Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model employing perfusion of artificial cerebrospinal fluid from the lateral ventricle to the cisterna magna in the halothane anesthetized rat was used to study beta-endorphin release in the brain. Injection of 75 micrograms capsaicin into the lumbar intrathecal space released beta-endorphin immunoreactivity into perfusate. The release was blocked by intrathecal pretreatment with 1.25 mg lidocaine and the capsaicin receptor antagonist capsazepine (92 micrograms), showing that the release is caused by binding of capsaicin to a spinal receptor. The release was also blocked by intrathecal pretreatment with the NMDA antagonist MK-801 (3 micrograms) and the NK-1 receptor antagonist CP96,345 (200 micrograms), whereas the AMPA receptor antagonist NBQX (6 micrograms) yielded no significant inhibition. Surprisingly, morphine (30 micrograms) and sufentanil (1.5 micrograms) did not prevent release of beta-endorphin immunoreactivity, although blocking the cardiovascular responses to a noxious heat stimulus. High performance liquid chromatography characterization of perfusates collected after capsaicin injection showed that all beta-endorphin immunoreactivity coeluted with authentic beta-endorphin1-31. beta-Endorphin immunoreactivity in plasma was increased 10 min, but not 25 min, after capsaicin injection. Capsaicin injection abolished the motor and cardiovascular responses to tail immersion in 52.5 degrees C water. Addition of MK-801 (10(-4) mol/l) to the lateral ventricle-cisterna magna perfusate blocked the capsaicin-induced beta-endorphin release, showing that our previous demonstration of an NMDA receptor regulating arcuate nucleus beta-endorphin neuron activity has functional significance. We conclude that in this in vivo, anesthetized preparation including three hot water tail immersions, beta-endorphin can be released into a ventriculo-cisternal perfusate, by activation of the central axons of small primary afferent neurons by capsaicin. These data support the idea that central beta-endorphin may be released in response to prolonged, intense noxious stimulation.
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PMID:Release of beta-endorphin immunoreactivity into ventriculo-cisternal perfusate by lumbar intrathecal capsaicin in the rat. 892 84

The tubby mouse is characterized by an autosomal recessive mutation which results in the development of maturity-onset obesity and sensorineural hearing loss and retinal degeneration. Although the tubby mutation which leads to a splicing defect of the tub gene has been identified recently, the mechanism by which it causes the obesity syndrome has not been established. In this study, the potential dysfunction of several hypothalamic neuroendocrine pathways involved in the central regulation of energy metabolism was investigated in tubby mice. In comparison with the wild-type controls, a significant reduction (20%) of pro-opiomelanocortin (POMC) mRNA expression was observed in the arcuate nucleus (ARC) of the mature, obese but not in the juvenile, non-obese tubby mice. Similarly, an age and body mass-dependent induction (about 30-fold) of neuropeptide Y (NPY) mRNA was observed in the dorsomedial (DMH) and ventromedial (VMH) hypothalamic nuclei of the tubby mice. However, NPY mRNA in the ARC was decreased by approximately 30 to 40% in both juvenile and mature tubby mice. The hypothalamic expression patterns of corticotropin releasing hormone (CRH) and the long form leptin receptor (OB-Rb) were not significantly altered in the mutant mice. These results suggest that the altered hypothalamic POMC and/or NPY functions may be important contributing factors for the development of obesity in this animal model.
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PMID:Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. 972 27

The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus. To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor (Ob-Rb). Thus, mRNAs encoding NPY and pro-opiomelanocortin (POMC) were colocalized in the arcuate nucleus of fed and fasted rats by fluorescence in situ hybridization in combination with isotopic in situ hybridization for Ob-Rb mRNA. In fed animals, 47% of arcuate nucleus neurons containing NPY mRNA also contained Ob-Rb mRNA, compared with 79% of POMC neurons (P < 0.01). After a 2-day fast, the number of arcuate nucleus neurons with NPY mRNA increased 50% (P < 0.05); the number of these that coexpressed Ob-Rb increased twofold (P = 0.013). Furthermore, Ob-Rb mRNA hybridization in individual NPY neurons increased by 64% (P < 0.02). In contrast, the number of POMC neurons that coexpressed Ob-Rb was unchanged. A significant interpretation of these findings is that the NPY neurons that do not express detectable levels of Ob-Rb mRNA are not activated by fasting, whereas the NPY neurons that are activated by fasting are the ones that express Ob-Rb. These data demonstrate a significant physiological difference between NPY neurons that express Ob-Rb and those that do not. The results support the conclusion that the effect of food intake on NPY neurons is mediated by the direct action of leptin via Ob-Rb receptors expressed by these NPY cells. The results also indicate that expression of Ob-Rb is a defining phenotypic characteristic of the subset of arcuate nucleus NPY neurons that are activated by fasting and play a central role in the adaptive response to negative energy balance.
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PMID:Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. 1010

