Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endogenous opioids and their receptors are known to play a major role in neoplasia. In the present study, naltrexone (NTX), a potent opioid antagonist, was utilized to explore the interactions of opioids and opioid receptors in mice with transplanted neuroblastoma (S20Y). Tumors from mice subjected to either intermittent (4-6h/day; 0.1 mg/kg NTX) or complete (24 h/day; 10 mg/kg NTX) opioid receptor blockade exhibited an up-regulation of DADLE and Met-enkephalin binding sites, as well as tissue levels of beta-endorphin and Met-enkephalin. Binding affinity to [D-Ala2,D-Leu5]enkephalin (DADLE) or ethylketocyclazocine (EKC), the levels of plasma beta-endorphin, and the anatomical location and quantity of Met- and Leu-enkephalin and cytoskeletal components (i.e. tubulin, actin, brain spectrin (240/235) were similar in NTX and control tumor-bearing animals. Tissue viability of the 0.1 NTX group was increased compared to controls. Both mitotic and labeling indexes were increased during the period of opioid receptor blockade, but decreased in the period subsequent to receptor blockade. NTX treatment produced a 2-fold increased in sensitivity to opioids. Met-enkephalin (10 mg/kg) produced a depression in both mitotic and labeling indexes in tumor-bearing mice that could be reversed by naloxone (10 mg/kg) administration. Thus, the endogenous opioids are trophic agents that inhibit growth by suppressing cell proliferation. The duration of receptor blockade by opioid antagonists modulates these actions, affecting both tumor incidence and survival time. Complete opioid receptor block prevents the interaction of increased levels of putative growth-related peptides with a greater number of opioid receptors, thereby increasing cell proliferation and accelerating tumor growth. With intermittent blockade, an enhanced opioid-receptor interaction occurs during the interval when the opioid antagonist is no longer present, producing an exaggerated inhibitory action on cell proliferation and the repression of tumorigenic events.
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PMID:Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. 254 Aug 73

Alterations in peripheral blood leukocyte distribution in major depression, including leukocytosis, neurotrophilia and lymphopenia, have been described. To assess peripheral white blood cells and the hypothalamic-pituitary (HP) axis in drug-free patients with major depression, we measured the total white blood cell count (WBC), and percentage of lymphocytes, and the plasma levels of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH) and prolactin (PRL). Twenty male patients with major depression had relative lymphopenia and leukocytosis when compared with 20 age, sex and racematched control subjects. Elevated Beck and Hamilton depression scores correlated with a decreased percentage of lymphocytes, in a group of all subjects combined. There was a weak tendency for elevated growth hormone to correlate with relative lymphopenia in the control subjects only. Relative lymphopenia and leukocytosis may be a part of the psychobiology of major depression.
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PMID:Peripheral white blood cells and HPA axis neurohormones in major depression. 254 Oct 94

A substantial body of data suggests that excessive cortisol secretion in depression may result from dysregulation at several sites within the hypothalamic-pituitary-adrenocortical (HPA) axis. The alterations in regulatory mechanisms are thought to result from a limbic system-hypothalamic "overdrive" of corticotropin-releasing hormone (CRH). We also have demonstrated that excessive secretion of cortisol may result from an abnormal adrenocortical responsiveness to adrenocorticotropic hormone (ACTH), and we have postulated that corticotropic cells within the pituitary mediate between excessive secretion of CRH from the hypothalamus and hypercortisolemia secondary to adrenocortical hyperplasia and enhanced sensitivity to ACTH at the adrenal cortex. The present report describes a series of clinical experiments utilizing several neuroendocrine probes, as well as computer-assisted tomography, to examine the complexities of the HPA axis dysregulation in depression. These studies support the hypothesis that a limbic system-hypothalamic disturbance results in excessive CRH secretion as well as enhanced adrenocortical activity, and that these factors contribute to excessive cortisol secretion in patients with depression. These data further support the hypothesis that endogenous affective disorders are best characterized in the framework of a generalized biological disturbance of HPA axis function which involves both central and peripheral endocrine sites.
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PMID:The assessment of abnormalities in hormonal responsiveness at multiple levels of the hypothalamic-pituitary-adrenocortical axis in depressive illness. 254 2

