Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A regimen of twice daily metyrapone injections (100 mg/kg), resulted in pharmacological adrenalectomy of pregnant rats and fetuses in utero, i.e. depression of plasma corticosterone and elevation of plasma adrenocorticotropic hormone (ACTH). Toxicity was minimal on days 14-17 of pregnancy, and increased with higher maternal weight and pregnancy progression. Corticotropin releasing hormone (CRH) messenger RNA abundance in the pregnant adults increased significantly within 48 h of metyrapone initiation. No change in CRH gene expression in the paraventricular nucleus of fetuses (days 17-18) was seen, even after 72 h of the regimen. This is compatible with the independence of CRH gene expression of glucocorticoid feedback in the fetal rat.
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PMID:CRH gene expression in the fetal rat is not increased after pharmacological adrenalectomy. 133 78

Corticotropin releasing factor (CRF) is a newly sequenced peptide first isolated from sheep hypothalami and thought to be an important modulator of both the pituitary-adrenal axis and the sympathetic nervous system. We administered intravenous, intramuscular, and intracerebroventricular CRH to non-human primates and measured plasma ACTH, beta endorphin, cortisol, GH and PRL responses to CRF. In addition, we determined the pharmacokinetic properties of I125 in these primates. We administered CRF as an intravenous bolus or as a continuous infusion to normal volunteers and as an intravenous bolus to patients with disorders of the hypothalamic-pituitary-adrenal axis, such as Cushing's syndrome and adrenal insufficiency, and patients with endogenous depression and mild hypercortisolism, and assessed their plasma ACTH, cortisol, GH and PRL responses. In addition, we determined the pharmacokinetic properties of CRF in man by measuring CRF immunoreactivity in plasma. CRF given intravenously to primates or man is a slowly metabolized, long-acting, secretagogue of ACTH, beta-endorphin and cortisol. When given intracerebroventricularly to primates it stimulates the hypothalamic-pituitary-adrenal axis without escaping into the plasma and it is actively cleared in the CNS. It does not cross the blood brain barrier appreciably when given intravenously. CRF given to primates and men as an intravenous continuous infusion has only mild ACTH stimulating effects and this may be due to an intact cortisol negative feedback system. Finally, CRF causes characteristic plasma hormone responses in patients with Cushing's disease, adrenal insufficiency and depression.
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PMID:Corticotropin releasing factor: basic studies and clinical applications. 299 71

Twenty-two subjects (11 patients with major endogenous depression and 11 controls) received an intravenous test dose of 100 micrograms human corticotropin-releasing hormone (h-CRH). Corticotropin (ACTH), but not cortisol, responses were blunted in depressives. Basal cortisol secretion was higher in depressives than in controls and was negatively correlated to the corticotropin response following h-CRH. This finding indicates the integrity of the glucocorticoid-dependent negative feedback regulation in depression and supports the view that hypercortisolism in depression is primarily due to a suprapituitary disturbance. Comparison of ACTH responses after h-CRH with thyrotropin (TSH) output following thyrotropin-releasing hormone (TRH) revealed a positive correlation (r = 0.65, p less than 0.001). The concordance between ACTH and TSH responses after specific challenges suggests that regulation of both systems is at least in part under a common control.
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PMID:Human corticotropin-releasing hormone in depression--correlation with thyrotropin secretion following thyrotropin-releasing hormone. 301 Nov 29

Corticotropin releasing factor (CRF) is a 41 amino acid peptide first isolated from sheep hypothalami and thought to be a principal modulator of the hypothalamic-pituitary-adrenal cortical (HPA) axis. We report herein a series of clinical studies with CRF in healthy volunteers and in patients with abnormalities in HPA function, including depression, Cushing's disease, Cushing's syndrome, and Addison's disease. Our data indicate that CRF can be a diagnostic aid in distinguishing various disorders of the HPA axis from one another, including Cushing's disease from depression and secondary from tertiary adrenal insufficiency. Moreover, the hormone responses to CRF help clarify the pathophysiology of the HPA abnormalities in several disorders. For instance, our data indicate that hypercortisolism in Cushing's disease results principally from a defect at the level of the pituitary; in contrast, in depression the defect seems to be hypothalamic, possibly involving hypersecretion of endogenous CRF. This latter possibility is of particular interest in light of clinical observations that depression often can be precipitated by stress. Moreover, data from experimental animals show that CRF may influence several processes known to be altered in the overall symptom complex of depression, including not only pituitary-adrenal function, but also motor activity, appetite regulation and sexual behavior.
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PMID:Clinical studies with corticotropin releasing factor: implications for the diagnosis and pathophysiology of depression, Cushing's disease, and adrenal insufficiency. 387 72

