at diagnosis in 60-80% of NFPA and, classically, GH secretion is firstly lost while ACTH is expected to disappear at last. Aim of the study was to evaluate the incidence of multiple or isolated pituitary deficiencies in a large series of NFPA. We retrospectively analyzed data of 218 NFPA (59% females, 59% macroadenomas, average age: 50.2 ± 17 years) followed at our center from 1990 to 2013. At diagnosis all patients had a complete evaluation of pituitary function in basal conditions and provocative tests for hypotalamic-pituitary-adrenal axis, while tests for GH deficiency were carried out in 38%. 52.3% of patients (65.6% of macroadenomas, 33.3% of microadenomas) presented at least one pituitary deficiency: isolated deficiency in 29.8%, multiple deficiencies in 30% and panhypopitutiarism in 9%. Isolated deficiencies were hypogonadism in 11.5% of patients (8% in micro, 14% in macro), hypoadrenalism in 10.1% (14% in micro, 7% in macro) and GH deficiency in 8.3% (8.9% in micro, 7.8% in macro). About 30% of microadenomas had at least one pituitary deficiency at diagnosis, independently of tumor localization within the sellar region. The presence of isolated hypoadrenalism suggests that the order of appearance of hypopituitarism does not always follow the one expected. Given the relative high prevalence of isolated hypoadrenalism even in microadenomas, we suggest the full assessment of basal and dynamic pituitary function in all NFPA regardless of tumor size. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 04/2015; DOI:10.1159/000430815
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with active acromegaly are frequently insulin resistant, glucose intolerant and at risk for developing overt type 2 diabetes (T2DM). At the same time, these patients have a relatively lean phenotype associated mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the GH producing adenoma. Mouse models of acromegaly share many of these characteristics including a lean phenotype and proneness to T2DM. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as with the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 04/2015; DOI:10.1159/000430819
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alkylating agents, such as streptozocin and dacarbazine, have been reported as active in neuroendocrine neoplasms (NENs). Temozolomide (TMZ) is an oral, potentially less toxic derivative of dacarbazine, which has shown activity both as a single agent and in combination with other drugs. Nevertheless, its role in NENs has not been well defined. Several retrospective and prospective phase I-II studies have been published describing its use in a variety of NENs. The combination of capecitabine and TMZ was reported to be associated with a particularly high tumor response in pancreatic NENs as a first-line treatment, in a retrospective series. Although in NENs determination of O6-methylguanil-DNAmethyltransferase (MGMT) status has been suggested as a predictive biomarker of response, its role remains still investigational awaiting validation along with establishment of the optimal detection method. Metronomic schedules have been reported to potentially overcome MGMT-related drug resistance. Toxicity is manageable if well monitored. We reviewed the literature regarding pharmacological and clinical aspects of TMZ, focusing on specific settings of NENs, different schedules, toxicity and safety profile, and potential predictive biomarkers of response. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 04/2015; DOI:10.1159/000430816
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gonadotropin-releasing hormone (GnRH) neurons play a pivotal role in regulation of the hypothalamic-pituitary gonadal axis in a sex-specific manner. We hypothesized that the differences seen in reproductive functions of males and females are associated with a sexually dimorphic gene expression profile of GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact, metestrous female and male GnRH-GFP transgenic mice. About 1,500 individual GnRH neurons from each sex were sampled with laser capture microdissection followed by whole transcriptome amplification for gene expression profiling. Under stringent selection criteria (fold change >1.6, adjusted p value 0.01), Affymetrix Mouse Genome 430 PM array analysis identified 543 differentially expressed genes. Sexual dimorphism was most apparent in gene clusters associated with synaptic communication, signal transduction, cell adhesion, vesicular transport and cell metabolism. To validate microarray results, 57 genes were selected and 91% of their differential expression was confirmed by real-time PCR. Similarly, 88% of microarray results were confirmed with PCR from independent samples obtained by patch pipette harvesting and pooling of 30 GnRH neurons from each sex. We found significant differences in expression of genes involved in vesicle priming and docking (Syt1, Cplx1), GABAergic (Gabra3, Gabrb3, Gabrg2) and glutamatergic (Gria1, Grin1, Slc17a6) neurotransmission, peptide signaling (Sstr3, Npr2, Cxcr4) and the regulation of intracellular ion homeostasis (Cacna1, Cacnb1, Cacng5, Kcnq2, Kcnc1). The striking sexual dimorphism of the GnRH neuron transcriptome we report here contributes to the better understanding the differences in cellular mechanisms of GnRH neurons in the two sexes. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 04/2015; DOI:10.1159/000430818
