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)

Cytokine-mediated anorexia is a component of "sickness behavior" and presents a significant obstacle in the treatment of chronic illnesses. We hypothesized an involvement of the hypothalamic arcuate nucleus (ARH) in mediating the anorexic effects of a systemic interleukin-1 (IL-1) challenge based on its content of peptidergic neurons involved in feeding, its expression of IL-1 receptors and its sensitivity to systemic IL-1. IL-1 (6 microg/kg, i.v.) was found to induce Fos expression in both pro-opiomelanocortin- and neuropeptide Y-expressing neurons in and around the ARH. Contrary to expectations, rats that had sustained lesions of the arcuate nucleus, produced by neonatal monosodium glutamate treatment, displayed a more pronounced suppression (by 25%) of food intake than nonlesioned controls when treated with IL-1 after a 20 hr fast. To confirm and further characterize this unexpected result, a second ablation method was used in a similar paradigm. Animals bearing knife cuts designed to sever major ARH projections displayed an even more accentuated loss of appetite (by 60%, relative to controls) in response to systemic IL-1. This effect exhibited at least some degree of specificity, because the knife cuts did not alter either IL-1 effects on another centrally mediated acute phase response (fever) or the anorexia produced by an alternate agent, fenfluramine. These results fail to support the hypothesized ARH mediation of IL-1-induced anorexia and may suggest rather that the net output of this cell group may serve normally to restrain cytokine-induced reductions in food intake.
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PMID:Involvement of the arcuate nucleus of the hypothalamus in interleukin-1-induced anorexia. 1207 4

The intermediate portion of the lateral septum (LSi) contains high levels of urocortin (UCN) peptide and type 2 corticotropin-releasing hormone (CRH) receptor (CRHR2) and has anatomic and functional connections with the lateral hypothalamus (LH). We tested the effect of UCN in the LSi on feeding. Injection of 10 or 30 pmol UCN into LSi significantly decreased feeding in food-deprived rats for 24 h without producing conditioned taste aversion (CTA). Pretreatment with a CRH receptor antagonist, alpha-helical CRH (alpha-hCRH), blocked the inhibitory effect of UCN on deprivation-induced feeding at 1 and 2 h postinjection. Furthermore, UCN in the LSi significantly decreased feeding induced by LH-injected orexin A at 2 and 4 h postinjection, and addition of alpha-hCRH blocked the inhibitory effect of UCN on orexin A-induced feeding. In conclusion, UCN significantly inhibits feeding induced by deprivation and LH-injected orexin A without producing a CTA, an effect that is mediated by CRHR2. These data define the LSi as an important site for UCN-induced anorexia and indicate that LSi UCN may influence orexin A feeding signals in the LH.
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PMID:Urocortin in the lateral septal area modulates feeding induced by orexin A in the lateral hypothalamus. 1212 48

Melanocortins are derived from posttranslational processing of the precursor protein pro-opiomelanocortin (POMC). The central melanocortinergic system consists of endogenous agonist alpha-melanocyte-stimulating hormone, the naturally occurring antagonist Agouti-related protein (AGRP), and two melanocortin receptors (MC3R, MC4R). Activation of central melanocortin receptors inhibits feeding and leads to weight loss, whereas blockade of the central melanocortin signaling pathway increases food consumption and promotes weight gain. This review will focus on the role of central melanocortin signaling in eating behavior and will evaluate studies of the neural pathways of POMC and AGRP systems, the effects of the central melanocortinergic system on food intake and body weight, and the regulation of hypothalamic POMC and AGRP neurons in response to altered feeding state and energy balance. In addition, this review will explore what is known about the interplay between the central melanocortinergic system and peripheral signals of energy homeostasis, i.e., leptin and glucocorticoids. Furthermore, evidence will be presented that genetic defects within the melanocortin signaling system are involved in determining susceptibility to obesity and anorexia in humans, and the therapeutic potential of melanocortin agonists and antagonists in the treatment of these disorders will be discussed.
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PMID:Role of central melanocortin signaling in eating disorders. 1239 56

