Neuroendocrine System (neuroendocrine + system)

Distribution by Scientific Domains

Selected Abstracts

Anatomical Markers of Activity in Neuroendocrine Systems: Are we all ,Fos-ed out'?

G. E. Hoffman
Abstract It has now been nearly 15 years since the immediate early gene, c -fos, and its protein product, Fos, were introduced as tools for determining activity changes within neurones of the nervous system. In the ensuing years, this approach was applied to neuroendocrine study with success. With it have come advances in our understanding of which neuroendocrine neurones respond to various stimuli and how other central nervous system components interact with neuroendocrine neurones. Use of combined tract-tracing approaches, as well as double-labelling for Fos and transmitter markers, have added to characterization of neuroendocrine circuits. The delineation of the signal transduction cascades that induce Fos expression has led to establishment of the relationship between neurone firing and Fos expression. Importantly, we can now appreciate that Fos expression is often, but not always, associated with increased neuronal firing and vice versa. There are remaining gaps in our understanding of Fos in the nervous system. To date, knowledge of what Fos does after it is expressed is still limited. The transience of Fos expression after stimulation (especially if the stimulus is persistent) complicates design of experiments to assess the function of Fos and makes Fos of little value as a marker for long-term changes in neurone activity. In this regard, alternative approaches must be sought. Useful alternative approaches employed to date to monitor neuronal changes in activity include examination of (i) signal transduction intermediates (e.g. phosphorylated CREB); (ii) transcriptional/translational intermediates (e.g. heteronuclear RNA, messenger RNA (mRNA), prohormones); and (iii) receptor translocation. Another capitalizes on the fact that many neuroendocrine systems show striking stimulus-transcription coupling in the regulation of their transmitter or its synthetic enzymes. Together, as we move into the 21st Century, the use of multiple approaches to study activity within neuroendocrine systems will further our understanding of these important systems. [source]

New genomic avenues in behavioural neuroendocrinology ,

S. L. Lightman
Abstract Neuroendocrine systems play a key role not only in the maintenance of whole-body homeostasis but also as the link between behavioural, endocrine and autonomic responses to environmental stimuli. It is becoming increasingly clear that neuroendocrine regulatory mechanisms are under the control of a combination of factors including genetic background, environment and early-life programming. Patterns of gene expression are increasingly being used to provide information on the genotypes associated with particular behaviours, and modulation of specific parts of the genome allow investigation of the contribution of particular genes. The sequencing of the genome provides a unique opportunity to elucidate the genetic contribution to neuroendocrine and behavioural processes, and to investigate the interactions between genetic and environmental factors. Although drugs can be used to activate or inhibit neurotransmitters and receptors, they lack specificity. New technologies now permit the activation or inactivation of both neurotransmitters and receptors in specific areas of the brain for defined periods, including crucially important developmental windows when activation appears to have long-term consequences. The future challenges are to define the critical mechanisms through which the genetic constitution of an individual human or experimental animal interacts with environmental cues to result in altered physiological or even pathological behaviour and endocrine function. [source]

A peek inside the neurosecretory brain through Orthopedia lenses

Luca Del Giacco
Abstract The wealth of expression and functional data presented in this overview discloses the homeogene Orthopedia (Otp) as critical for the development of the hypothalamic neuroendocrine system of vertebrates. Specifically, the results depict the up-to-date portrait of the regulation and functions of Otp. The development of neuroendocrine nuclei relies on Otp from fish to mammals, as demonstrated for several peptide and hormone releasing neurons. Additionally, the activity of Otp is essential for the induction of the dopaminergic phenotype in the hypothalamus of vertebrates. Recent insights into the pathways required for Otp regulation have revealed the implication of the main extracellular signals acting during hypothalamic development. Alterations in these pathways are involved in several neuronal disorders, and the resultant downstream misregulation of Otp might impair the development of the hypothalamus, and be therefore responsible for the neuroendocrine dysfunctions that typify these diseases. Developmental Dynamics 237:2295,2303, 2008. © 2008 Wiley-Liss, Inc. [source]

Epidermal keratinocytes as the forefront of the sensory system

Mitsuhiro Denda
Abstract, Various sensors that respond to physical or chemical environmental factors have been identified in the peripheral nervous system. Some of them, which respond to mechanical stress, osmotic pressure, temperature and chemical stimuli (such as pH), are also expressed in epidermal keratinocytes. Neurotransmitters and their receptors, as well as receptors that regulate the neuroendocrine system of the skin, are also present in keratinocytes. Thus, broadly speaking, epidermal keratinocytes appear to be equipped with sensing systems similar to those of the peripheral and central nervous systems. It had long been considered that only nerve C-terminals in the epidermis play a role in skin surface perception. However, building on earlier work on skin receptors and new findings introduced here, we present in this review a novel hypothesis of skin sensory perception, i.e. first, keratinocytes recognize various environmental factors, and then the information is processed and conveyed to the nervous system. [source]