  • [Show abstract] [Hide abstract]
    ABSTRACT: Male and female rats differ in their ability to utilize spinal endomorphin 2 (EM2, the predominant mu-opioid receptor ligand in spinal cord) and in the mechanisms that underlie spinal EM2 analgesic responsiveness. We investigated the relevance of spinal estrogen receptors (ERs) to the in vivo regulation of spinal EM2 release. ER antagonists were administered directly to the lumbosacral spinal cord of male and female rats, intrathecal perfusate was collected, and resulting changes in EM2 release were quantified using a plate-based radioimmunoassay. Intrathecal application of an antagonist of either estrogen receptor alpha (ERα) or the estrogen receptor GPR30 failed to alter spinal EM2 release. Strikingly, however, the concomitant blockade of ERα and GPR30 enhanced spinal EM2 release. This effect was sexually dimorphic, being absent in males. Furthermore, the magnitude of the enhancement of spinal EM2 release in females was dependent upon estrous cycle stage, suggesting a relationship with circulating levels of 17β-estradiol. The rapid onset of enhanced EM2 release following intrathecal application of ERα/GPR30 antagonists (within 30-40 min) suggests mediation via ERs in the plasma membrane, not the nucleus. Notably, both ovarian and spinally synthesized estrogens are essential for membrane ER regulation of spinal EM2 release. These findings underscore the importance of estrogens to the regulation of spinal EM2 activity and, by extension, endogenous spinal EM2 antinociception in females. Components of the spinal estrogenic mechanism(s) that suppress EM2 release could represent novel drug targets for improving utilization of endogenous spinal EM2, and thereby pain management in women. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 04/2015; DOI:10.1159/000430817
  • [Show abstract] [Hide abstract]
    ABSTRACT: Carcinoid heart disease (CHD) is a rare cardiac manifestation occurring in patients with advanced neuroendocrine tumors and the carcinoid syndrome, usually involving the right sided heart valves and eventually leading to right heart failure (RHF). The pathophysiology of CHD is still obscure and believed to be multifactorial, as a variety of vaso-active substances secreted by the tumour appear to be involved. The management of patients with CHD is complex, as both the systemic malignant disease and the heart involvement have to be addressed. Timely diagnosis and early surgical treatment in appropriately selected patients are of outmost importance, as CHD is associated with increased morbidity and mortality. Valve replacement surgery alleviates RHF and may also contribute to improved survival. In the present manuscript we have comprehensively reviewed the existing literature to date, mainly focusing on the pathophysiology of CHD; other aspects of CHD (such as the clinical presentation, the diagnostic tools and the therapeutic approach) are addressed in brief. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 04/2015; DOI:10.1159/000381930
  • [Show abstract] [Hide abstract]
    ABSTRACT: The phase III placebo-controlled RADIANT-2 trial investigated the efficacy of everolimus plus octreotide long-acting repeatable (LAR) in patients with advanced neuroendocrine tumors (NET) associated with carcinoid syndrome. Here we report a secondary analysis based on the previous somatostatin analogue (SSA) exposure status of patients enrolled in RADIANT-2. Patients were randomly assigned to receive oral everolimus 10 mg/day plus octreotide LAR 30 mg intramuscularly (i.m.) or to receive matching placebo plus octreotide LAR 30 mg i.m. every 28 days. SSA treatment before study enrollment was permitted. Patient characteristics and progression-free survival (PFS) were analyzed by treatment arm and previous SSA exposure status. Of the 429 patients enrolled in RADIANT-2, 339 were previously exposed to SSA (95% received octreotide); 173 of 339 patients were in the everolimus plus octreotide LAR arm. All patients had a protocol-specified history of secretory symptoms, but analysis by type showed that more patients who previously received SSA therapy had a history of flushing symptoms (77%), diarrhea (86%), or both (63%) compared with SSA-naive patients (62, 62 and 24%, respectively). Patients who received everolimus plus octreotide LAR had longer median PFS regardless of previous SSA exposure (with: PFS 14.3 months, 95% confidence interval [CI], 12.0-20.1; without: 25.2 months, 95% CI, 12.0-not reached) compared with patients who received placebo plus octreotide LAR (with: 11.1 months, 95% CI, 8.4-14.6; without: 13.6 months, 95% CI, 8.2-22.7). Everolimus in combination with octreotide improves PFS in patients with advanced NET associated with carcinoid syndrome, regardless of previous SSA exposure. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381715