The thymus provides an optimal humoral microenvironment for the development of immunocompetent T cells. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The majority of RE cells have a round or irregular pale nucleus, which contains few, scattered, chromatin granules with a defined, spherical nucleolus, rich in basic histones. Their cytoplasm occasionally displays RNP granules, and is rich in non-histone proteins, fine phospholipid, lipid or cholesterin granules, and vacuoles filled with secreted substances. The cells of the subcapsular, endocrine RE cell layer (giant or nurse cells), characterized by PAS positive granules, express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to medullar RE cells, these subcapsular nurse cells also produce thymosins beta 3 beta 4. Thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA-DR) molecule restriction. These cells also contain transforming growth factor-beta (TGF-beta) type II receptors and participate in the positive selection of T cells. Transmission electron-microscopic (TEM) observations have defined four functional subtypes of medullar RE cells: undifferentiated, squamous, villous, and cystic. All subtypes are connected by desmosomes. Immunocytochemical observations have shown that the secreted thymic hormones, thymosin alpha 1 and thymopoietin (and its short form, thymopentin or TP5), are produced by the same RE cells. Thymic RE cells also produce numerous cytokines including IL1, IL6, G-CSF, M-CSF, and GM-CSF that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion, such as growth hormone, prolactin, adrenocorticotropic hormone, thyroid stimulating hormone, triiodothyronine, somatostatin, oxytocin, follicle stimulating hormone, luteinizing hormone, arginine vasopressin, growth hormone releasing hormone, corticotropin releasing hormone, nerve growth factor, vasoactive intestinal peptide, (pro) enkephalin, and beta-endorphin, production of a number of interleukins and growth factors, as well as the expression of receptors for all, by the same RE cell is an unique molecular biological phenomenon. These data illustrate the immensely important and diverse immuno-neuroendocrine functions of the thymic RE cellular network. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cell network represents an extremely important cellular and humoral microenvironment in homeopathic regulatory mechanisms of the multicellular organism. Intrathymic T lymphocyte selection is a complex, multistep process, influenced by several functionally specialized RE cell subtypes and under constant immuno-neuroendocrine regulation, reflecting the dynamic changes of the organism.
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PMID:Molecular biological ontogenesis of the thymic reticulo-epithelial cell network during the organization of the cellular microenvironment. 1045 6

Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin (POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes, male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism. STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/- 0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40% more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/- 2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by 80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone (CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. The effect of uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. These responses, in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on fuel metabolism in peripheral tissues.
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PMID:Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. 1086 41