A 78-year-old male was admitted to our hospital complaining of nausea, general fatigue and anorexia in November, 1999. Clinical findings on admission were weight loss and dehydration but surface lymph nodes were not palpable. Masses in the bilateral adrenal glands were detected by ultrasonography, computed tomography and magnetic resonance imaging. Laboratory examinations revealed hyponatremia and hyperkalemia. Subsequent endocrine function tests showed normal serum cortisol and increased adrenocorticotropic hormone (ACTH) levels. Rapid ACTH test and cortico-hormone releasing hormone (CRH) test revealed insufficient secretion of cortisol. The histological diagnosis of the adrenal gland by laparotomy was diffuse large B-cell lymphoma. We diagnosed primary adrenal lymphoma with adrenal insufficiency. The patient underwent hormone supplementary therapy and chemotherapy, but he died two months later. We report on this rare primary adrenal lymphoma case and summarize the reports of this disease in the Japanese literature.
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PMID:[Primary adrenal lymphoma: a case report and literature review in Japan]. 1241 91

The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related substances cause a wide variety of pathological alterations, with the most severe being progressive anorexia and body weight loss. These features suggest a possible involvement of the nervous system and endocrine organs, including the pituitary gland. TCDD-related toxicity is considered mainly to be mediated by the aryl hydrocarbon receptor (AHR) protein, which binds TCDD, and heterodimerizes with its partner protein, the aryl hydrocarbon receptor nuclear translocator (ARNT), and binds to xenobiotica responsive elements (XREs) in the promoter regions of biotransformation genes as well as genes involved in growth, differentiation and cellular homeostasis. In the present study, we have investigated the expression of AHR responsive genes in the pituitary of untreated and TCDD treated 129/SV/C57BL/6 mice in vivo and in pituitary cells in vitro. After TCDD or beta-naphthoflavone (beta NF) treatment, the relative levels of cytochrome P4501A1 (CYP1A1) mRNA and protein were dramatically increased in pituitary cells. The AHR repressor (AHRR) mRNA level was induced 7-13-fold by TCDD and beta NF. Furthermore, the expression of the adrenocorticotrophic hormone (ACTH) precursor, the proopiomelanocortin (POMC) gene, was investigated. A three-fold increase in POMC mRNA was observed in the pituitary of TCDD treated mice. POMC mRNA level was also increased in the pituitary cell line AtT-20 after TCDD treatment. The proteins encoded by POMC translational products, ACTH and beta-endorphin, were found with immunocytochemistry staining to be increased in AtT-20 cells after TCDD exposure. The presence of several XRE sequences in the promoter region and in the first intron of the human POMC gene suggest that the up-regulation of POMC expression in the pituitary may play a role in the endocrine alterations induced by TCDD. All together, the results point to the pituitary gland being a direct target for TCDD.
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PMID:Constitutive and TCDD-induced expression of Ah receptor-responsive genes in the pituitary. 1252 Jul 68

Neuropeptide Y (NPY) is a strong orexigenic neurotransmitter also known to modulate several neuroendocrine axes. alpha-Melanocyte-stimulating hormone (MSH) is an essential anorectic neuropeptide, acting on hypothalamic MC3/4 receptor subtypes. When given as an intracerebroventricular bolus injection, Melanotan-II (MT-II), a non selective MC receptor agonist, inhibits feeding, suppresses the NPY orexigenic action, and reduces basal insulinaemia. We evaluated the effects of a 7-day central infusion of MT-II (15 nmol/day) given either alone or in association with NPY (5 nmol/day) in male Sprague-Dawley rats. MT-II produced almost full anorexia for 1-2 days but then feeding gradually returned to normal despite continued MT-II infusion. When coinfused with NPY, MT-II also produced the same initial anorectic episode but then maintained feeding to upper normal levels, thus cancelling the hyperphagia driven by NPY. Whereas NPY infusion produced a doubling of fat pad weight, MT-II reduced adiposity by a factor of two compared to pair-fed rats, and vastly curtailed the NPY-driven increase in fat pad weight. MT-II infusion also significantly curtailed the NPY-induced rise in insulin and leptin secretions. NPY infusion significantly inhibited hypothalamic pro-opiomelanocortin mRNA expression, most likely cancelling the alpha-MSH anorectic activity. As expected from previous studies, chronic NPY infusion strongly inhibited both the gonadotropic and somatotropic axes, and coinfusion of MT-II did not reverse these NPY-driven effects, in sharp contrast with that seen for the metabolic data. MT-II infusion alone had little effect on these axes. In conclusion, chronic MT-II infusion generated a severe but transient reduction in feeding, suggesting an escape phenomenon, and clearly reduced fat pad size. When coinfused with NPY, MT-II was able to cancel most of the NPY effects on feeding, but not those on the neuroendocrine axes. It appears therefore that, as expected, NPY and alpha-MSH closely interact in the control of feeding, whereas the neural pathways by which NPY affects growth and reproduction are distinct and not sensitive to MC peptide modulation.
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PMID:The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat. 1253 59

