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

Suicidal behavior has been associated with hypothalamic-pituitary-adrenal overactivity in humans, as measured by increased corticosteroid secretion. To investigate whether this overactivity is reflected at the pituitary level, we have studied the localization of pro-opiomelanocortin (POMC) mRNA, and glucocorticoid receptor (GR) mRNA, in human anterior pituitaries, and quantified these messages relative to controls. Pituitaries from 7 suicide victims and 11 cardiac deaths were sectioned into 10-microns slides, stained with thionin and processed for in situ hybridization using a riboprobe complementary to human POMC mRNA. To correct for possible postmortem cell loss, hybridization with P1B15, a cDNA complementary to rat cyclophillin mRNA, was used in adjacent sections. POMC mRNA containing cells were found to be localized in clusters and were highly associated with corticotropin-releasing hormone (CRH) receptors. In contrast, GR mRNA containing cells were distributed through the pituitary, although areas of increased density were associated with POMC mRNA cells. Quantification with a computerized image analysis system revealed a 25% increase in POMC message in suicide victims. Analysis of the corticotrophic cell clumps showed that the suicide victims had higher POMC mRNA density per cell (p = 0.04) and larger corticotrophic cell size (p = 0.04) than the cardiac death victims. No differences in GR mRNA were detected between the two groups, although GR and POMC mRNA levels were highly and significantly correlated (r = 0.8, p < 0.001). There were no differences in P1B15 message between the two groups. We conclude that in situ hybridization is a useful tool to study gene regulation in human neuroendocrine tissue and that suicide victims show evidence of chronic hypothalamic-pituitary-adrenal axis activation.
 ...
PMID:Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims. 133 53

Corticotropin-releasing hormone (CRH), somatostatin (SOM), delta-sleep-inducing peptide (DSIP), neuropeptide Y (NPY), beta-endorphin (beta-END), and vasopressin (AVP), which are regarded as being involved in the HPA-regulation were investigated in lumbar CSF of 44 suicide attempters. The patients were diagnosed according to the DSM-III-R, and rated with the MADRS. The neuropeptides were compared with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF and with post-dexamethasone plasma cortisol. We found strong correlations between CRH and the peptides SOM and beta-END. The latter also correlated positively with SOM. There were no differences between men and women. Patients with major depressive disorders had significantly lower SOM, CRH, and DSIP than other patients. Both SOM and beta-END correlated negatively with post dexamethasone plasma cortisol in all patients. We found no significant relationships between neuropeptides and CSF 5-HIAA. Patients who had made previous suicide attempts had significantly lower CRH than those who had not. No other significant associations between neuropeptides and suicidal subgroups of patients appeared, and there was no indication of specific neuropeptide patterns in patients who later completed suicide. Intercorrelations of some neuropeptides and low SOM and DSIP in major depressed patients are findings in line with those by others.
 ...
PMID:HPA-related CSF neuropeptides in suicide attempters. 137 70

Hypothalamic-pituitary-adrenal (HPA) axis function was examined in relation to suicidal behavior in depression. There were no significant differences between depressed patients who had or had not attempted suicide for either cerebrospinal fluid concentrations of corticotropin-releasing hormone, plasma cortisol levels predexamethasone or postdexamethasone, or for urinary-free cortisol outputs. However, depressed patients who had made a violent suicide attempt had significantly higher 4 PM and maximum postdexamethasone plasma cortisol levels, and significantly more of them were cortisol nonsuppressors than patients who had made nonviolent suicide attempts. A 5-year follow-up was carried out. There were no significant differences on indices of HPA function between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted suicide. These results suggest the possibility that dysregulation of the HPA axis may be a determinant of violent suicidal behavior in depression.
 ...
PMID:Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression. 145 Feb 95

There are indications to suggest a relationship between low levels of 5-hydroxy-indoleacetic acid (5HIAA) in the cerebrospinal fluid and suicidal behavior. Many depressed patients show an elevated cortisol secretion. As beta-endorphin is derived from the same precursor as ACTH, it is expected that plasma beta-endorphin levels will also rise in depressed patients. We report here a case of severe depression with diurnal variation who showed low CSF 5HIAA prior to his suicide. In contrast, his catecholamine metabolites were 50% above the mean values of other depressed patients. Hormonal measurements, however, showed low cortisol, prolactin and beta-endorphin levels.
 ...
PMID:Diurnal rhythms of plasma cortisol, beta-endorphin and prolactin, and cerebrospinal fluid amine metabolite levels before suicide. Case report. 243 87