The thyrnus provides an optimal cellular and humoral microenvironment for the development of immunocompetent T lymphocytes. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide, called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The thymic RE cells are functionally specialized based on their location within the thymic microenvironment. Thus, although subcapsular, cortical, and medullary RE cells are derived from a common, endodermal in origin epithelial precursor cell, their unique location within the gland causes their specialization in terms of their immunophenotypical and in situ physiological properties. The subcapsular, endocrine, RE cell layer (giant or nurse cells) is comprised of cells filled with PAS positive granules, which also express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to the medullary RE cells, these subcapsular nurse cells also produce thymosins beta 3 and beta 4. The thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA- DR) molecule restriction. These cells also contain transforming growth factor (TGF)-beta type II receptors and are involved in the positive selection of T cells. Transmission electronmicroscopic (TEM) observations have defined four, functional subtypes of medullary RE cells: undifferentiated squamous, villous and cystic. All subtypes were connected with desmosomes. The secreted thy nic hormones, thymulin, thymosin-alpha 1 and thymopoietin (its short form, thymopentin or TP5) were detected immunocytochemically to be produced by RE cells. Thymic RE cells also produce numerous cytokines including IL-1, IL-6, G-CSF, M-CSF, and GM-CSF molecules that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion [growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), triiodothyronine (T3), somatostatin, oxytocin (OT), follicle stimulating hormone (FSH), luteinizing hormone (LH), arginine vasopressin (AVP), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRH), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), pro-enkephalin (pro-enk), and beta-endorphin (beta-end)], as well as production of a number of interleukins and growth factors and expression of receptors for all, by RE cells is an unique molecular biological phenomenon. The thymic RE cell network is most probably comprised of cells organized into sub-networks--functional units composed of RE cells with differing hormone production/hormone receptor expression profiles, involved in the various stages of T lymphocyte maturation. Furthermore, it is quite possible that even on the level of individual RE cells, the numerous projections associated with a single cell, which engulf developing lymphocytes, nurturing and guiding them in their maturation, may differ in their hormone production and/or hormone receptor expression profile, thus allowing a single cell to be involved in distinct, separate steps of the T cell maturation process. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cells represent an extremely important cellular and humoral network within the thymic microenvironment and are involved in the homeopathic regulation mechanisms of the multicellular organism, in addition to the presentation of various antigens to developing lymphocytes, and providing growth regulatory signals which may range from stimulatory to apoptotic signaling within the thymus. (ABSTRACT TRUNCA
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PMID:The role of the reticulo-epithelial (RE) cell network in the immuno-neuroendocrine regulation of intrathymic lymphopoiesis. 1092 21

The hypothalamic-pituitary-thyroid axis is down-regulated during starvation, and falling levels of leptin are a critical signal for this adaptation, acting to suppress preprothyrotropin-releasing hormone (prepro-TRH) mRNA expression in the paraventricular nucleus of the hypothalamus. This study addresses the mechanism for this regulation, using primary cultures of fetal rat hypothalamic neurons as a model system. Leptin dose-dependently stimulated a 10-fold increase in pro-TRH biosynthesis, with a maximum response at 10 nm. TRH release was quantified using immunoprecipitation, followed by isoelectric focusing gel electrophoresis and specific TRH radioimmunoassay. Leptin stimulated TRH release by 7-fold. Immunocytochemistry revealed that a substantial population of cells expressed TRH or leptin receptors and that 8-13% of those expressing leptin receptors coexpressed TRH. Leptin produced a 5-fold induction of luciferase activity in CV-1 cells transfected with a TRH promoter and the long form of the leptin receptor cDNA. Although the above data are consistent with a direct ability of leptin to promote TRH biosynthesis through actions on TRH neurons, addition of alpha-melanocyte-stimulating hormone produced a 3.5-fold increase in TRH biosynthesis and release, whereas neuropeptide Y treatment suppressed pro-TRH biosynthesis approximately 3-fold. Furthermore, the melanocortin-4 receptor antagonist SHU9119 partially inhibited leptin-stimulated TRH release from the neuronal culture. Consequently, our data suggest that leptin regulates the TRH neurons through both direct and indirect pathways.
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PMID:Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways. 1096 95

The effects of topiramate on food intake and body composition were investigated in rats fed a high-fat diet and compared with rats that were pair fed or treated with D-fenfluramine. Topiramate (40 mg. kg. d for 80 d) reduced body-weight gain in a manner similar to that of pair-fed rats and D-fenfluramine-treated rats. The reduction in body fat accounted for all the weight reduction after topiramate treatment but not after pair feeding or D-fenfluramine treatment. Topiramate reduced food intake acutely and increased metabolic rate. There were also significant reductions in leptin, insulin, and corticosterone. In the hypothalamus, topiramate increased mRNA for neuropeptide Y, reduced mRNA for neuropeptide-Y Y1 and Y5 receptors, corticotropin-releasing hormone (CRH), and type II glucocorticoid receptors but had no effect on mRNA levels for the short or long form of the leptin receptor. In peripheral tissues, topiramate reduced leptin mRNA in adipose tissue, had no effect on uncoupling protein 1 mRNA in brown adipose tissue but had tissue-selective effects on uncoupling proteins 2 and 3 mRNA levels in white and brown adipose tissues and muscle. In conclusion, topiramate is an effective inhibitor of weight gain in rats on a high-fat diet, but the mechanism through which the change in energy balance is achieved is unclear.
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PMID:Effect of topiramate on body weight and body composition of osborne-mendel rats fed a high-fat diet: alterations in hormones, neuropeptide, and uncoupling-protein mRNAs. 1105 3