Molecular mechanisms of intercellular communication in the hormonal and neural systems

IUBMB LIFE, Issue 5-6 2006
Shigetada Nakanishi
Abstract This paper reviews our studies that have addressed the molecular mechanisms underlying the biosynthesis and reception of extracellular signaling molecules and integrative mechanisms of extracellular-intracellular signaling transmission in biological systems. We introduced recombinant DNA technology into the neuroendocrine system and established the concept that a single peptide precursor encompasses multiple biologically active peptides and brings about coordinate functions in various biological systems. We then developed a novel functional cloning of membrane receptors and ion channels by combining an oocyte expression system with electrophysiology. We molecularly elucidated not only various peptide receptors, including the first demonstration of the molecular entity of a G protein-coupled peptide receptor (GPCR), substance K receptor, and also diverse members of both G protein-coupled metabotropic type and NMDA type of neurotransmitter glutamate receptors. We demonstrated many novel synaptic mechanisms involving distinct types of glutamate receptors in brain function and dysfunction. These include the mechanisms underlying segregation of light-dark signals in visual transmission, discrimination and memory formation in olfactory transmission, and motor co-ordination in the cerebellum, basal ganglia and the retinal network. iubmb Life, 58: 349-357, 2006 [source]

Conservation of the function counts: homologous neurons express sequence-related neuropeptides that originate from different genes

Susanne Neupert
Abstract By means of single-cell matrix assisted laser desorption/ionization time-of-flight mass spectrometry, we analysed neuropeptide expression in all FXPRLamide/pheromone biosynthesis activating neuropeptide synthesizing neurons of the adult tobacco hawk moth, Manduca sexta. Mass spectra clearly suggest a completely identical processing of the pheromone biosynthesis activating neuropeptide-precursor in the mandibular, maxillary and labial neuromeres of the subesophageal ganglion. Only in the pban -neurons of the labial neuromere, products of two neuropeptide genes, namely the pban -gene and the capa -gene, were detected. Both of these genes expressed, amongst others, sequence-related neuropeptides (extended WFGPRLamides). We speculate that the expression of the two neuropeptide genes is a plesiomorph character typical of moths. A detailed examination of the neuroanatomy and the peptidome of the (two) pban -neurons in the labial neuromere of moths with homologous neurons of different insects indicates a strong conservation of the function of this neuroendocrine system. In other insects, however, the labial neurons either express products of the fxprl -gene or products of the capa -gene. The processing of the respective genes is reduced to extended WFGPRLamides in each case and yields a unique peptidome in the labial cells. Thus, sequence-related messenger molecules are always produced in these cells and it seems that the respective neurons recruited different neuropeptide genes for this motif. [source]

Interleukin-1, Release in the Supraoptic Nucleus Area During Osmotic Stimulation Requires Neural Function

J. Y. Summy-Long
Interleukin (IL)-1, is present throughout the magnocellular neuroendocrine system and co-depletes with oxytocin and vasopressin from the neural lobe during salt-loading. To examine whether IL-1, is released from the dendrites/soma of magnocellular neurones during osmotic stimulation, microdialysis adjacent to the supraoptic nucleus (SON) in conscious rats was combined with immunocapillary electrophoresis and laser-induced fluorescence detection to quantify cytokine in 5-min dialysates collected before (0,180 min; basal), and after (180,240 min), hypertonic saline injected s.c. (1.5 m NaCl). Osmotic release of IL-1, was compared after inhibiting local voltage-gated channels for Na+ (tetrodotoxin) and Ca2+ (cadmium and nickel) or by reducing intracellular Ca2+ stores (thapsigargin). Immunohistochemistry combined with microdialysis was used to localise cytokine sources (IL-1,+) and microglia (OX-42+). Under conditions of microdialysis, the basal release of IL-1,+ in the SON area was measurable and stable (pg/ml; mean ± SEM) from 0,60 min (2.2 ± 0.06), 60,120 min (2.32 ± 0.05) and 120,180 min (2.33 ± 0.06), likely originating locally from activated microglia (OX42+; IL-1,+; ameboid, hypertrophied) and magnocellular neurones expressing IL-1,. In response to osmotic stimulation, IL-1, increased progressively in dialysates of the SON area by a mechanism dependent on intracellular Ca2+ stores sensitive to thapsigargin and, similar to dendritic secretion of oxytocin and vasopressin, required local voltage-gated Na+ and Ca2+ channels for activation by osmoregulatory pathways from the forebrain. During osmotic stimulation, neurally dependent release of IL-1, in the SON area likely upregulates osmosensitive cation currents on magnocellular neurones (observed in vitro by others), to facilitate dendritic release of neurohypophysial hormones. [source]

Acupuncture in Polycystic Ovary Syndrome: Current Experimental and Clinical Evidence