To investigate the relationships between dexamethasone (DEX) and post-DEX cortisol and adrenocorticotropic hormone (ACTH) levels, the authors measured DEX at 8.00 a.m. and post-DEX cortisol and ACTH levels at 8.00 a.m. and 4.00 p.m. in 72 depressed patients categorized according to DSM-III. Cortisol non-suppressors exhibited significantly (P = 0.0006) decreased levels of DEX compared to suppressors. DEX levels at 8.00 a.m. explained 21.1% of the variance in the post-DEX cortisol values at 8.00 a.m. and 34.5% of those at 4.00 p.m. DEX levels were not significantly different among minor depressives (300.40, 309.00), major depressives without melancholia (296.X2) or with melancholia and/or psychotic features (296.X3, 296.X4). In the latter the post-DEX cortisol was significantly increased compared to all other depressives and these differences remained significant even after adjusting for the variations in DEX (by means of regression analysis). Also the diagnostic performance of the post-DEX cortisol values for major depression with associated features versus minor depression was not substantially affected when the DEX levels were accounted for. ACTH levels after DEX were shown to correlate significantly (P less than 0.05) and negatively with DEX. Although post-DEX ACTH levels did not differ among the DSM-III diagnostic categories, cortisol non-suppressors averaged significantly (P = 0.0004) higher ACTH levels than suppressors.
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PMID:The influences of dexamethasone levels on the predictive value of the DST for unipolar major depression and the relationships between post-dexamethasone cortisol and ACTH levels. 254 36

The effects of 2-day and 7-day cortisol treatment on immunoreactive corticotropin (ACTH) and beta-endorphin concentrations were measured in the cerebral cortex, hippocampus, hypothalamus, and cerebellum in male rats. Plasma ACTH, beta-endorphin, corticosterone, and cortisol levels were also measured in parallel. Cortisol administration by osmotic minipumps (25 mg/kg/day) maintained a constant, moderately high concentration (23.0 +/- 2.7 micrograms/100 ml) of this glucocorticoid in plasma. Two-day cortisol treatment suppressed the plasma concentration of ACTH and corticosterone, and also decreased, to a lesser degree, concentrations of beta-endorphin. ACTH and beta-endorphin levels in the brain remained unchanged after 2 days of cortisol treatment. After 7-day treatment, however, plasma concentrations of ACTH and beta-endorphin further decreased, while ACTH and beta-endorphin concentrations in the cortex and beta-endorphin concentrations in the cerebellum were also significantly decreased. Peptide concentrations in other brain areas did not change significantly with either 2-day or 7-day cortisol treatment. These data suggest that there are delayed effects of glucocorticoids on pro-opiomelanocortin peptide secretion and/or metabolism in the central nervous system. These findings are consistent with the impaired cognitive functions of patients with diseases, such as Cushing's syndrome and depression, that have long-lasting elevated cortisol secretion.
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PMID:Delayed effects of chronic cortisol treatment on brain and plasma concentrations of corticotropin (ACTH) and beta-endorphin. 254 10

A yin-yang hypothesis is presented linking noradrenergic activity, thromboxane, melatonin, left hemisphere functioning, and cyclic AMP on the one hand, and dopamine, beta-endorphin, calcium, right hemisphere functioning, and cyclic GMP on the other. It is further suggested that there is a yoking of NA, TXA2, serotonin and melatonin in the left hemisphere, and a similar yoking of DA, BE, calcium and cGMP in the right. Evidence is presented to support the hypothesis that each element (NA, TXA2, etc.) on one side can modulate or balance a corresponding element (DA, BE, etc.) on the other. It is suggested that thromboxane is the key element in noradrenergic overactivity and that not taking this into consideration has confounded much prior research. This theory takes into account information processing models as well as pharmacological data and neurochemical theory on coupling of adenylate cyclase to its hormone receptors. Inhibiting noradrenergic overactivity can be obtained by inhibiting thromboxane and concomitantly activating opiate receptors. This protocol may have clinical utility in treating a wide range of disorders such as: anxiety, depression, schizophrenia, sleeplessness, withdrawal states, enuresis, Gilles de la Tourette syndrome, Parkinsonism, Alzheimers, dementia, anorexia, infant ruminations, essential tremor, spasticity of spinal cord injury, diarrhoea, ulcerative colitis, extrapyramidal symptoms, akathisia, neuroleptic malignant syndrome, attention deficit disorder, hyperhidrosis, and possibly AIDS.
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PMID:Inhibiting noradrenergic overactivity by inhibition of thromboxane and concomitant activation of opiate receptors via dietary means. 254 22

Since the discovery of CRH in 1981, several investigators have reported abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in response to direct stimulation of the corticotroph cells in patients with psychiatric disorders. To further explore HPA system integrity in major depressive disorders, 13 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 100 micrograms synthetic human CRH as an iv bolus dose. Compared to that in the normal subjects, in the depressed patients a significant attenuation of the net ACTH release after CRH administration (772 +/- 597 vs. 263 +/- 286 pmol/min.L; P less than 0.02) was observed, while beta-endorphin and cortisol responses did not differ significantly between the groups. The magnitudes of ACTH and cortisol release were negatively correlated in the patient group only (r = -0.67; P less than 0.01). Thus, the blunted ACTH response to CRH in depression might be related to hypercortisolemia, while the implications of the apparent dissociation of ACTH and beta-endorphin after CRH administration still remain unclear. Our data support the hypothesis that the hyperactivity of the HPA system in depression most likely is a consequence of CRH hypersecretion, the origin of which may be explained by abnormal central glucocorticoid receptor or neurotransmitter regulation.
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PMID:Blunted adrenocorticotropin but normal beta-endorphin release after human corticotropin-releasing hormone administration in depression. 254 28