Several neurochemical correlates of suicide were recently detected. Some authors found increased disorders in the hypothalamic-pituitary-adrenal (HPA) and -thyroid (HPT) axes and disturbances in serotonergic neurotransmission in suicidal patients. In order to investigate the biological correlates of suicidal ideation, we measured the following: basal thyrotropin-secreting hormone (TSH), free thyroxine (FT4), pre- and postdexamethasone cortisol, adrenocorticotropic hormone (ACTH) levels, the circulating concentrations of total L-tryptophan (L-TRP) and the ratio between L-TRP and competing amino acids (CAA). The subjects were 17 suicidal and 17 nonsuicidal major depressed females matched for age and severity of illness. We found no significant differences in any of the above-mentioned biological data between patients with suicidal ideation and those without.
 ...
PMID:Hypothalamic-pituitary-adrenal and -thyroid axis dysfunctions and decrements in the availability of L-tryptophan as biological markers of suicidal ideation in major depressed females. 254 71

Male Wistar-Furth rats bearing the transplantable LTW(m) Leydig cell tumor have elevated serum estradiol (E2) concentrations. We measured the ability of these tumors to aromatize testosterone (T) to E2 by two methods. First, tumor minces were incubated with [7-3H]T, and the resultant [3H]E2 and [3H]estrone were purified and measured. In addition, tumor cell cultures were incubated with [1 beta-3H]T, and the resultant [3H]H2O was determined as a measure of aromatization. Tumor minces aromatized more actively than normal rat testicular tissue (3.30 +/- 0.15% of the T added was converted to E2 by the tumor vs. 0.30 +/- 0.25% by normal testis). Most of the aromatizing actitivity was localized to the microsomes. Using cell cultures the maximum velocity was 6.1 pmol/h X 5 X 10(5) cells, and the Km was 98 nM. In neither minces nor cell cultures were we able to show stimulation of aromatization with hCG, (Bu)2cAMP, or phorbol esters, although we could show stimulation by these agents in normal testicular cells. We were unable to inhibit the aromatase activity with human beta-endorphin or stimulate it with naloxone. However, we were able to inhibit the aromatase activity with 4-hydroxy-4-androstene-3,17-dione. We conclude that the LTW(m) rat Leydig cell tumor has an active autonomous aromatase system that is not responsive to compounds affecting the adenylate cyclase-cAMP system. It can be inhibited by 4-hydroxy-4-androstene-3,17-dione, a competitive-suicide inhibitor of the aromatase enzyme(s).
 ...
PMID:Aromatase activity in a rat Leydig cell tumor. 303 Jul 2

In a previous study, increased weight of the adrenal glands was found in a small group of persons who committed violent suicides. This finding was confirmed in our study, which comprised a group of 42 suicide cases and 37 control cases. Further analysis with special consideration toward a "relative adrenal weight" (weight/body surface) revealed that a relative combined adrenal weight >6 g/m2 may be a morphologic sign of a depressive disorder prior to death if no other disease with a known effect on the adrenals is present. These results are consistent with clinical computed tomographic findings of enlarged adrenals in depressed patients. In all suicide cases the police records were reviewed and a postmortem psychiatric diagnosis conducted to investigate whether a correlation between adrenal weight and the "severity" of depression or type of psychiatric disorder exists. In thirteen cases, psychiatric treatment prior to death was known, and a postmortem severity score of depressive disease was formed. No influence of this score or the postmortem diagnosis on the adrenal weight, however, could be detected. Also, the increase in weight of adrenal glands could not be explained by a suspected or proven preceding drug therapy or use. The effect on the pituitary-adrenal-axis by depressive disorders and changes in serotonin metabolism have been investigated repeatedly; mainly reported are increased levels of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in the depressive interval, which may lead to a growth of the adrenal glands.
 ...
PMID:Weight of adrenal glands may be increased in persons who commit suicide. 953 97

