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)

Aging, as well as some frequently associated pathological conditions (depression, dementia, Alzheimer's disease, etc.), has been shown to have a profound impact on the normal functioning of the hippocampus-hypothalamo-pituitary-adrenocortical axis system. The hypothalamo-pituitary-adrenocortical axis in the aged rat is characterized by an increase in the basal level of circulating corticosterone, an impaired ability to recover from the adrenocortical stress response, and a reduced sensitivity to the dexamethasone suppression test. All these alterations may arise from a reduced hippocampal negative feedback control of the axis, as suggested by the age-dependent loss of hippocampal adrenocorticoid receptors. Among the hypothalamic corticotropin secretagogues, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) are considered the main physiological mediators of hypothalamic control of ACTH release. Thus, we have investigated the dynamic and the temporal course of the adrenocortical response to CRH and AVP in the aged rat. Freely moving jugular-catheterized male Sprague-Dawley rats (3- and 24-month-old) were injected with CRH (0.5, 0.05 and 0.01 microgram/kg i.v.), or AVP (1.0, 0.1 and 0.05 microgram/kg i.v.), or CRH and AVP in combination. In addition, adrenocortical sensitivity to corticotropin has been studied by injecting ACTH (10 ng/kg i.v.). Our study has (1) indicated that the response to ACTH secretagogues is dampened with aging, and (2) shown in the aged rat a slower recovery. Moreover, the results had confirmed the age-dependent increase in the basal level of corticosterone in the rat, and shown no age-related differences in the glucocorticoid response to ACTH.
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PMID:Reduced glucocorticoid response to corticotropin secretagogues in the aged Sprague-Dawley rat. 756 36

We studied interleukin-1 beta (IL-1 beta), beta 2-microglobulin (beta 2-m), beta-endorphin, substance P, neuropeptide Y and somatostatin concentrations in the cerebrospinal fluid of 13 patients with dementia of the Alzheimer type (DAT), 13 patients with multi-infarct dementia (MID) and 15 age-matched control subjects. Substance P was significantly lower in DAT than in controls (P < 0.05), as well as somatostatin in DAT as compared to both controls (P < 0.01) and MID (P < 0.05), whereas beta 2-m was higher in DAT than in controls (P < 0.01). Neuropeptide Y, beta-endorphin and IL-1 beta showed similar concentrations in the three groups studied. A significantly positive correlation was observed between IL-1 beta and substance P (r = 0.79, P < 0.01) and somatostatin (r = 0.75, P < 0.05) in DAT, which was not observed in MID. In addition, beta 2-m showed a negative correlation with IL-1 beta (r = -0.73, P < 0.05) in DAT, and age correlated negatively with IL-1 beta in controls and MID, but positively in DAT. Therefore, these results support the idea that an altered relationship may exist in Alzheimer's disease between the nervous and immune system.
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PMID:Relationship of interleukin-1 beta and beta 2-microglobulin with neuropeptides in cerebrospinal fluid of patients with dementia of the Alzheimer type. 769 56

In an attempt to find if a disturbance in the function of the feedback regulation of the hypothalamic-pituitary-adrenal axis is an early feature in Alzheimer's disease (AD), 35 outpatients (mean age 76.8 years) with a mild to moderate AD were compared to 20 controls (mean age 73.8 years) in their response to different doses of dexamethasone. After 0.5 mg dexamethasone, serum cortisol levels were significantly less suppressed in patients with early AD (p = .03) and these patients were significantly more often dexamethasone nonsuppressors (serum cortisol > or = 138 nmol/l) than controls (14/35 vs. 2/20; p = .03). Nonsuppression to 1 mg dexamethasone did not differ between groups (2/35 vs. 0/20). Plasma adrenocorticotropin levels were significantly lower in patients with Alzheimer's disease (n = 16) after 0.5 mg as well as after 1.0 mg dexamethasone (p = .01 and p < .001, respectively). The relationship between cortisol resistance to dexamethasone suppression and pathophysiology of AD is discussed.
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PMID:A subtle disturbance in the feedback regulation of the hypothalamic-pituitary-adrenal axis in the early phase of Alzheimer's disease. 789 39

Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD.
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PMID:Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection. 791 13

The circadian pattern of melatonin and cortisol secretion was evaluated in two groups of elderly subjects (aged 66-90 years), one with Alzheimer's type of multiinfarct dementia (n = 27) and the other without cognitive impairment (n = 16); 13 clinically healthy women aged 20 to 30 years were chosen as controls. All demented patients had severe mental impairment, corresponding to stage 6 of the Global Deterioration Scale. All subjects, either young or aged, were studied as in-patients and were well synchronized with respect to meal timing, diurnal activity and nocturnal rest. At the population mean cosinor analysis (Halberg, 1969) both melatonin and cortisol circadian rhythms reached statistical significance in the three groups of subjects. However, the melatonin circadian profile was clearly flattened in the two groups of elderly subjects by comparison with young controls, due to the selective impairment of melatonin nocturnal secretion. In both elderly groups, but particularly in demented patients, plasma cortisol levels were significantly higher by comparison to young controls, particularly at evening and night time. A significant direct relationship linked the subjects' age and the nadir values of plasma cortisol. Furthermore, the sensitivity of the hypothalamo-pituitary-adrenal axis to dexamethasone (DXM) suppression test (1 mg orally at 2300) was significantly reduced in both elderly groups, and especially in old demented patients, by comparison with young controls. Finally, plasma cortisol response to pulse i.v. injection of a small dose of synthetic corticotropin (Synacthen 2,500 ng) was significantly higher and more prolonged in old demented patients than in mentally healthy old subjects and in young controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chrono-neuroendocrinological aspects of physiological aging and senile dementia. 792 32