E. Stener-Victorin
This review describes the aetiology and pathogenesis of polycystic ovary syndrome (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms related with PCOS. PCOS is the most common female endocrine disorder and it is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity. PCOS increases the risk for metabolic disturbances such as hyperinsulinaemia and insulin resistance, which can lead to type 2 diabetes, hypertension and an increased likelihood of developing cardiovascular risk factors and impaired mental health later in life. Despite extensive research, little is known about the aetiology of PCOS. The syndrome is associated with peripheral and central factors that influence sympathetic nerve activity. Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS. Many women with PCOS require prolonged treatment. Current pharmacological approaches are effective but have adverse effects. Therefore, nonpharmacological treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS via modulation of endogenous regulatory systems, including the sympathetic nervous system, the endocrine and the neuroendocrine system. Experimental observations in rat models of steroid-induced polycystic ovaries and clinical data from studies in women with PCOS suggest that acupuncture exert long-lasting beneficial effects on metabolic and endocrine systems and ovulation. [source]

Oestrogen Receptors, Receptor Variants and Oestrogen Actions in the Hypothalamic-Pituitary Axis

M. A. Shupnik
Abstract Information on oestrogen action has grown exponentially in the past decade, and recent studies have begun to define the mechanism of ligand-dependent activation and cell-specific effects. Oestrogen-mediated gene transcription in a specific tissue depends on several factors, the most important of which is the presence of at least one of the two nuclear oestrogen receptor (ER) isoforms, ER, and ER,. The presence and levels of specific ER isoform variants, along with receptor coactivator, corepressor and integrator proteins, directly modulate overall nuclear ER activity. The structure of the ligand, including both physiological oestrogens and synthetic oestrogen receptor modulators, influences ER interactions with these other proteins and thus determines the biological response. Furthermore, peptide and neurotransmitter-stimulated intracellular signalling pathways activate specific enzyme cascades and may modify the receptors and their interacting proteins, resulting in either independent or ligand-enhanced ER-mediated responses. Finally, several rapid effects of oestrogen probably occur at the membrane through nongenomic pathways that may or may not require the same ER proteins that are found in the nucleus. This review concentrates on the pituitary-hypothalamic axis and the genomic effects of oestrogen, and discusses the current knowledge of each of these factors in determining oestrogen actions in the neuroendocrine system. [source]

Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone Treatment

K. Felszeghy
Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 µg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 µg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source]

Hypothalamic Function in Response to 2-Deoxy- d -Glucose in Long-Term Abstinent Alcoholics

ALCOHOLISM, Issue 5 2001
John C. Umhau
Background: The body adapts to diverse stressful stimuli with a response characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Chronic alcohol consumption can cause changes in the function of this neuroendocrine system. Although many studies have examined this phenomenon in drinking and recently sober alcoholics, few studies have examined HPA axis function in long-term sober alcoholics. Methods: To characterize HPA axis function in long-term sober alcoholics, we used a challenge paradigm with 2-deoxy-d-glucose (2-DG). An infusion of 2-DG (a nonmetabolizable glucose analog) induces a well-characterized stress response. In a previous study, our laboratory found an exaggerated corticotropin and cortisol response in alcoholics abstinent 3 weeks; in this investigation we compared the effects of an infusion of 2-DG on 19 healthy volunteers and 20 community-living alcoholics who had been abstinent more than 6 months. Results: In contrast to the previous study, long-term sober alcoholics did not have an exaggerated corticotropin and cortisol response after 2-DG. Conclusions: Previously observed abnormalities in cortisol regulation in 3-week-sober alcoholics may be related to the acute effects of recent alcohol consumption and withdrawal. Future investigations into the metabolic function of alcoholics, particularly investigations involving the HPA system, should consider the possibility that normalization may not occur until long-term abstinence has been achieved. [source]

Transneuronal retrograde viral labeling in the brain stem and hypothalamus is more intense from the left than from the right adrenal gland,

Ida E. Tóth
Abstract Previous studies using the viral transneuronal tracing technique demonstrated central autonomic circuits involved in the innervation of the adrenal gland. Since increasing number of data indicate laterality in the neuroendocrine system, we aimed to investigate whether the supraspinal innervation of the adrenal gland exhibits asymmetry or not. The central circuitry involved in the innervation of the left and the right adrenal gland was studied in individual rats by dual transneuronal tracing using isogenic recombinant strains (Ba-DupGreen and Ba-Duplac expressing lacZ) of Bartha strain of pseudorabies virus. Viral infection of brain nuclei (dorsal vagal nucleus, nucleus of the solitary tract, caudal raphe nuclei, A5 cell group, hypothalamic paraventricular nucleus) from the left adrenal was more severe than that from the right organ. Dual-infected neurons were present both in the brain stem and in the hypothalamus. The results indicate a predominance in the supraspinal innervation of the left adrenal gland, and that each adrenal gland is innervated both by side-specific neurons and by neurons that project to both organs. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc. [source]

