UMLS:C0020505 - FACTA Search

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Query: UMLS:C0020505 (hyperphagia)
6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore whether possible differences in central nervous system neuromodulators contribute to the differential presentation of affective symptomatology in Cushing's disease and major depression, we examined the levels of immunoreactive CRH and ACTH in the cerebrospinal fluid (CSF) of 11 patients with Cushing's disease, a patient with ectopic ACTH secretion, 34 patients with major depression, and 60 healthy subjects. We elected to measure these peptides not only because both are classically involved in pituitary-adrenal regulation, but also because their primarily arousal-producing and anorexigenic behavioral effects in experimental animals suggest that they may play a role in the symptom complex of depressive syndromes. We also explored whether the CSF levels of these peptides were more helpful in determining the often difficult differential diagnosis between major depression and Cushing's disease than the plasma ACTH response to ovine CRH, a currently used but somewhat insensitive laboratory means of distinguishing these disorders. CSF levels of immunoreactive CRH and ACTH were significantly lower in Cushing's disease patients [21.9 +/- 2.7 and 15.4 +/- 1.8 pg/mL, (mean +/- SEM), respectively] compared to patients with major depression [38.4 +/- 2.3 pg/mL (P less than 0.01) and 24.5 +/- 1.6 pg/mL (P less than 0.01), respectively] and controls [38.4 +/- 1.6 pg/mL (P less than 0.001) and 26.3 +/- 1.1 pg/mL (P less than 0.001), respectively]. The coexistence of high plasma ACTH and low CSF ACTH in Cushing's disease yielded a CSF/plasma ACTH ratio consistently less than that in depressed patients, with only 2 of 31 subjects comprising both groups showing values that overlapped. In contrast, 9 of the combined patients showed ACTH responses to ovine CRH that overlapped. These data suggest that differences in centrally directed CRH secretion may account for the differential presentation of the dysphoric syndromes seen in major depression and Cushing's disease. Hence, the classic form of major depression (melancholia), is often associated with evidence of pathological hyperarousal, such as intense anxiety, sleeplessness, and anorexia, while that of Cushing's disease is associated with evidence of pathological hyperarousal, including hyperphagia, fatigue, and inertia. Moreover, measurement of the CSF/plasma ACTH ratio may serve as a clinically useful adjunct to the ovine CRH stimulation test and other laboratory measures in determining the differential diagnosis between major depression and Cushing's disease.
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PMID:Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications. 199 96

CRH has been shown to produce increased locomotion, arousal, and anorexia in experimental animals. A deficiency of CRH in patients with seasonal affective disorder could contribute to the characteristic lethargy, hypersomnia, and hyperphagia characteristic of this illness. To test this hypothesis, we studied basal plasma ACTH and cortisol levels and their responses to ovine CRH in controls and depressed patients with seasonal affective disorder before and after light treatment. Untreated seasonal affective disorder patients showed normal basal plasma cortisol and ACTH levels, but their responses to CRH tended to be delayed and were significantly reduced. When patients were studied after 9 days of light treatment, a significant increase in plasma ACTH and cortisol responses to CRH was observed. Our findings in untreated patients with seasonal affective disorder are similar to those in patients with Cushing's disease 2 weeks after transsphenoidal hypophysectomy, who uniformly show sustained suppression of their CRH neuron because of long-standing hypercortisolism. This findings suggest that the CRH neuron of patients with seasonal affective disorder is hypofunctional. We postulate that the clinical symptomatology in patients with seasonal affective disorder could reflect deficient activity of this important arousal-producing system.
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PMID:Abnormal pituitary-adrenal responses to corticotropin-releasing hormone in patients with seasonal affective disorder: clinical and pathophysiological implications. 185 Nov 85

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression. Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression. In a series of studies, commencing in patients with Cushing's disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide. In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.
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PMID:Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. 859 44

The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.
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PMID:The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. 989 54