Recent studies on experimental animals showed that long term activation of the hypothalamo-pituitary-adrenal axis is associated with increased vasopressin (AVP) colocalization in paraventricular corticotropin-releasing hormone (CRH) neurons. In the present study we estimated the fraction of CRH neurons in which AVP is colocalized by double label immunocytochemistry in hypothalami of 10 control subjects of 21-91 years of age and 10 age-matched Alzheimer patients. CRH neurons in the paraventricular nucleus (PVN) of Alzheimer patients and control subjects showed similar age dependent increases in AVP colocalization. Based on this parameter, it seems that CRH neurons of Alzheimer patients are not overactivated as compared to age-matched controls, but e.g. changes in m-RNA for CRH should still be established.
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PMID:Similar age related increase of vasopressin colocalization in paraventricular corticotropin-releasing hormone neurons in controls and Alzheimer patients. 804 11

It has been hypothesized that the corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) become hyperactive with age, and even more so in Alzheimer's disease. This hyperactivity could be due to an increased production of CRH per neuron, or an increased number of PVN neurons producing CRH, or both. As a first step in elucidating which of these biological mechanisms might be operative, we have estimated the absolute number of CRH immunoreactive neurons in the PVN of 10 human control subjects between 36 and 91 years of age and 10 Alzheimer patients between 40 and 97 years of age. CRH neurons were immunocytochemically detected in 6 microns paraffin sections with the aid of a highly specific monoclonal antibody to CRH. The antibody signal was amplified by the biotin-streptavidin and alkaline phosphatase methods. The absolute number of CRH neurons in the PVN was obtained by multiplying the number of CRH neurons in a unit volume (NV) by the total volume of the PVN. Two different methods were used to estimate the NV: an unfolding method and a disector method (about three times more time-consuming). Compared to the disector, the unfolding method consistently yielded a lower cell number for all patients by 38% (+/- 2.8%; mean +/- SEM). However, both methods yielded an increase in the absolute number of CRH neurons in control and Alzheimer patients with age. No statistically significant difference in the absolute number of CRH neurons was found between control and Alzheimer patients with both methods. The age-dependent increase in the absolute number of CRH neurons within the PVN of both control and Alzheimer patients is interpreted as a sign of activation of the CRH neurons with age.
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PMID:Age-related increase in the total number of corticotropin-releasing hormone neurons in the human paraventricular nucleus in controls and Alzheimer's disease: comparison of the disector with an unfolding method. 813 71

Alterations of neuroendocrinological indices determined by the impaired regulating effects of cholinergic neurotransmission have been described in primary dementia. In this study we have evaluated the effects of acetylcholinesterase inhibition by pyridostigmine on growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7 patients with primary degenerative dementia and in 8 sex- and age-matched controls. Demented subjects showed higher cortisol basal levels and lower ACTH levels than controls. Pyridostigmine increased the GH response to GHRH in both groups, the effect being significantly enhanced in patients. An increase of ACTH and cortisol levels was found in both groups after pyridostigmine and CRH administration. Pyridostigmine pretreatment significantly increased the ACTH response to CRH in controls but not in patients. The obtained data may indicate that a muscarinic receptor upregulation and an impairment of somatostatinergic function are operative in the regulation of GH secretion in dementia. An underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the responses of ACTH and cortisol to CRH in this disorder.
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PMID:Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone-releasing hormone on the pituitary-adrenal axis and on growth hormone secretion in dementia. 827 99

In an acute trial, three different dosages (60, 300, and 600 micrograms) of the endocrinologically inert but behaviorally active corticotropin 4-9 (ACTH4-9) fragment ebiratide were given to three patients with clinically probable Alzheimer's disease and five patients with a major depressive episode who were psychomotorly retarded. The drug was given intravenously in a double-blind, placebo-controlled, crossover design, and cognitive as well as psychopathologic assessments were carried out predrug and postdrug treatment. In summary, no adverse effect of the ACTH fragment was detected. In this explorative study, none of the patients improved cognitively, as measured by neuropsychologic testing. However, all patients, regardless of underlying disorder, reported a decrease of the feeling of tiredness or loss of energy, respectively. They felt more vigorous and alert. This occurred after any of the three doses of ACTH4-9, but not after placebo. In concert with reports from other studies, it is concluded that the ACTH4-9 fragment ebiratide may have activating properties in humans. However, given acutely, it does not seem to have antidementia or antidepressive efficacy.
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PMID:Behavioral effects of a synthetic corticotropin 4-9 analog in patients with depression and patients with Alzheimer's disease. 839 47

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, plasma levels of ACTH and cortisol, and serum levels of phospholipid and its fractions were determined in samples taken simultaneously from patients with senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID) or dementia following a cerebrovascular accident (CVD), and the borderline-to-normal control subjects. CRH levels in CSF were significantly reduced in patients with SDAT and CVD but not with MID compared to the borderline-to-normal controls. ACTH levels in CSF were significantly reduced in SDAT compared to MID. The levels of circulating lecithin (phosphatidyl-choline) were depressed in a similar fashion to the levels of CRH in CSF in the SDAT patients and the group of severe dementia. Dementia and its severity did not affect the morning plasma levels of ACTH and cortisol. CSF CRH was positively correlated with CSF ACTH, while CSF ACTH was negatively correlated with plasma cortisol. No significant correlations were found between serum lecithin and CSF CRH or ACTH. These findings suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) the CRH system and the ACTH system correlate with each other within the brain; 3) CSF ACTH is subject to the feedback inhibition by circulating cortisol; and 4) in the SDAT patients and the severe dementia group CSF CRH and serum lecithin are reduced probably via independent mechanisms.
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PMID:Cerebrospinal fluid corticotropin-releasing hormone and ACTH, and peripherally circulating choline-containing phospholipid in senile dementia. 839 71


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