Six costs of immunity to gastrointestinal nematode infections

SUMMARY The strength of the immune response and the outcome of the interaction of a host with a parasite are influenced by genetic and phenotypic characteristics of both parties, and by environmental variables. Allocation of host resources to immune defence reduces resources available for other life-history traits. This review identifies six potential costs to the host from immune activation. The costs are likely to be broadly applicable to other immune responses in vertebrate species. Five phenotypic costs arise from: (i) increased metabolic activity; (ii) reduced nutrient availability due to anorexia; (iii) altered priorities for nutrient utilization; (iv) change in size and turnover of pools of immune cells and proteins; and (v) immunopathology from inappropriate or excessive immune activation. Subsumed by these costs is the cost of altered efficiency of nutrient use. A sixth cost is the genetic cost which arises from a change in the capacity of offspring to express production and life-history traits following selection for parasite resistance. The sensitivity of immune responses to the phenotypic status of the host, and the role the immune system shares with the neuroendocrine system in controlling use of resources underpin the importance of immunocompetence to the life-history of the host. [source]

The host,parasite neuroimmunoendocrine network in schistosomiasis: consequences to the host and the parasite

SUMMARY The physiological interactions during the course of any immune response are complex. Infection induces antigen-specific recognition by the immune system, which is consequently charged with the responsibility of marshalling the appropriate effector responses necessary to destroy the pathogen, or at the very least inhibit its progression. Obviously, the immune system should accomplish this while minimizing collateral damage to the host or it risks, winning a Pyrrhic victory. As our understanding of the neuroendocrine system grows, it has become increasingly clear that this complex network of neurotransmitters, hormones and cytokines plays an important role in mediating immunity. Schistosomes present an especially complex relationship between pathogen and these physiological systems, with hormonally dependent host factors such as sex and age correlated with parasite success. In this report, we review the current literature on sex and age associations between infection and progression of disease. We then follow with a discussion on interactions between the host neuroendocrine and immune systems. We also speculate on strategies to apply this knowledge to novel treatment strategies. Results argue for a complex network comprising the immune, endocrinological and nervous systems of both host and schistosome in the regulation of the plural outcomes of infection. [source]

Probing Pineal-specific Gene Expression with Transgenic Zebrafish,

Daisuke Kojima
The pineal gland of zebrafish (Danio rerio) contains light-sensitive photoreceptor cells and plays an important role in the neuroendocrine system. The zebrafish exorhodopsin gene encodes a pineal-specific photoreceptive protein, whose promoter region harbors a cis -acting element, pineal expression-promoting element (PIPE), directing pineal-specific gene expression. For in vivo genetic studies on PIPE-binding proteins and their regulatory mechanisms, we generated a transgenic zebrafish line, Tg(P20 -rh/P:gfp), that expresses green fluorescent protein (GFP) under the control of the zebrafish rhodopsin promoter fused with 20 PIPE repeats. In Tg(P20 -rh/P:gfp) fish, PIPE-dependent gene expression is visualized by GFP fluorescence in the pineal gland along with PIPE-independent GFP signals in the retinal rod photoreceptors. The transgenic fish exhibit detectable and reproducible GFP fluorescence in the larval pineal gland by 5 days postfertilization. Antisense morpholino-mediated knock-down of a pineal transcription factor gene, otx5, suppresses pineal GFP expression in the transgenic line. In a pilot screen of N -ethyl- N -nitrosourea-treated fish of the GFP transgenic line, we isolated potential dominant mutations that cause attenuation of pineal GFP fluorescence with a marginal effect on the retinal GFP signal. The results suggest that the Tg(P20 -rh/P:gfp) line will be useful for detecting deficits in PIPE-dependent gene expression in the pineal gland. [source]

Juvenile hormone,stimulated synthesis of acyl-glycerols and vitamin E in female accessory sexual glands of the fire bug, Pyrrhocoris apterus L.

Pavel Jedli
Abstract Secretory cells of the female accessory sexual glands (AG) of P. apterus grow and produce yellow oily exocrine secretion in response to stimulation by endogenous juvenile hormone (JH) or exogenous treatments by JH analogues. The secretion determines the property of future egg shells by coating the chorion surface of the oocytes that are passing individually through the common uterus during oviposition. Diapausing females with a physiologically inhibited endocrine system or females with artificially removed hormonal sources show inactive ovaries and empty AG without the secretory products. Ovary-ectomised females with the intact neuroendocrine system develop hypertrophic AG loaded with the oily secretion. This shows that there is no direct dependence between formation of the oily secretion in AG and ovarian growth. Chemical analysis of the secretory products revealed the presence of acetylated glycerols, with the most abundant stearoyl-diacetyl-glycerol, stearoyl-acetyl-propionyl-glycerol, and the corresponding derivatives of arachidonic acid. In addition to this, the JH-activated secretory cells of AG also produced , - and , -tocopherols. The possible antioxidant or antimutagenic action of these vitamin E compounds in insect reproduction has been emphasized. © 2009 Wiley Periodicals, Inc. [source]

