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)

Experiments were conducted on male albino rats (298); a study was made of the effect of experimental thyrotoxicosis of various severity on the state of the hypothalamo-hypophyseal-adrenal system. It was found that the hypothalamo-hypophyseal-adrenal system responded differently to the excess of thyroid hormone, depending on the strength and duration of action. Mild thyrotoxicosis was accompanied by its activation expressed in increased CRF of the hypothalamic extracts, a reduction of the ACTH in the hypophysis and a fall of ascorbic acid content in the adrenal glands. Severe and prolonged thyrotoxicosis was accompanied by a depression of the hypothalamo-hypophysio-adrenal system function. It was concluded that the action of thyroid hormones on the CRF secretion served as the leading mechanism of the mentioned reactions.
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PMID:[The effect of experimental thyrotoxicosis on the state of the hypothalamo-hypophyseo-adrenal system in rats]. 17 50

A 41-year-old man with hypothalamic hypopituitarism (CRF-ACTH type) that persisted for 2 years after discontinuation of exogenous dexamethasone was treated with bilateral ECT for severe chronic depression. The depression improved only evanescently after 17 ECT sessions but the hypothalamic-pituitary suppression cleared completely and permanently, based on responses to four metyrapone stress tests in a 2-year follow-up period. ECT may be an effective treatment for persistent hypothalamic-pituitary suppression, even in the absence of a psychiatric disorder.
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PMID:Electroconvulsive therapy for iatrogenic hypothalamic-hypopituitarism (CRF-ACTH type). 22 58

CRF is released in response to various stressors and regulates ACTH secretion and glucocorticoid production. CRF overproduction has been implicated in affective disorders, such as depression and anorexia nervosa, and may lead to Cushing's syndrome. To test whether CRF overproduction leads to Cushing's syndrome and to develop an animal model of chronic pituitary-adrenal activation, the CRF gene was expressed under control of the metallothionein promoter in transgenic mice. CRF transgenic animals exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. These animals display physical changes similar to those of patients with Cushing's syndrome, such as excess fat accumulation, muscle atrophy, thin skin, and alopecia. These findings indicate that chronic production of excess CRF results in sustained stimulation of pituitary corticotrope cells, resulting in elevated ACTH and consequent glucocorticoid overproduction, a condition that leads to the development of Cushing's syndrome. Analysis of CRF mRNA distribution revealed that transgene expression is primarily restricted to cells that express the endogenous CRF gene and does not follow the pattern predicted of a metallothionein-regulated gene. These results suggest that DNA elements located outside of the CRF promoter but present within the CRF intron, coding, or 3'-flanking regions may contribute to the cell type specificity of CRF gene expression.
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PMID:Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. 159 49

The effects of chronic (14 day) intracerebroventricular infusion of various amounts of ovine corticotropin-releasing factor (oCRF) on the circadian blood corticosterone rhythm in male rats were examined. Control (saline-infused) rats showed distinct blood corticosterone rhythms over 48 h with nadirs at 0900 h and peaks at 2100 h on days 6-7 and 13-14. oCRF at 3 pmol/h did not affect the circadian corticosterone rhythm on these days. When oCRF was infused at a rate of 12 pmol/h, blood corticosterone was increased throughout the 48 h periods. A significant circadian rhythm remained at days 6-7, but continuous infusion for an additional 7 days disrupted the rhythm. Higher doses of oCRF (48 and 240 pmol/h) obliterated the rhythm during both periods; the disruption was characterized by an increase in corticosterone during the lights-on period without a substantial change in the evening maximum. Thus, the blood corticosterone concentration was eventually confined within a narrow range, not exceeding the normal circadian peak, over a wide dose range of centrally administered CRF. Significant effects of oCRF on body and adrenal weight were observed only at the two highest doses used. These findings may provide some insight into the state of the hypothalamic-pituitary-adrenal axis in animals exposed to chronic stress and in patients with depression.
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PMID:Effect of chronic intracerebroventricular infusion of corticotropin-releasing factor on circadian corticosterone rhythm in the rat. 238 47

A subchronic toxicity study of calcium lactate was carried out in male and female F344 rats to estimate the maximum tolerated dose for a subsequent long-term toxicity/carcinogenicity study. Experiment I: Rats were divided into 6 groups, each consisting of 5 males and 5 females. Calcium lactate was dissolved in water at concentrations of 5, 2.5, 1.25, 0.6, 0.3 and 0%, each animal group was given one of these solutions as the drinking water for 13 wk. In all groups, basic diet (CRF-1) was given ad libitum. No fatalities occurred. In all treated groups, including the 5% group, a less than 10% depression of body-weight gain as compared with the control group was observed. Some parameters in the hematological and biochemical data demonstrated change in the treated groups. On histological examination, however, no severe toxicological findings were found in any of the treated groups. Experiment II: Rats were fed synthetic diet B, containing 30, 20, 10, 5 or 0% calcium lactate. In the highest dose group, body weight-gain was strongly reduced as compared with the control group. Histological examination revealed nephrocalcinosis in all groups, including the control group, and adverse dose-effect relation was observed with regard to degree of its development. Females exhibited this lesion to a greater extent than males. Experiment III: Rats were given CRF-1 or synthetic diet B for 8 wk. Nephrocalcinosis was found only in the group given synthetic diet. It was ascertained that the nephrocalcinosis observed in Exp. II and III was dependent on the low Ca/P ratio (Ca/P: less than 1) of the synthetic diet B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Subchronic oral toxicity study of calcium lactate in F344 rats]. 263 38

Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis of some seizure states. Techniques for amplification of mRNA expression have identified specific neuronal proteins and peptides. Knowledge of protein and propeptide structural cleavage sites has suggested previously unknown candidates for modular systems in epileptic states. Technological advances in automated peptide sequencing and synthesis have allowed the development of metabolically resistant analogs and antagonist peptides. The anticonvulsant potencies of CCK, TRH, and opioid peptides have been defined more clearly with these methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. 287 23

Synthetic ovine corticotropin releasing factor (o-CRF) was administered as an intravenous bolus (100 micrograms) to eight patients suffering from a major depressive disorder, endogenous subtype. All patients showed inadequately suppressed cortisol levels after 1 mg dexamethasone. After clinical remission and normalized dexamethasone responses, these patients were reinvestigated with o-CRF stimulation. The mean adrenocorticotropic hormone (ACTH) release from the pituitary corticotroph cells was indiscriminate at both test sessions. Cortisol and corticosterone output after o-CRF tended to be higher during depression than after recovery. The o-CRF-induced increments observed with corticosterone were more marked in comparison with cortisol. Within the limitations of the current protocol, our preliminary data lend support to the view that an increased pituitary ACTH reserve or adrenocortical steroid reserve is not likely to be responsible for the defective pituitary-adrenal regulation in some dexamethasone-resistant depressives.
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PMID:ACTH, cortisol, and corticosterone output after ovine corticotropin-releasing factor challenge during depression and after recovery. 298 88

The 41-amino acid CRF fulfils all the criteria for a corticotrophin releasing factor, although considerable evidence suggests that other factors, particularly VP, also play a physiologically significant role in controlling ACTH release. Although human CRF has now been identified as a 41-residue peptide, most studies to date have used oCRF-41 in their exploration of the physiology and pathology of the hypothalamic--pituitary--adrenal axis. Low doses of oCRF-41 appear to be safe, and for specific tests of the readily-releasable pool of ACTH and related peptides 100 micrograms is a practical dose for most purposes. Although serious side-effects have only been noted at doses above 100 micrograms, it is reasonable to monitor all patients administered CRF-41 with great care, and in particular to be alert to hypotension, especially in patients with corticosteroid deficiency. There is little doubt that, in combination with the standard insulin-tolerance test, the CRF test is a useful means of diagnosing hypothalamic or portal dysfunction in patients with secondary adrenal failure. However, in the diagnosis and differential diagnosis of Cushing's syndrome, the role of the CRF test remains unclear. In normal subjects, a high basal cortisol level usually inhibits the response to CRF, such that a greatly enhanced response is suggestive of pituitary-dependent Cushing's syndrome. In patients with diagnosed ACTH-dependent Cushing's syndrome, an absent response to CRF predisposes towards an ectopic source of ACTH. However, there are exceptions in all directions, and it is uncertain whether the CRF test will prove of greater value than the traditional procedures, such as the dexamethasone suppression test. The differential diagnosis of depression and Cushing's disease may be its greatest value. In terms of treatment, there are as yet few data on the usefulness of CRF in expediting recovery of the pituitary-adrenal axis following long-term suppression, such as in patients with Cushing's syndrome treated by removal of a unilateral adenoma or trans-sphenoidal microadenomectomy. It is possible that such treatment may eventually be a useful application of CRF, although data are not yet available.
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PMID:The CRFs and their control: chemistry, physiology and clinical implications. 300 78

To further explore hypothalamic pituitary adrenal regulation in patients with affective illness, we administered 1 microgram/kg of synthetic ovine corticotropin releasing factor at 2000h to 26 drug-free patients with this disorder and to 15 healthy controls. Compared to controls, depressed patients (N = 12) showed a significant elevation in baseline cortisol and significant reductions in the net ACTH and cortisol responses to corticotropin releasing factor. These findings were normal in manic (N = 6) and improved (N = 8) subjects. An additional finding was that baseline cortisol and net ACTH and cortisol responses to CRF were negatively correlated in the entire group of patients and controls as well as in the patients alone. These data indicate that the reduced ACTH and cortisol responses to CRF in depression reflect normal functioning of the pituitary corticotroph cell (i.e., that the negative feedback effect of cortisol on ACTH secretion in depression is physiologically intact, effectively serving as a brake on the ACTH response to exogenous CRF. Thus, the hypercortisolism of depression may be due to a hypothalamic defect, possibly involving hypersecretion of endogenous CRF. This possibility may be of particular interest in light of clinical observations that depression can often be precipitated by stress and by data in experimental animals that CRF may influence several processes known to be altered in the overall symptom complex of depression.
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PMID:Abnormal ACTH and cortisol responses to ovine corticotropin releasing factor in patients with primary affective disorder. 301 Mar 82

ACTH-release by primary cultures of rat anterior pituitary cells in response to CRF, vasopressin, epinephrine, norepinephrine and VIP is readily suppressible by dexamethasone. Rat hypothalamic extract-induced ACTH release is less sensitive to the inhibitory effect of dexamethasone than that elicited by CRF and the other secretagogues mentioned above. In studying the additive and potentiating effect on ACTH release of CRF in combination with vasopressin, VIP and the catecholamines it became evident that only the combination of micromolar concentrations of epinephrine or norepinephrine together with nanomolar concentrations of CRF will make ACTH release significantly less sensitive to the suppressive effect of dexamethasone. Other combinations of CRF and vasopressin or CRF and VIP will render ACTH release as suppressible to dexamethasone, as that elicited by each of these compounds by itself. This observation in the rat might explain at least in part the observation that a diminished suppressibility of the pituitary-adrenal axis to dexamethasone can be found in patients with psychiatric disease, especially depression.
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PMID:High concentrations of catecholamines selectively diminish the sensitivity of CRF-stimulated ACTH release by cultured rat pituitary cells to the suppressive effects of dexamethasone. 301 54


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