Addison's disease due to adrenal lymphoma usually manifests as bilateral adrenal enlargement. We report a patient with Addsion's disease in whom the initial overt primary adrenal insufficiency was accompanied by an only slightly enlarged right adrenal gland. The 80-year-old man presented with nausea, anorexia, weight loss, and hyperpigmentation of the skin and buccal mucosa. Addison's disease was diagnosed based on this clinical presentation and laboratory findings of low cortisol and high adrenocorticotropin levels. Computerized tomography (CT) of the adrenal glands revealed a small right adrenal tumor. His family refused to allow percutaneous or surgical biopsy to determine the nature of the tumor. His general condition improved after steroid supplementation. However, about 1 year later, dizziness, fever, night sweats, and edema of the lower legs developed, and adrenal CT scanning revealed that the left adrenal gland had enlarged and now exceeded the size of the right one. Left adrenalectomy was performed and pathology showed a diffuse large B-cell lymphoma. Staging work-up using whole-body CT scanning suggested a stage IIIb lymphoma. Chemotherapy was given, but the disease still progressed and the patient died 4 months after diagnosis. Primary adrenal lymphoma should be considered in the differential diagnosis of Addison's disease, even if only slight enlargement of the adrenal glands is found initially.
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PMID:Adrenal lymphoma and Addison's disease: report of a case. 1263 19

Anorexia is one of the common symptoms caused by various psychiatric disorders. Increasing evidence indicates that neuroleptics can induce weight gain, obesity, and diabetes mellitus. However, the mechanisms underlying these conditions have not been fully elucidated. In this review, we describe molecular neuroanatomic aspects of current biology of energy homeostasis that would help to address the psychiatric issues noted above, focusing on the central leptin/melanocortin system. An adipocyte-derived hormone, leptin acts on the arcuate hypothalamic nucleus (Arc) to inhibit feeding behavior and simultaneously to promote energy expenditure. Leptin activates Arc neurons producing alpha-melanocyte-stimulating hormone (alpha-MSH) and inhibits those producing agouti-related protein (AgRP). alpha-MSH is an endogenous agonist for the melanocortin-4 receptor (MC4-R) that is expressed exclusively in the central nervous system (CNS), whereas AgRP acts as a MC4-R antagonist. It is also established that MC4-R blockade produces an over-eating/obesity syndrome in rodents and humans. Thus, MC4-R-expressing neurons are downstream targets of leptin. Of interest, MC4-R-positive neurons densely populate in CNS sites critical for energy homeostasis and associated with psychiatric disorders, including the paraventricular hypothalamic nucleus and central amygdaloid nucleus. In addition, Arc alpha-MSH neurons receive serotonergic inputs from raphe neurons. Finally, an AgRP gene polymorphism has been associated with anorexia nervosa. These findings suggest that the central melanocortin system is a target for psychiatry.
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PMID:[Psychiatric disorders and neural mechanisms underlying energy intake and expenditure: a review]. 1465 25

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.
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PMID:Appetite and cancer-associated anorexia: a review. 1577 9

We recently reported that intracerebroventricular infusions of ANG II decreased food intake and increased energy expenditure in young rats. The aim of the present study was to determine if intracerebroventricular ANG II has similar effects in adult rats. The time course of the effect was also investigated with the idea that at earlier time points, a potential role for increased hypothalamic expression of corticotropin-releasing hormone (CRH) in the anorexia could be established. Finally, the contribution of ANG II-induced water drinking to the decrease in food intake was directly investigated. Rats received intracerebroventricular saline or ANG II using osmotic minipumps. Food intake, water intake, and body weight were measured daily. Experiments were terminated 2, 5, or 11 days after the beginning of the infusions. ANG II (approximately 32 ng.kg(-1).min(-1)) produced a transient decrease in food intake that lasted for 4-5 days although body weight continued to be decreased for the entire experiment most likely due to increased energy expenditure as evidenced by increased uncoupling protein-1 mRNA expression in brown adipose tissue. At 11 and 5 days, the expression of CRH mRNA was decreased. At 2 days, CRH expression was not suppressed even though body weight was decreased. The decrease in food intake and body weight was identical whether or not rats were allowed to increase water consumption. These data suggest that in adult rats ANG II acts within the brain to affect food intake and energy expenditure in a manner that is not related to water intake.
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PMID:Effect of intracerebroventricular angiotensin II on body weight and food intake in adult rats. 1511 28


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