The granin family of uniquely acidic proteins of the diffuse neuroendocrine system: comparative and functional aspects

Karen B. Helle
ABSTRACT The chromogranins A (CgA) and B (CgB) and secretogranin II (SgII) constitute the main members of a family of uniquely acidic secretory proteins in elements of the diffuse neuroendocrine system. These genetically distinct proteins, CgA, CgB, SgII and the less well known secretogranins III,VII are collectively referred to as,granins'and characterised by numerous pairs of basic amino acids as potential cleavage sites for processing by the co-stored prohormone converting enzymes PC 1/3 and PC2. This review is directed towards comparative and functional aspects of the granins with emphasis on their phylogenetically conserved sequences. Recent developments provide ample evidence of widely different effects and targets for the intact granins and their derived peptides, intracellularly in the directed trafficking of storage components during granule maturation and extracellularly in autocrine, paracrine and endocrine interactions. Most of the effects assigned to the granin derived peptides fit into patterns of direct or indirect inhibitory modulations of major functions. So far, peptides derived from CgA (vasostatins, chromacin, pancreastatin, WE-14, catestatin and parastatin), CgB (secretolytin) and SgII (secretoneurin) are the most likely candidates for granin-derived regulatory peptides, of postulated relevance not only for homeostatic processes, but also for tissue assembly and repair, inflammatory responses and the first line of defence against invading microorganisms. [source]

Expression of protein gene product 9·5 (PGP9·5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells

T. Otsuki
Summary The neuron cytoplasmic protein gene product 9·5 (PGP9·5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9·5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9·5 in myeloma cells was examined. PGP9·5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth-factor starvation, the upregulation of PGP9·5 was observed in association with that of p27Kip1, a cyclin-dependent-kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down-regulation of PGP9·5. These results suggested that PGP9·5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors. [source]

Evidence from immunoneutralization and antisense studies that the inhibitory actions of glucocorticoids on growth hormone release in vitro require annexin 1 (lipocortin 1)

A D Taylor
Our previous studies have identified a role for annexin 1 as a mediator of glucocorticoid action in the neuroendocrine system. The present study centred on growth hormone (GH) and exploited antisense and immunoneutralization strategies to examine in vitro the potential role of annexin 1 in effecting the regulatory actions of glucocorticoids on the secretion of this pituitary hormone. Rat anterior pituitary tissue responded in vitro to growth hormone releasing hormone, forskolin, 8-Bromo-cyclic adenosine 3,5,-monophosphate (8-Br-cyclic AMP) and an L-Ca2+ channel opener (BAY K8644) with concentration-dependent increases GH release which were readily inhibited by corticosterone and dexamethasone. The inhibitory actions of the steroids on GH release elicited by the above secretagogues were effectively reversed by an annexin 1 antisense oligodeoxynucleotide (ODN), but not by control (sense or scrambled) ODNs, as also were the glucocorticoid-induced increases in annexin 1. Similarly, a specific anti-annexin 1 monoclonal antibody quenched the corticosterone-induced suppression of secretagogue-evoked GH release while an isotype matched control antibody was without effect. Transmission electron micrographs showed that the integrity and ultrastructural morphology of the pituitary cells were well preserved at the end of the incubation and unaffected by exposure to the ODNs, antibodies, steroids or secretagogues. The results provide novel evidence for a role for annexin 1 as a mediator of the inhibitory actions of glucocorticoids on the secretion of GH by the anterior pituitary gland and suggest that its actions are effected at a point distal to the formation of cyclic AMP and Ca2+ entry. British Journal of Pharmacology (2000) 131, 1309,1316; doi:10.1038/sj.bjp.0703694 [source]

Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours

P. Ferolla
Summary The widespread availability and reliability of immunohistochemical techniques in the last three decades have allowed researchers to identify cells with common neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine cells form the so-called diffuse neuroendocrine system. Tumours arising from the cells of the diffuse neuroendocrine system are defined as (neuro)endocrine tumours (NETs). NETs have been increasingly described in recent years. However, despite the increase in the number of published papers focused on NET, we still lack adequate epidemiological data, particularly for non-gastroenteropancreatic (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for most sites is not completely known and is probably underestimated. As a consequence, data on the clinical features of many NET subgroups are not well known or confusing. For all of these reasons, we have attempted to evaluate the epidemiology of non-GEP NETs, reviewing the limited data available in the literature. [source]

Brain mechanisms underlying emotional alterations in the peripartum period in rats