Various aspects of the complex spatio-temporal patterning of hypothalamic signaling that leads to the development of synchronized nocturnal feeding in the rat are critically examined. Undoubtedly, as depicted in Fig. 7, a distinct ARN in the hypothalamus is involved in the control of nocturnal appetite. At least four basic elements operate within this ARN. These are: 1) A discrete appetite-driving or orexigenic network of NPY, NE, GABA, GAL, EOP, and orexin transduces and releases appetite-stimulating signals. 2) Similarly, anorexigenic signal-producing pathways (e.g., CRH, GLP-1, alpha MSH, and CART) orchestrate neural events for dissipation of appetite and to terminate feeding, possibly by interrupting NPY efflux and action at a postsynaptic level within the hypothalamus. It is possible that some of these may represent the physiologically relevant "off" switches under the influence of GABA alone, or AgrP alone, or in combination with NPY released from the NPY-, GABA-, and AgrP-coproducing neurons. 3) Recent evidence shows that neural elements in the VMN-DMN complex tonically restrain the orexigenic signals during the intermeal interval; the restraint is greatly aided by leptin's action via diminution of orexigenic (NPY) and augmentation of anorexigenic (GLP-1, alpha MSH, and CART) signals. Since interruption of neurotransmission in the VMN resulted in hyperphagia and development of leptin resistance, it seems likely that the VMN is an effector site for the restraint exercised by leptin. The daily rhythms in leptin synthesis and release are temporally dissociable because the onset of daily rise in leptin gene expression in adipocytes precedes that in leptin secretion. Nevertheless, these rhythms are in phase with daily ingestive behavior because the peak in circulating leptin levels occurs during the middle of the feeding period. These observations, coupled with the fact that circulating levels of leptin are directly related to adiposity, pose a new challenge for elucidating the precise role of leptin in daily patterning of feeding in the rat. 4) A neural timing mechanism also operates upstream from the ARN in the daily management of energy homeostasis. Although the precise anatomical boundaries are not clearly defined, this device is likely to be composed of a group of neurons that integrate incoming internal and external information for the timely onset of the drive to eat. Evidently, this network operates independently in primates, but it is entrained to the circadian time keeper in the SCN of rodents. Apart from its role in the onset of drive to eat, the circadian patterns of gene expression of NPY, GAL, and POMC denote independent control of the timing device on the synthesis and availability for release of orexigenic signals. The VMN-DMN-PVN complex is apparently an integrated constituent of the timing mechanism in this context, because lesions in each of these sites result in loss of regulated feeding. The accumulated evidence points to the PVN and surrounding neural sites within this framework as the primary sites of release and action of various orexigenic and anorexigenic signals. A novel finding is the identification of the interconnected wiring of the DMN-mPVN axis that may mediate leptin restraint on NPY-induced feeding. The chemical phenotypes of leptin and NPY target neurons in this axis remain to be identified. These multiple orexigenic and anorexigenic pathways in the hypothalamic ARN appear to represent redundancy, a characteristic of regulated biological systems to provide a "fail-safe" neural mechanism to meet an organism's constant energy needs for growth and maintenance. Within this formulation, the coexisting orexigenic signals (NPY, NE, GAL, GABA, and AgrP) represent either another level of redundancy or it is possible that these signals operate within the ARN as reinforcing agents to varying degrees under different circumstances. (ABSTRACT TRUNCATED)
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PMID:Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. 1004 74

Ten dogs with pituitary-dependent hyperadrenocorticism (PDH) received 2 mg/kg of L-Deprenyl once daily for 6 months. Monthly patient assessment consisted of evaluation of the owner's daily observation protocol, a standardized owner questionnaire, physical examination, CBC, biochemical profile, determination of the urine cortisol/creatinine ratio (UC/C), low-dose dexamethasone suppression (LDDS) test, corticotropin releasing hormone (CRH) test, and adrenal ultrasonography. At the beginning and the end of the study, an adrenocorticotropic hormone (ACTH) stimulation test and computed tomography also were performed. Two dogs developed neurologic signs and 2 dogs developed acute pancreatitis. An increase in activity, decrease in polyphagia, and decrease in panting were reported by 6, 4, and 2 owners, respectively. Seven owners believed that water intake decreased, but this was confirmed in only 3 dogs. Water intake increased in 2 dogs and remained unchanged in 5 dogs. The condition of the hair coat and skin improved in 2 dogs, worsened in 3, and remained unchanged in 5. Urine specific gravity, urine osmolality, ACTH test results, UC/C, and adrenal gland size did not change significantly throughout the study. In 4 of 8 dogs, LDDS was abnormal at the start of the study but normal at the end of the study, and in 2 dogs, the opposite occurred. Marked individual variation was noted in the CRH test, with a tendency for smaller increases in ACTH toward the end of the study. A marked increase in hypophyseal tumor size occured in 4 dogs. Treatment with L-Deprenyl resulted in improvement, deterioration, and stagnation of clinical signs in 2, 4, and 4 dogs, respectively. The results of this study indicate that L-Deprenyl cannot be recommended as the sole treatment for canine PDH.
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PMID:The efficacy of L-Deprenyl in dogs with pituitary-dependent hyperadrenocorticism. 1044 18

Lactation is a physiological model for studying how the hypothalamus integrates peripheral signals, such as sensory signals (suckling stimulus) and those denoting energy balance (leptin), to alter hypothalamic function regulating food intake/energy balance and reproduction. The characteristics of food intake/energy balance during lactation are extreme hyperphagia, coupled with negative energy balance. The arcuate nucleus Neuropeptide Y (ARH-NPY) system is activated by: (1) brainstem projections specifically activated by the suckling stimulus, and (2) the decrease in leptin in response to the metabolic drain of milk production. NPY neurons from the ARH make direct contact with GnRH neurons and with CRH neurons in the PVH. NPY neurons also make contact with orexin and MCH neurons in the LHA, which, in turn, make contacts with GnRH neurons. Thus, the ARH-NPY system provides a neuroanatomical framework by which to integrate changes in food intake/energy with the regulation of cyclic reproductive function.
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PMID:Integration of the regulation of reproductive function and energy balance: lactation as a model. 1212 5

Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the need to restrain overeating under natural conditions, is doubtful. We have previously shown that CRH-deficient (Crh(-/-)) mice have glucocorticoid insufficiency and lack the fasting-induced increase in glucocorticoid, a hormone important in stimulating leptin synthesis and secretion. We hypothesized that these mice might have low circulating leptin. Indeed, Crh(-/-) mice exhibited no diurnal variation of leptin, whereas normal littermates showed a clear rhythm, and their leptin levels were lower than their counterparts. A continuous peripheral CRH infusion to Crh(-/-) mice not only restored corticosterone levels, but it also increased leptin expression to normal. Surprisingly, 36 h of fasting elevated leptin levels in Crh(-/-) mice, rather than falling as in normal mice. This abnormal leptin change during fasting in Crh(-/-) mice was corrected by corticosterone replacement. Furthermore, Crh(-/-) mice lost less body weight during 24 h of fasting and ate less food during refeeding than normal littermates. Taken together, we conclude that glucocorticoid insufficiency in Crh(-/-) mice results in impaired leptin production as well as an abnormal increase in leptin during fasting, and propose that the fast-induced physiological reduction in leptin may play an important role to stimulate food intake during the recovery from fasting.
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PMID:Impaired leptin expression and abnormal response to fasting in corticotropin-releasing hormone-deficient mice. 1503 10

Chronic rapid eye movement (paradoxical) sleep deprivation (REM-SD) of rats leads to two conspicuous pathologies: hyperphagia coincident with body weight loss, prompted by elevated metabolism. Our goals were to test the hypotheses that 1) as a stressor, REM-SD would increase CRH gene expression in the hypothalamus and that 2) to account for hyperphagia, hypothalamic gene expression of the orexigen neuropeptide Y (NPY) would increase, but expression of the anorexigen proopiomelanocortin (POMC) would decrease. Enforcement of REM-SD of adult male rats for 20 d with the platform (flowerpot) method led to progressive hyperphagia, increasing to approximately 300% of baseline; body weight steadily declined by approximately 25%. Consistent with changes in food intake patterns, NPY expression rapidly increased in the hypothalamic arcuate nucleus by d 5 of REM-SD, peaking at d 20; by contrast, POMC expression decreased progressively during REM-SD. CRH expression was increased by d 5, both in mRNA and ability to detect neuronal perikaryal staining in paraventricular nucleus with immunocytochemistry, and it remained elevated thereafter with modest declines. Taken together, these data indicate that changes in hypothalamic neuropeptides regulating food intake are altered in a manner consistent with the hyperphagia seen with REM-SD. Changes in CRH, although indicative of REM-SD as a stressor, suggest that the anorexigenic actions of CRH are ineffective (or disabled). Furthermore, changes in NPY and POMC agree with current models of food intake behavior, but they are opposite to their acute effects on peripheral energy metabolism and thermogenesis.
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PMID:Changes in hypothalamic corticotropin-releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats. 1621 Mar 72

Human (visceral) obesity is associated with alterations hypothalamus-pituitary-adrenal (HPA) axis functioning. It is however not completely clear whether the HPA axis is causally or co-incidentally related to (visceral) obesity. This review summarizes supporting data of an involvement of the HPA axis in the development of (visceral) obesity. First, several DNA polymorphisms related to HPA axis functioning are correlated to the development of obesity. Second, chronic elevation of circulatory glucocorticoid concentrations, as in Cushing's disease, results in increased abdominal adiposity. Third, (visceral) obesity is associated with a diminished capacity of cortisol to suppress its own secretion. HPA axis functioning might affect energy balance through affecting energy intake. Both CRH and cortisol influence physiological, central mechanisms involved in the regulation of food intake. Still, general activation of the HPA axis has shown to have inconsistent effects on food intake in humans. This inconsistency may partially be explained by gender differences, individual differences in the functioning of the HPA axis, as well as differences in attitude towards eating. In particular, women with high scores on dietary restraint are prone to stress-induced hyperphagia. Dietary restraint scores, in turn, are positively correlated to basal and dexamethasone-suppressed cortisol levels, indicating a complex dual relationship between stress, HPA axis functioning, attitude towards eating and the risk for stress-induced hyperphagia. In the Western society, with chronically high ambient levels of stress and the availability of high caloric foods, this relationship may imply a risk for the development of (visceral) obesity and the metabolic syndrome.
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PMID:The hypothalamic-pituitary-adrenal-axis in the regulation of energy balance. 1827 77

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