Several lines of evidence suggest a dysregulation of the adrenocortical (HPA) system with hypersecretion of CRH is associated with suicidal behavior. However, controversial results have emerged from the determination of corticotropin-releasing hormone (CRH) concentrations in the lumbar cerebrospinal fluid (CSF) of suicide attempters probably due to methodological differences. We simultaneously measured CRH concentrations in the CSF and in the plasma of 41 psychiatric in-patients with different diagnoses (affective disorder, schizophrenia, personality disorders, adjustment disorder, substance abuse) and eight neurological control subjects. We also measured plasma cortisol concentrations because data from animal experiments suggest that cortisol may influence CSF CRH concentrations. The major finding was that patients who attempted suicide prior to admission had significantly lower CSF CRH concentrations than psychiatric patients without suicidal behavior. CRH concentrations were significantly higher in the CSF than in plasma in both, psychiatric patients and neurological control subjects. There was no significant difference between suicide attempters and patients with acute suicidal ideations. The latter group showed a trend towards lower CSF CRH concentrations compared with the neurological control subjects. Patients with affective disorder alone as well as patients with multiple diagnoses, but not schizophrenic patients, showed significantly lower CSF CRH concentrations than neurological control subjects. Plasma CRH and plasma cortisol concentrations did not differ among diagnostic groups or between suicide attempters vs. non-attempters. Further studies with more homogeneous samples, drug-free patients and with simultaneous assessment of various parameters of the HPA system are warranted.
 ...
PMID:Decreased corticotropin-releasing hormone (CRH) concentrations in the cerebrospinal fluid of eucortisolemic suicide attempters. 1128 50

Increased plasma arginine vasopressin (AVP) concentrations have been reported in depressed suicide attempters. Plasma AVP is primarily produced by the magnocellular system in response to increased plasma osmolality, and central AVP may be independently regulated. In the present study we investigated cerebrospinal fluid (CSF) and plasma AVP concentrations in depressed patients and controls. Nineteen drug-free depressed psychiatric inpatients (nine suicide attempters) and nine neurological control subjects underwent lumbar puncture and psychiatric evaluation. CSF and plasma concentrations of AVP, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol were assayed. In 15 depressed patients (eight suicide attempters), the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed to examine the hypothalamic-pituitary-adrenocortical (HPA) system. There were no differences between depressed subjects and controls in all parameters measured. Suicide attempters did not differ from nonattempters. In depressed patients, plasma AVP correlated positively with cortisol. There was no relationship between CSF AVP and monoamine metabolites in CSF.
 ...
PMID:Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results. 1220 67

A number of clinical investigations and postmortem brain studies have provided evidence that excessive corticotropin-releasing hormone (CRH) secretion and neurotransmission is involved in the pathophysiology of depressive illness, and several studies have suggested that the hyperactivity in CRH neurotransmission extends beyond the hypothalamus involving several extra-hypothalamic brain regions. The present study was designed to test the hypothesis that CRH levels are increased in specific brainstem regions of suicide victims with a diagnosis of major depression. Frozen tissue sections of the pons containing the locus coeruleus and caudal raphe nuclei from 11 matched pairs of depressed suicide and control male subjects were processed for radioimmunocytochemistry using a primary antiserum to CRH and a ([125])I-IgG secondary antibody. The optical density corresponding to the level of CRH-immunoreactivity (IR) was quantified in specific pontine regions from the film autoradiographic images. The level of CRH-IR was increased by 30% in the locus coeruleus, 39% in the median raphe and 45% in the caudal dorsal raphe in the depressed suicide subjects compared to controls. No difference in CRH-IR was found in the dorsal tegmentum or medial parabrachial nucleus between the subject groups. These findings reveal that CRH-IR levels are specifically increased in norepinephrine- and serotonin-containing pontine nuclei of depressed suicide men, and thus they are consistent with the hypothesis that CRH neurotransmission is elevated in extra-hypothalamic brain regions of depressed subjects.
 ...
PMID:Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. 1266 Aug 5


1 2 3 Next >>