Inga D. Neumann
Abstract In the period before and after parturition, i.e., in pregnancy and lactation, a variety of neuroendocrine alterations occur that are accompanied by marked behavioral changes, including emotional responsiveness to external challenging situations. On the one hand, activation of neuroendocrine systems (oxytocin, prolactin) ensures reproduction-related physiological processes, but in a synergistic manner also ensures accompanying behaviors necessary for the survival of the offspring. On the other hand, there is a dramatic reduction in the responsiveness of neuroendocrine systems to stimuli not relevant for reproduction, such as the hypothalamo-pituitary-adrenal (HPA) axis responses to physical or emotional stimuli in both pregnant and lactating rats. With CRH being the main regulator of the HPA axis, downregulation of the brain CRH system may result in various behavioral, in particular emotional, adaptations of the maternal organisms, including changes in anxiety-related behavior. In support of this, the lactating rat becomes less emotionally responsive to novel situations, demonstrating reduced anxiety, and shows a higher degree of aggressive behavior in the test for agonistic behavior as well as in the maternal defense test. These changes in emotionality are independent of the innate (pre-lactation) level of anxiety and are seen in both rats bred for high as well as low levels of anxiety. Both brain oxytocin and prolactin, highly activated at this time, play a significant role in these behavioral and possibly also neuroendocrine adaptations in the peripartum period. Depression and Anxiety 17:111,121, 2003. © 2003 Wiley-Liss, Inc. [source]

Circuits and systems in stress.


Abstract This paper follows the preclinical work on the effects of stress on neurobiological and neuroendocrine systems and provides a comprehensive working model for understanding the pathophysiology of posttraumatic stress disorder (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed. Specific brain areas that play an important role in a variety of types of memory are also preferentially affected by stress, including hippocampus, amygdala, medial prefrontal cortex, and cingulate. This review indicates the involvement of these brain systems in the stress response, and in learning and memory. Affected systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary-adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis), and neuro-immunological alterations) as well as changes found with structural and functional neuroimaging methods. Converging evidence has emphasized the role of early-life trauma in the development of PTSD and other trauma-related disorders. Current and new targets for systems that play a role in the neural circuitry of PTSD are discussed. This material provides a basis for understanding the psychopathology of stress-related disorders, in particular PTSD. Depression and Anxiety 16:14,38, 2002. © 2002 Wiley-Liss, Inc. [source]

Characterization of natural vasostatin-containing peptides in rat heart

FEBS JOURNAL, Issue 14 2006
Elise Glattard
Chromogranin A (CGA) is a protein that is stored and released together with neurotransmitters and hormones in the nervous, endocrine and diffuse neuroendocrine systems. As human vasostatins I and II [CGA(1,76) and CGA(1,113), respectively] have been reported to affect vessel motility and exert concentration-dependent cardiosuppressive effects on isolated whole heart preparations of eel, frog and rat (i.e. negative inotropism and antiadrenergic activity), we investigated the presence of vasostatin-containing peptides in rat heart. Rat heart extracts were purified by RP-HPLC, and the resulting fractions analyzed for the presence of CGA N-terminal fragments using dot-blot analysis. CGA-immunoreactive fractions were submitted to western blot and MS analysis using the TOF/TOF technique. Four endogenous N-terminal CGA-derived peptides [CGA(4,113), CGA(1,124), CGA(1,135) and CGA(1,199)] containing the vasostatin sequence were characterized. The following post-translational modifications of these fragments were identified: phosphorylation at Ser96, O-glycosylation (trisaccharide, NAcGal-Gal-NeuAc) at Thr126, and oxidation at three methionine residues. This first identification of CGA-derived peptides containing the vasostatin motif in rat heart supports their role in cardiac physiology by an autocrine/paracrine mechanism. [source]

Neuropeptide Y and alpha-melanocyte-stimulating hormone: interaction in obesity and possible role in the development of hypertension

M. Baltatzi
Summary Aim:, Obesity and hypertension frequently coexist and both represent important risk factors for cardiovascular disease. The mechanisms implicated in the regulation of food intake have not been completely elucidated. Recent data suggests that peripheral and central neuropeptides play an important role in the maintenance of energy balance. More specifically, leptin, neuropeptide Y (NPY) and alpha-melanocyte-stimulating hormone (a-MSH) appear to be implicated in the pathogenesis of obesity and also contribute to the development of hypertension in obesity. Methods:, Analysis of the pertinent bibliography published in PubMed database. Results:, Leptin is produced in the adipose tissue directly correlated with fat tissue mass. Leptin acts on two distinct neural populations in the hypothalamus: the first expresses the orexigenic peptides NPY and agouti-related protein (AgRP), the second pro-opiomelanocortin (POMC). The activation of POMC neurons increases the production of the anorexigenic hormone a-MSH and inhibits the release of NPY and AgRP. In addition, the hypothalamus integrates the neuroendocrine systems with the autonomic nervous system and controls the activity of the latter. Stimulation of hypothalamic nuclei elicits sympathetic responses including blood pressure elevation. Both NPY and a-MSH appears to be implicated in the hypothalamic regulation of sympathetic nervous system (SNS) activity. Conclusion:, Alterations in leptin, NPY and a-MSH are frequently observed in obesity and might stimulate SNS activity, contributing to the development of hypertension in obese patients. These neuropeptides might provide a pathophysiologic link between excess weight and hypertension. However, more research is needed before the pharmacologic manipulation of these complex neuroendocrine systems can be applied in the treatment of obesity and hypertension. [source]