  • [Show abstract] [Hide abstract]
    ABSTRACT: An association between neuroendocrine tumours (NET) and increased risk of developing second primary malignancies (SPM) has been recognised. Retrospective review of our institutional prospectively-maintained database of NET patients. We identified patients who had been diagnosed with both neuroendocrine and any additional malignancies via examination of patient notes. Clinical data for 169 patients were analysed. After exclusion of patients known to have hereditary tumour predisposition syndromes, 29 SPM were identified in 26 patients (15.38%), the commonest being colorectal (n = 6), breast and renal carcinomas (both n = 5). SPM were classified as previous, synchronous or subsequent relative to NET diagnosis. Rates of SPM in pancreatic and small-bowel NET patients were comparable (15.7% vs. 19.6%, p = 0.78). A person-year methodology was used to compare observed numbers of SPM against expected values generated from age- and sex-specific incidence tables, with standardised incidence ratios (SIRs) and 95% confidence intervals (CI) calculated. SPM incidence was significantly elevated in the synchronous sub-set (SIR 2.732, CI 1.177-5.382) whilst significantly fewer NET patients had a cancer history compared to the general population (SIR 0.4, CI 0.241-0.624). No overall differences were evident between observed and expected incidences of subsequent SPM (SIR 0.36, CI 0.044-1.051). The incidence of synchronous colorectal cancers was markedly elevated (SIR 13.079, CI 4.238-30.474). Our data support the use of colonoscopy in the diagnostic work-up of NET patients in anticipation of a colorectal SPM. The mechanistic underpinnings of this clinical phenomenon require further genetic investigation, and consideration of this knowledge in patient management pathways is warranted. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381716
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acromegaly is an insidious neuroendocrine disorder caused by hypersecretion of growth hormone (GH) by a somatotroph adenoma. Somatostatin receptor ligands (SRLs) are recommended as first-line medical therapy in patients for whom surgery has failed or is contraindicated. There are five known somatostatin receptor subtypes (SSTRs), two of which, SSTR2 and SSTR5, are expressed by a majority of somatotroph adenomas. The currently available SRLs, octreotide and lanreotide, primarily bind to SSTR2. Pasireotide (SOM230) is a new multi-receptor targeted SRL which has a broader binding profile and increased affinity for SSTR1, 2, 3 and 5. PubMed searches were performed to identify all of the available published English language data on pasireotide with regard mechanism of action, in vitro effects, and clinical data. Preclinical studies have demonstrated that pasireotide has a broader range of functional activity than octreotide. Recently, pasireotide's efficacy in attenuating GH and IGF-1 levels in patients with acromegaly has been evaluated in Phase III clinical trials. Pasireotide demonstrated superiority over octreotide in achieving biochemical control (ie, GH ≤2.5 µg/l and age- and sex-matched IGF-1 normalization) in patients with acromegaly, as well as significant efficacy in treating patients who were previously inadequately controlled on the maximum allowed doses of octreotide and lanreotide. Pasireotide-induced hyperglycemia was the most concerning adverse event, which was reversible upon discontinuation of pasireotide. The clinical data support pasireotide as a promising new therapy for treating acromegaly and the long-acting formulation recently was approved in the U.S and Europe for the treatment of acromegaly. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381460
  • [Show abstract] [Hide abstract]
    ABSTRACT: To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 atypical (3 with lymph node metastasis). The results were validated by means of real-time PCR in 37 carcinoids, including 22 typical (4 with lymph node metastasis) and 15 atypical (7 with lymph node metastasis), and 19 high grade neuroendocrine carcinomas. Unsupervised cluster analysis segregated the pilot cases in three distinct groups. Twenty-four microRNAs were differentially regulated in atypical versus typical carcinoids, and 29 in metastatic versus non-metastatic cases. Eleven microRNAs were selected for validation. All but one were significantly different among lung neuroendocrine tumor histotypes. Moreover, five (miR-129-5p, miR-409-3p, miR-409-5p, miR-185, miR-497) were significantly up-regulated in typical as compared to atypical carcinoids. MiR-409-3p, miR-409-5p and miR-431-5p were also significantly down-regulated in carcinoids metastatic to the lymph nodes. Predictive in silico analysis of specific target genes showed that these three latter miRNAs linked to metastatic potential are implicated in several cellular functions, and highlighted several novel genes which may be worthy exploring. Our findings demonstrate that lung carcinoids have distinct microRNA expression profiles as compared to high grade neuroendocrine carcinomas and that specific microRNAs might have potential implications as diagnostic tools or clinical biomarkers. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381454
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-Octreotide (TOC) and (123)I-mIBG in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography (CT) and establish an optimal imaging diagnostic algorithm in SDHx-mutation carriers. All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and (123)I-mIBG. Lesions were classified by body regions: head and neck (HN), chest, abdomen with pelvis, adrenal gland and metastasis. We evaluated 46 SDHx gene-mutation carriers (32 index cases, 14 relatives; 28 SDHD, 16 SDHB, 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients and malignant disease was diagnosed in 7 patients. In benign tumors, sensitivity of SRS was estimated at 77% and (123)I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region-dependent (P<0.001). The highest SRS sensitivity was found in HNP (91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40%, 42.9%). The highest (123)I-mIBG sensitivity was found in pheochromocytomas (sensitivity 100%) and the lowest in HNP (sensitivity 3.7%). In metastatic disease SRS was superior to mIBG (sensitivity 95.2 vs. 23.8%, respectively). SRS and (123)I-mIBG SPECT sensitivity in SDHx patients is highly body region-dependent. In malignant tumors SRS is superior to (123)I-mIBG SPECT. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381458
  • [Show abstract] [Hide abstract]
    ABSTRACT: BDNF is strongly related to hormonal networks and is modulated by hypothalamic activity. To evaluate plasma BDNF concentration in patients with Functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm and to assess whether the duration of amenorrhea might influence the BDNF/F ratio in FHA. Observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Basal values of BDNF and hormones were examined in blood samples collected from 7.00 a.m. to 9.00 a.m. in all of the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8.00, 12.00, 16.00, 20.00, and 24.00. BDNF plasma levels are significantly lower in amenorrheic women (p < 0.001) than in the follicular phase of eumenorrhoic women. There are no correlations between BDNF values (p > 0.05) sex steroids and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated to duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower if compared to the control group and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381456
  • [Show abstract] [Hide abstract]
    ABSTRACT: Kisspeptin (KP) was recently discovered as a potent stimulator of gonadotropin-releasing-hormone (GnRH) secretion and thereby a major regulator of the neuroendocrine-reproductive axis. KP signals via its cognate receptor (KISS1R), a G-protein-coupled receptor (GPCR) which activates the G-proteins Gαq/11. Modulation of KP interaction with KISS1R is therefore a potential new therapeutic target for stimulating (in infertility) or inhibiting (in hormone-dependent diseases) the reproductive hormone cascade. Major efforts are underway in targeting KISS1R in the treatment of sex steroid hormone-dependent disorders and in the stimulation of endogenous hormonal responses along the neuroendocrine axis as part of in vitro fertilization protocols. The development of analogs modulating KISS1R signaling will be aided by understanding the intracellular pathways and dynamics of KISS1R signaling under normal and pathological conditions. This review focuses on KISS1R recruitment of intracellular signaling pathways which mediate GnRH secretion and the dynamics of KISS1R expression at the cell surface. In addition to coupling to and signaling by Gαq/11, KISS1R couples to β-arrestin and both pathways mediate KP-dependent GnRH secretion. The review also considers factors such as KP concentration and the respective roles of rapid desensitization, internalization and recycling of re-sensitized receptors to the cell surface in maintaining an active and dynamic population of KISS1R at the cell surface to facilitate prolonged KP signaling. These findings highlight the potential for the utilization of KP and analogs in stimulating and inhibiting the reproductive hormone cascade as an alternative to targeting the downstream GnRH receptor. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; DOI:10.1159/000381457