In addition to a genetic contribution to the vulnerability for mood and anxiety disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), a preeminent role of early adverse life events in the pathogenesis of these disorders has been postulated. Corticotropin releasing factor (CRF), which has been conclusively documented to be the major regulator of the mammalian stress response, may be the seminal neurobiological substrate mediating the effects of early life stress on subsequent psychopathology. Central administration of CRF produces many of the physiological and behavioral effects of stress and of anxiety and depression. Clinical studies have provided evidence for increased activation of CRF neuronal systems in both MDD and PTSD. Similar hyperactivity of CRF neurons and sensitization of the pituitary-adrenal stress response has been observed in adult animals exposed to stress early in life. We propose that early adverse life events might render the human individual vulnerable to the effects of stress later in life, resulting in an increased risk for developing psychopathology via long-lived alterations in CRF-containing neural circuits. Based on these findings, new therapies including early intervention can now be developed to treat individuals exposed to severe stress early in life.
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PMID:Persistent changes in corticotropin-releasing factor systems due to early life stress: relationship to the pathophysiology of major depression and post-traumatic stress disorder. 923 Jun 30

Neuroendocrine activation during stress is affected by many factors contributing to the variability of the stress response. The present study was aimed at evaluating long-term changes in hypothalamo-pituitary-adrenocortical (HPA) axis function and in hedonic behavior in adult offspring prenatally stressed by maternal food restriction, with attention on possible gender differences. Adult offspring were blood sampled via a tail artery cannula. Prenatally stressed females had significantly higher adrenal weights compared to males. Plasma ACTH levels, which rose in response to acute stress induced by handling, were significantly higher in females compared to those in males. A similar pattern was found in plasma corticosterone. The rise in ACTH levels was more pronounced in prenatally stressed rats though the rise in corticosterone failed to be modified. Corticotropin releasing hormone (CRH) and proopiomelanocortin mRNA levels in the hypothalamic paraventricular nucleus and anterior pituitary, respectively, were found to be unchanged. The present experiments failed to reveal a decrease in hedonic behavior in prenatally stressed rats. In contrast, in male offspring a tendency to a higher sucrose preference was observed. These data together with observed changes in hormone and CRH mRNA levels indicate that the gestational stress used did not result in a depression-like state in adult offspring.
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PMID:Hypothalamo-pituitary-adrenocortical axis function and hedonic behavior in adult male and female rats prenatally stressed by maternal food restriction. 1218 80

Corticotropin releasing factor (CRF), localized in extrinsic afferents in the mammalian cerebellum, is defined as a neuromodulator within cerebellar circuits, and appears to be an essential element in the generation of long term depression, a proposed mechanism for motor learning. These physiological studies are based on exogenous application of CRF and do not address potential mechanisms that may influence endogenous release of the peptide. In the present study, immunohistochemistry was used to analyze changes in the lobular distribution of CRF-like immunoreactivity (LIR). In addition radioimmunoassay (RIA) was used to quantify changes in levels of the peptide in the cerebellum following stimulation of the inferior cerebellar peduncle (ICP) at 10 or 40 Hz or the inferior olivary nucleus (ION) at 1, 5, 10, or 20 Hz. Results indicate that there is a greater distribution of CRF-like-immunolabeled climbing fibers, mossy fibers, and astrocytes in all lobules of the cerebellum that is directly related to stimulation frequency. Maximal effects were elicited with 40 Hz ICP and 5-10 Hz ION stimulation. Quantitatively, the RIA studies indicate that there is a significant increase in CRF levels in the vermis, hemispheres and flocculus that correlates closely with stimulation frequency. In conclusion, stimulation of cerebellar afferents induces a significant change in the distribution and levels of CRF-LIR in climbing fibers, mossy fibers and glial cells. This suggests that the modulatory effects ascribed to CRF may influence a greater number of target neurons when levels of activity in afferent systems is increased.
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PMID:Frequency-dependent expression of corticotropin releasing factor in the rat's cerebellum. 1452 95