A wide range of abnormalities of the hypothalamo-pituitary-adrenal (HPA) axis has been described in depression. This paper reviews recent advances in the understanding of this system, and draws them together to construct a model for the purposes of further research and discussion. It is proposed that there are two fundamental changes which both originate in the hypothalamus: an increased secretion of corticotropin-releasing hormone, and a neurally mediated adrenal hyper-responsivity to ACTH. The resulting changes in hormone regulation would be expected to produce all the characteristic HPA axis abnormalities commonly seen in depression. The model makes several predictions which could be tested by future experiment.
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PMID:Hypothalamo-pituitary-adrenal axis abnormalities in depression: a review and a model. 254 24

(1) The availability of short amino acid sequences of the naturally occurring ACTH 1-39 molecule has made it possible to separate the corticotropic characteristics of the parent molecule from its neurotrophic effects. Potent neurotrophic fragments are ACTH 4-10, an analog of ACTH 4-9 (Org 2766), and alpha-MSH (ACTH 1-13), peptide fragments that do not evoke corticosteroid secretion, yet clearly affect both the development and regeneration of peripheral nerve. (2) Early postnatal administration of either ACTH 4-10 or Org 2766 accelerates the neuromuscular development of the immature rat, increasing the contractile strength of the EDL muscle and inducing more rapid muscle contractions. Grasping strength and motor activity are increased; these are all changes indicative of more rapid neuromuscular maturation. Prenatal peptide treatment elicits a more complex pattern of response since administration early in gestation (GD 3-12) accelerates neuromuscular development whereas later administration (GD 13-21) decelerates maturation. (3) ACTH peptides have a similar accelerating effect on the morphology of the developing neuromuscular junction. At two weeks of age, nerve arborization is conspicuously increased by postnatal administration of either ACTH 4-10 or Org 2766, as is nerve terminal branching within the endplate itself. However, this is preceded by an initial depression of nerve branching in the 7-day-old rat pup. We conclude that while the developing neuromuscular system is sensitive to ACTH peptides, this susceptibility is age-related. The crucial role of these peptides may be limited to very brief, defined periods during which the peptides may interact with trophic or growth-associated substances, each of which may have its own decisive, circumscribed time frame of influence. (4) Perinatal administration of ACTH peptides affects CNS development. One measurable indication of this is an acceleration of eye opening. Early exposure to ACTH peptides has long-lasting effects on behavior, apparent when these animals are tested as adults. Increased spontaneous motor activity, heightened states of arousal and agitation, and changes in social behavior have been reported. Certain avoidance responses and tests of visual discrimination in male rats are improved by neonatal treatment with alpha-MSH. Overall motor activity is increased and the normal period of hyperactivity is initiated earlier. Male sexual behavior is decreased and sexually dimorphic behaviors in males are eliminated. alpha-MSH may alter the development of its own dopaminergic feedback circuitry while ACTH affects serotonin levels in the preoptic nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:ACTH modulation of nerve development and regeneration. 254 30

To explore and to compare hypothalamic-pituitary-somatotropic (HPS), hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenocortical (HPA) axis function in depression, 30 subjects (15 patients with a major depressive episode and individually matched controls) received 50 micrograms growth hormone-releasing hormone-44 amide at 9:00, 200 micrograms thyrotropin-releasing hormone (TRH) at 9:00 and 100 micrograms human corticotropin-releasing hormone (CRH) at 18:00 on consecutive days as an i.v. bolus dose. Compared with controls, depressed patients showed blunted growth hormone (GH) responses to GHRH, decreased TRH-induced thyrotropin (TSH) release and reduced corticotropin (ACTH) but normal cortisol secretion following CRH. ACTH secretion following CRH and TRH-induced TSH release were positively correlated across depressed patients and controls but no significant correlations between GH responses to GHRH and TRH-induced TSH release or ACTH and cortisol secretion following CRH administration were demonstrated. Our findings suggest that altered HPT and HPA axis function associated with depression are triggered by factors that are at least partly different from those that cause HPS system dysfunction. We conclude that the pathophysiological process resulting in aberrant neuroendocrine secretory dynamics associated with depression may primarily occur at a suprapituitary site, and that HPS, HPT and HPA axis dysfunction may be precipitated by complex central and peripheral regulatory mechanisms involving largely independent factors.
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PMID:Endocrine responses to growth hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone in depression. 254 70


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