Functional expression of corticotropin-releasing hormone (CRH) receptor 1 in cultured rat microglia

Wei Wang
Abstract Corticotropin-releasing hormone (CRH), known as a key regulator of the hypothalamic,pituitary,adrenal axis response to stress, elicits its biological effects by binding to two membrane receptors (CRH-R1 and CRH-R2). The present studies examined the presence of functional expression of CRH receptors in cultured microglia of rat. CRH-R1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR), western blotting and receptor chemical cross-linking assay in cultured microglia. CRH-R2 mRNA was undectable by RT-PCR. The radioligand binding analysis using [125I]Tyr-rat/human CRH revealed a high affinity binding site (Kd of 1.2 nm and Bmax of 84 fmol/mg of protein). Competition studies using CRH and related peptides indicated kinetic and pharmacological characteristics consistent with the CRH-R1 receptor subtype. Receptor chemical cross-linking assay demonstrated a single band of CRH receptor with a molecular weight of ,77 kDa, which was inhibited in the presence of excess unlabeled rat/human CRH in a dose-dependent manner and inhibited by a CRH receptor,antagonist astressin. Functional coupled cAMP production in cultured microglia was stimulated by exogenous addition of CRH and related peptides in a dose-dependent manner and blocked by astressin. Our findings suggest the functional expression of CRH-R1 receptor in rat microglia, indicating an important mechanism of interaction between immune and neuroendocrine systems in brain physiological and,pathological conditions. [source]

Rhythm-Dependent Light Induction of the c-fos Gene in the Turkey Hypothalamus

A. Thayananuphat
Day length (photoperiod) is a powerful synchroniser of seasonal changes in the reproductive neuroendocrine activity in temperate-zone birds. When exposed to light during the photoinducible phase, reproductive neuroendocrine responses occur. However, the neuroendocrine systems involved in avian reproduction are poorly understood. We investigated the effect of light exposure at different circadian times upon the hypothalamus and components of the circadian system, using c-fos mRNA expression, measured by in situ hybridisation, as an indicator of light-induced neuronal activity. Levels of c-fos mRNA in these areas were compared after turkey hens (on a daily 6-h light period) had been exposed to a 30-min period of light occurring at 8, 14, or 20 h after the onset of first light of the day (subjective dawn). Non-photostimulated control birds were harvested at the same times. In birds, photostimulated within the photoinducibile phase (14 h), in contrast to before or after, c-fos mRNA was significantly increased in the nucleus commissurae pallii (nCPa), nucleus premamillaris (PMM), eminentia mediana (ME), and organum vasculosum lamina terminalis (OVLT). Photostimulation increased c-fos mRNA expression in the pineal gland, nucleus suprachiasmaticus, pars visualis (vSCN) and nucleus inferioris hypothalami compared to that of their corresponding nonphotostimulated controls. However, the magnitudes of the responses in these areas were similar irrespective of where in the dark period the pulses occurred. No c-fos mRNA was induced in the nucleus infundibulari, in response to the 30-min light period at any of the circadian times tested. The lack of c-fos up-regulation in the pineal gland and vSCN following photostimulation during the photoinducible phase lends credence to the hypothesis that these areas are not involved in the photic initiation of avian reproduction. On the other hand, c-fos mRNA increases in the nCPa, ME, and OVLT support other studies showing that these areas are involved in the onset of reproductive behaviour initiated by long day lengths. The present study provides novel data showing that the PMM in the caudal hypothalamus is involved in the neuronally mediated, light-induced initiation of reproductive activity in the turkey hen. [source]

Anatomical Markers of Activity in Neuroendocrine Systems: Are we all ,Fos-ed out'?

G. E. Hoffman
Abstract It has now been nearly 15 years since the immediate early gene, c -fos, and its protein product, Fos, were introduced as tools for determining activity changes within neurones of the nervous system. In the ensuing years, this approach was applied to neuroendocrine study with success. With it have come advances in our understanding of which neuroendocrine neurones respond to various stimuli and how other central nervous system components interact with neuroendocrine neurones. Use of combined tract-tracing approaches, as well as double-labelling for Fos and transmitter markers, have added to characterization of neuroendocrine circuits. The delineation of the signal transduction cascades that induce Fos expression has led to establishment of the relationship between neurone firing and Fos expression. Importantly, we can now appreciate that Fos expression is often, but not always, associated with increased neuronal firing and vice versa. There are remaining gaps in our understanding of Fos in the nervous system. To date, knowledge of what Fos does after it is expressed is still limited. The transience of Fos expression after stimulation (especially if the stimulus is persistent) complicates design of experiments to assess the function of Fos and makes Fos of little value as a marker for long-term changes in neurone activity. In this regard, alternative approaches must be sought. Useful alternative approaches employed to date to monitor neuronal changes in activity include examination of (i) signal transduction intermediates (e.g. phosphorylated CREB); (ii) transcriptional/translational intermediates (e.g. heteronuclear RNA, messenger RNA (mRNA), prohormones); and (iii) receptor translocation. Another capitalizes on the fact that many neuroendocrine systems show striking stimulus-transcription coupling in the regulation of their transmitter or its synthetic enzymes. Together, as we move into the 21st Century, the use of multiple approaches to study activity within neuroendocrine systems will further our understanding of these important systems. [source]