Clinical and experimental studies on animals indicate that depression is associated with increased plasma cytokine acute phase protein concentrations and hypothalamic-pituitary-adrenal axis (HPA) activation. Additionally it has been detected that immunological activation induces stress-like behavioural and neurochemical changes in organisms of animals and humans. Hypersecretion of cytokines in response to stress or to endogenous trigger factors may induce depressive symptoms. Corticotropin releasing hormone (CRH) overproduction in the brain also may participate in cytokine-induced behavioural and neurochemical changes. Treatment with antidepressants conferred protection against cytokine-induced depressive-like biological and behavioural changes. This is mainly due to alterations of the pro-/anti-inflammatory cytokine balance. There is a substantial body of evidence that the immune system plays a major role in aetiology of depression and that cytokines participate in neurochemical, behavioural and endocrine changes in this illness.
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PMID:[The role of cytokines in depression]. 1463 99

The identification of the various elements of the Corticotropin Releasing Factor (CRF) system including the characterisation of four mammalian CRF-related peptides, the cloning of two CRF receptor subtypes 1 and 2 (CRF1; CRF2) and the development of selective CRF1 receptor antagonists has allowed investigators to establish an important role for the CRF signalling pathways in coordinating the physiological and behavioural components of the stress response. In particular, compelling preclinical evidence showed that both central and peripheral injection of CRF mimicked stress-induced stimulation of colonic motility, transit, defaecation, and occurrence of diarrhoea along with degranulation of mast cells, and increased secretion of prostaglandin E2, mucus, and ionic permeability. Central CRF also increased abdominal pain from colorectal distention in rats and peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. Non-selective CRF antagonists for receptors 1 and 2 and selective CRF, antagonists inhibit exogenous (central or peripheral) CRF, and acute stress-induced stimulation of colonic motor and secretory function and visceral hyperalgesia. CRF1 receptors mediate stress-related anxiogenic and depression-like behaviours in rodents and CRF, antagonist reduced depression in a phase II clinical trial. These findings lend support to the hypothesis that hyperactivation of CRF1 receptors may contribute to the co-morbidity of anxiety and depression and irritable bowel syndrome. Targeting these pathways with selective CRF1 antagonists may be a novel therapeutic venue for diarrhoea-predominant IBS patients.
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PMID:Role of corticotropin releasing factor receptor subtype 1 in stress-related functional colonic alterations: implications in irritable bowel syndrome. 1614 97

The purpose of this preliminary study was to evaluate the relationship between a possible biochemical marker of stress, 24-h urinary concentrations of Corticotropin Releasing Factor-Like Immunoreactivity (CRF-LI), and ratings of stress-related symptoms like depression and anxiety, as well as to evaluate pain and emotional reactions in patients with fibromyalgia (FM). Another purpose was to study the effects of massage and guided relaxation, with respect to change in the same variables. Urine sampling and ratings were performed before treatments, after and 1 month after completed treatments. Concentrations of CRF-LI was analysed with radioimmnoassay technique. For the assessment of depression, anxiety and pain the CPRS-A questionnaire was used and for rated pain and emotional reactions the NHP questionnaire was used. The 24-h urinary concentration of the CRF-LI was found to be related to depression, mood and inability to take initiative. After treatment the urinary CRF-LI concentrations and the rated levels of pain and emotional reactions were found to have decreased. In conclusion, the 24-h urinary CRF-LI concentration may be used as a biochemical marker of stress-related symptoms such as depression in patients with FM and possibly also other conditions characterized by chronic pain. Therapies such as massage and guided relaxation may be tried for the amelioration of pain and stress but further studies are required.
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PMID:Corticotropin releasing factor in urine--a possible biochemical marker of fibromyalgia. Responses to massage and guided relaxation. 1671 15


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