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)

It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which central serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT(2C)R) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus.
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PMID:Central serotonin and melanocortin pathways regulating energy homeostasis. 1285 13

Serotonin (5-hydroxytryptamine, 5-HT)-containing neurons in the midbrain directly innervate corticotropin-releasing hormone (CRH)-containing cells located in paraventricular nucleus of the hypothalamus. Serotonergic inputs into the paraventricular nucleus mediate the release of CRH, leading to the release of adrenocorticotropin, which triggers glucocorticoid secretion from the adrenal cortex. 5-HT1A and 5-HT2A receptors are the main receptors mediating the serotonergic stimulation of the hypothalamic-pituitary-adrenal axis. In turn, both CRH and glucocorticoids have multiple and complex effects on the serotonergic neurons. Therefore, these two systems are interwoven and communicate closely. The intimate relationship between serotonin and the hypothalamic-pituitary-adrenal axis is of great importance in normal physiology such as circadian rhythm and stress, as well as pathophysiological disorders such as depression, anxiety, eating disorders, and chronic fatigue.
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PMID:Serotonin and the neuroendocrine regulation of the hypothalamic--pituitary-adrenal axis in health and disease. 1285 56

Isolated juvenile rainbow trout were fed a feed supplemented with L-tryptophan (TRP) for 3, 7 or 28 days, after which they were either sampled directly (undisturbed) or subjected to a standardised stressor prior to sampling. Controls (stressed and undisturbed) received the same feed but without any supplementary TRP. Stress resulted in a significant elevation of plasma [cortisol] in fish fed control feed and in fish fed TRP-supplemented feed for 3 and 28 days. However, fish fed TRP-supplemented feed for 7 days did not show any significant elevation of plasma [cortisol] in response to stress. Plasma levels of adrenocorticotropin followed the same general pattern as cortisol. Plasma and brain [TRP] were elevated in fish fed TRP-supplemented feed. The amino acid TRP is the precursor of the monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) and the brain 5-HT system is known to be involved in the control of the hypothalamic-pituitary-interrenal (HPI) axis. Fish fed TRP-supplemented feed showed elevated levels of 5-hydroxyindoleacetic acid (5-HIAA, a major 5-HT metabolite) in the hypothalamus and optic tectum. However, TRP treatment did not appear to result in any effects on brain dopaminergic activity and the effects on brain norepinephric activity do not support a role of norepinephrine in mediating the effects of TRP on HPI axis reactivity in rainbow trout.
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PMID:Time-course of the effect of dietary L-tryptophan on plasma cortisol levels in rainbow trout Oncorhynchus mykiss. 1296 50

Specimens of testis, excurrent duct including the male accessory glands and urethra, were studied in boars, bulls, horses and donkeys, in order to localize endocrine/paracrine cells. Silver impregnation methods were used to test the argentaffinity and/or argyrophilia of cells. Immunoreactivities to chromogranin A, 5-hydroxytryptamine, somatostatin, [met]- and [leu]- enkephalins, gastrin-releasing peptide, calcitonin gene-related peptide, neuropeptide Y, substance P, vasoactive intestinal peptide, beta-endorphin antisera were tested by a streptavidin-biotin method. In the testis, epididymis, ductus deferens and vesicular gland no endocrine cells were found in any of the animals studied. Chromogranin-A, serotonin, somatostatin and enkephalins were present in endocrine/paracrine cells in the surface or glandular epithelia, whereas all other antisera gave negative results. In the prostatic complex and the urethral epithelium, the most consistent number of endocrine cells was serotonin-immunoreactive. Few cells were also argentaffin and a very limited number of them showed argyrophily and chromogranin-A immunoreactivity. Somatostatin-and enkephalin-immunoreactive cells were rare in the bull and boar, absent in stallions. This comparative study carried out on different species of domestic ungulates has shown deeply different immunophenotypes, even comparing species that are in a very close zoological relationship with one another, such as the horse and the donkey.
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PMID:Endocrine-paracrine cells of the male urogenital apparatus: a comparative histochemical and immunohistochemical study in some domestic ungulates. 1523 14

The molecular mechanisms that control the range and stability of emotions are unknown, yet this knowledge is critical for understanding mood disorders, especially bipolar illness. Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated transgenic mice overexpressing GR specifically in forebrain. These mice display a significant increase in anxiety-like and depressant-like behaviors relative to wild type. Yet, they are also supersensitive to antidepressants and show enhanced sensitization to cocaine. Thus, mice overexpressing GR in forebrain have a consistently wider than normal range of reactivity in both positive and negative emotionality tests. This phenotype is associated, in specific brain regions, with increased expression of genes relevant to emotionality: corticotropin-releasing hormone, serotonin, norepinephrine and dopamine transporters, and 5-hydroxytryptamine(1A) receptor. Thus, GR overexpression in forebrain causes higher "emotional lability" secondary to a unique pattern of molecular regulation. This finding suggests that natural variations in GR gene expression can contribute to the fine-tuning of emotional stability or lability and may play a role in bipolar disorder.
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PMID:Glucocorticoid receptor overexpression in forebrain: a mouse model of increased emotional lability. 1528 May 45

The secretion of cortisol and other steroids from adrenal tumors can be regulated by hormones other than corticotropin following the aberrant expression of several G-protein-coupled receptors (GPCRs). To date, ectopic receptors for gastric inhibitory polypeptide, beta-adrenergic receptor agonists, vasopressin (V(2) and V(3) receptors), 5-hydroxytryptamine (5-HT(7) receptor) and, probably, angiotensin II (AT(1) receptor) have been identified. Either increased expression or altered activity of eutopic receptors for vasopressin (V(1)), luteinizing hormone/human chorionic gonadotropin, 5-HT (5-HT(4) receptor) and leptin might also be involved. One or more aberrant receptors can be present in unilateral tumors and bilateral macronodular adrenal hyperplasia, at either the early subclinical or overt stages of hormone secretion. The identification of aberrant adrenal GPCRs offers the potential for novel pharmacological therapies that either suppress the endogenous ligands or block the receptor with specific antagonists.
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PMID:Cushing's syndrome variants secondary to aberrant hormone receptors. 1538 Aug 9

Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors.
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PMID:Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences. 1557 37

The cerebellum, probably owing to its traditional concept limited to motor control, is less well studied in immunoregulation. To obtain more comprehension and knowledge on cerebellar functions, we investigated effect of cerebellar fastigial nucleus (FN), an output nucleus of the spinocerebellum, on lymphocyte functions, and explored central and peripheral pathways involved in the effect. Kainic acid (KA) was microinjected into bilateral FN of rats (0.4 microg KA in 0.4 microl saline for each side) to destroy neurons of the nuclei. On days 8, 16 and 32 following the FN lesions, methyl-thiazole-tetrazolium (MTT) assay and flow cytometry were used to measure proliferation of concanavalin A (Con A)-induced lymphocytes and cytotoxicity of natural killer (NK) cells against YAC-1 cells, respectively. Meanwhile, glutamate and monoamine neurotransmitters, including norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT), in the hypothalamus and the spleen were determined by means of high-performance liquid chromatography (HPLC) assay. Adrenocorticotropic hormone (ACTH) and cortisol in the plasma were also detected respectively by radioimmunoassay and chemiluminescent immunoassay after the FN lesions. We found that the Con A-induced lymphocyte proliferation and the NK cell cytotoxicity were both significantly enhanced on days 8, 16 and 32 following the effective lesions of the bilateral FN in comparison with those of matching control rats microinjected with saline in their FN. Contents of glutamate and NE, not DA and 5-HT, in the hypothalamus, and concentration of NE, not DA, in the spleen were all remarkably reduced on the 16th day following the FN lesions, when both the T lymphocyte proliferation and the NK cell cytotoxicity were dramatically increased. However, levels of ACTH and cortisol in the plasma had no notable differences between FN lesion rats and FN saline ones when the enhanced T and NK cell functions occurred. These findings reveal that the cerebellar FN participates in the modulation of lymphocyte functions and that the hypothalamus and sympathetic nerves innervating lymphoid organs are involved in this neuroimmunomodulation. Thus, a possible central and peripheral pathway for the spinocerebellum to regulate lymphocyte functions is suggested, i.e. cerebellum-hypothalamus-sympathetic nerves-lymphocytes, while the functional axis of hypothalamus-pituitary-adrenal gland may not contribute to mediation of the spinocerebellar immunomodulation.
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PMID:Effect of lesions of cerebellar fastigial nuclei on lymphocyte functions of rats. 1571 Apr 91

Neuroendocrine responses to administration of serotonin releasing agents or 5-hydroxytryptamine (5-HT) 1A receptor agonists have been used as an index of serotonin receptor function in patients with depression and other mood disorders. However, the receptor population that mediates these responses has not been clearly identified. We tested the hypothesis that 5-HT1A receptors in the paraventricular nucleus of the hypothalamus (PVN) mediate the release of adrenocorticotropin hormone (ACTH) and oxytocin after administration of a selective 5-HT1A agonist in conscious rats. Low-dose infusion (1 nmol/100 nl/side) of the selective 5-HT1A antagonist, WAY100635 (WAY; [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-(2-pyridinyl)cyclohexanecarboxamidetrihydrochloride), into the PVN blocked the rise in ACTH and oxytocin stimulated by low-dose (30 nmol/kg) i.v. administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 274 +/- 53 versus 70 +/- 20 pg/ml, P < 0.01 for ACTH and 10.7 +/- 3.4 versus 4.6 +/- 0.7 pg/ml, P < 0.05 for oxytocin after saline or WAY pretreatment, respectively). WAY did not influence the bradycardic effect of 8-OH-DPAT (-56 +/- 7 versus -54 +/- 6 beats per minute after saline or WAY). 8-OH-DPAT treatment also elicited locomotor activation followed by hind limb abduction and flat body posture. Surprisingly, WAY attenuated some aspects of locomotor activation and reduced the duration of hind limb abduction elicited by the agonist (5.1 +/- 0.9 versus 0.3 +/- 0.3 min for saline- or WAY-treated rats). These data indicate that 5-HT1A receptor stimulation in the PVN mediates the characteristic neuroendocrine response to serotonin agonist challenge. Moreover, they provide the first evidence that aspects of the behavioral serotonin syndrome are mediated by forebrain hypothalamic receptors.
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PMID:5-Hydroxytryptamine 1A receptors in the paraventricular nucleus of the hypothalamus mediate oxytocin and adrenocorticotropin hormone release and some behavioral components of the serotonin syndrome. 1574 27

Feeding and energy expenditures are modulated by the interplay of hormones and neurotransmitters in the central nervous system (CNS), where the hypothalamus plays a pivotal role in the transduction of peripheral afferents into satiety and feeding signals. Aminergic neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) are historically considered to play a key role, but a number of peptides are involved in finely tuning feeding regulation. This review summarizes the current understanding of the CNS mechanisms of orexigenic peptides, such as neuropeptide Y, orexins, and ghrelin, as well as anorectic peptides, such as leptin, neurotensin (NT), cocaine- and amphetamine regulated transcript (CART) peptide, thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), urocortin, amylin.
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PMID:The regulation of feeding: a cross talk between peripheral and central signalling. 1588 44


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