Growth hormone and insulin-like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

N Önenli-Mungan
Objectives: Despite improved supportive care, the mortality of sepsis and septic shock is still high. Multiple changes in the neuroendocrine systems, at least in part, are responsible for the high morbidity and mortality. A reduced circulating level of insulin-like growth factor and an elevated level of growth hormone are the reported characteristic findings early in the course of sepsis and septic shock in adults. The aim of this study was to evaluate the changes of growth hormone/insulin-like growth factor 1 axis in sepsis and septic shock and investigate the relationship between these hormones and survival. Methods: Fifty-one children with sepsis (S), 21 children with septic shock (SS) and 30 healthy, age- and sex-matched children (C) were enrolled in this study. Growth hormone, insulin-like growth factor 1 and cortisol levels of the sepsis and septic shock groups were obtained before administration of any inotropic agent. Results: Growth hormone levels were 32.3 ± 1.5 µIU/mL (range 4,56), 15.9 ± 0.6 µIU/mL (range 11,28) and 55.7 ± 2.7 µIU/mL (range 20,70) in S, C and SS groups, respectively. The difference between the growth hormone levels of the S and C groups, S and SS groups, and C and SS groups were significant (P < 0.001). Non-survivors (54.7 ± 1.6 µIU/mL) had significantly higher growth hormone levels than survivors (29.4 ± 1.5 µIU/mL) (P < 0.001). Insulin-like growth factor 1 levels were 38.1 ± 2.1 ng/mL (range 19,100), 122.9 ± 9.6 ng/mL (range 48,250) and 22.2 ± 1.9 ng/mL (range 10,46) in the S, C and SS groups, respectively, and the difference between the insulin-like growth factor 1 levels of the S and C, S and SS, and C and SS groups were significant (P < 0.001). Non-survivors (8.8 ± 1.1 µg/dL) had significantly lower cortisol levels than survivors (40.9 ± 2.1 µg/dL) (P < 0.001). We detected a significant difference between the levels of cortisol in non-survivors (19.7 ± 1.8 µg/dL) and survivors (33.9 ± 0.9 µg/dL) (P < 0.01). Conclusions: There were elevated levels of growth hormone with decreased levels of insulin-like growth factor 1 in children during sepsis and septic shock compared to healthy subjects. In addition, there were even higher levels of growth hormone and lower levels of insulin-like growth factor 1 in non-survivors than in survivors. We think that both growth hormone and insulin-like growth factor 1 may have potential prognostic value to serve as a marker in bacterial sepsis and septic shock in children. As there is insufficient data in the paediatric age group, more studies including large numbers of patients and additionally evaluating cytokines and insulin-like growth factor binding proteins are needed. [source]

HPLC determination of acidic d -amino acids and their N -methyl derivatives in biological tissues

Mara Tsesarskaia
Abstract d -Aspartate (d -Asp) and N -methyl- d -aspartate (NMDA) occur in the neuroendocrine systems of vertebrates and invertebrates, where they play a role in hormone release and synthesis, neurotransmission, and memory and learning. N -methyl- d -glutamate (NMDG) has also been detected in marine bivalves. Several methods have been used to detect these amino acids, but they require pretreatment of tissue samples with o -phthaldialdehyde (OPA) to remove primary amino acids that interfere with the detection of NMDA and NMDG. We report here a one-step derivatization procedure with the chiral reagent N-, -(5-fluoro-2,4-dinitrophenyl)-(d or l)-valine amide, FDNP-Val-NH2, a close analog of Marfey's reagent but with better resolution and higher molar absorptivity. The diastereomers formed were separated by HPLC on an ODS-Hypersil column eluted with TFA/water,TFA/MeCN. UV absorption at 340 nm permitted detection levels as low as 5,10 pmol. d -Asp, NMDA and NMDG peaks were not obscured by other primary or secondary amino acids; hence pretreatment of tissues with OPA was not required. This method is highly reliable and fast (less than 40 min HPLC run). Using this method, we detected d -Asp, NMDA and NMDG in several biological tissues (octopus brain, optical lobe and bucchal mass; foot and mantle of the mollusk Scapharca broughtonii), confirming the results of other researchers. Copyright © 2009 John Wiley & Sons, Ltd. [source]