We provide the first evidence that prolactin is a neuromodulator of behavioral and neuroendocrine stress coping in the rat. In virgin female and male rats, intracerebral infusion of ovine prolactin (oPRL) into the lateral cerebral ventricle (intracerebroventricular) exerted an anxiolytic effect on the elevated plus-maze in a dose-dependent manner (0.1 and 1.0 microg/5 microl; p < 0.01). In contrast, downregulation of the expression of the long form of brain prolactin receptors by chronic intracerebroventricular infusion of an antisense oligodeoxynucleotide (ODN) (osmotic minipump, 0.5 microg. 0.5 microl(-1). hr(-1); 5 d) increased anxiety-related behavior on the plus-maze compared with mixed bases-treated and vehicle-treated rats (p < 0.01), again demonstrating an anxiolytic effect of PRL acting at brain level. Furthermore, in jugular vein-catheterized female rats, the stress-induced increase of corticotropin secretion was decreased after chronic intracerebroventricular infusion of oPRL (osmotic minipump, 1.0 microg. 0.5 microl(-1). hr(-1); p < 0.05) and, in contrast, was further elevated by antisense targeting of the brain prolactin receptors (p < 0.01). This provides evidence for a receptor-mediated attenuation of the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis by prolactin. The antisense ODN sequence was selected on the basis of secondary structure molecular modeling of the target mRNA to improve antisense ODN-mRNA hybridization. Receptor autoradiography confirmed the expected improvement in the efficacy of downregulation of prolactin receptor expression [empirically designed antisense, 30%; p > 0.05, not significant; adjustment of target position after mRNA modeling, 72%; p < 0.05). Taken together, prolactin acting at brain level has to be considered as a novel regulator of both emotionality and HPA axis reactivity.
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PMID:Anxiolytic and anti-stress effects of brain prolactin: improved efficacy of antisense targeting of the prolactin receptor by molecular modeling. 1131 5

Prolactin (PRL) has recently been shown to exert an anxiolytic effect in male and virgin female rats, as well as an inhibitory tone on hypothalamic-pituitary-adrenal (HPA) axis activity. Reduced emotional and neuroendocrine stress responses have been described in lactation, a time of high blood PRL levels. Here we tested brain PRL-receptor (PRL-R)-mediated effects on anxiety, maternal behaviour, HPA axis and oxytocin stress responses in lactating rats. Chronic intracerebroventricular (i.c.v.) infusion of antisense oligonucleotides against the long form of the PRL-R (AS; osmotic minipump, 0.5 microg/0.5 microL/h) in order to downregulate brain PRL-R expression increased the anxiety-related behaviour on the elevated plus maze (P < 0.01) compared with mixed bases- and vehicle-treated rats. Also, PRL-R AS treatment impaired maternal behaviour (P < 0.05), whereas physiological parameters of lactation (weight gain of the litter, number of milk ejection reflexes during a 20-min suckling period) were not affected. PRL-R AS treatment further evoked an increase (P < 0.05) in the stress-induced adrenocorticotropin release, demonstrating an inhibitory role of PRL on HPA axis responses in lactation. Inhibition of stress responses of the oxytocin system by brain PRL was evidenced by higher stress-induced (P < 0.05) plasma oxytocin concentration in PRL-R AS-treated lactating rats and, in contrast, decreased stress-induced oxytocin release (P < 0.01) in chronic i.c.v. ovine PRL-treated (1 microg/0.5 microL/h) virgin rats. Finally, an increased expression of the hypothalamic PRL gene was seen by RT-PCR in pregnancy and lactation, suggesting an activated state of the brain PRL system during the peripartum period. In summary, activation of the brain PRL system in the peripartum period significantly contributes to emotional and neuroendocrine adaptations, including downregulation of the responsiveness of the HPA axis and oxytocin systems to stressors seen at this time.
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PMID:Increased hypothalamic expression of prolactin in lactation: involvement in behavioural and neuroendocrine stress responses. 1199 32


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