Non‐Adrenocorticotropin Mediated Effects of Endogenous Corticotropin‐Releasing Factor on the Adrenocortical Activity in the Rat
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Abstract:
Diurnal changes in plasma corticosterone concentrations of rats are supposed to be controlled by low amplitude changes in plasma adrenocorticotropin (ACTH) that run in phase with marked changes in adrenal sensitivity to ACTH (1, 2). These sensitivity changes are probably under neuronal control (3), but the mechanisms remain to be elucidated. By the use of a highly specific monoclonal antibody to rat corticotropin‐releasing factor (CRF) (4), we studied the role of endogenous CR‐ in these processes. Blockade of endogenous CRF prevented the evening rise in plasma ACTH and reduced corticosterone levels to less than 10%. The CRF antibody did not affect morning ACTH concentrations but nevertheless reduced morning corticosterone levels by 40% to 60%. In dexamethasone‐treated rats, immunoneutralization of endogenous CRF caused a similar reduction in the plasma corticosterone response to exogenous ACTH. We conclude that endogenous CRF plays a physiological role in controlling the adrenal sensitivity to ACTH.Keywords:
Corticosterone
Corticotropin-releasing hormone
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The data on the status of the hypothalamic-pituitary-adrenal (HPA) axis in haemodialysis (HD) patients are conflicting. Moreover, a state reminiscent of Cushing's syndrome has been reported in this group of patients. Corticotropin-releasing hormone (CRH), that is produced by the hypothalamus and modulates the secretion of adrenocorticotropic hormone (ACTH), has been shown to be useful as a provocative test of the HPA axis. We investigated the effect of exogenous ovine CRH (oCRH) on plasma levels of ACTH and cortisol in 13 chronic HD patients. The plasma concentrations of immunoreactive CRH following oCRH administration were similar in patients and controls. In all patients, oCRH given intravenously as bolus injection caused a further increase in the already elevated levels of cortisol. The mean basal plasma levels of ACTH were within the normal range. There was, however, a blunted ACTH response to oCRH. We conclude that the HPA axis in chronic HD patients retains the ability to respond to exogenous oCRH. The patterns of the ACTH and cortisol response to this peptide resemble those observed in chronic stress (depression, anorexia nervosa). Besides, the kinetics of disappearance of oCRH indicate that the kidney may not be the major organ that metabolizes oCRH.
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A procedure has been developed for determining the amount of corticosterone in mouse and rat brains. Recovery of corticosterone was shown to be between 80 and 90%. Using this procedure, values for basal levels of brain corticosterone have been obtained. Brain corticosterone levels following ether stress were also determined and were shown to change as rapidly as plasma levels. Corticosterone levels in several brain regions as well as its distribution in subcellular fractions have been determined. Chronic injection of ACTH into BALB/cJ female mice elevated brain corticosterone at a time when the plasma levels were not significantly different from those of the saline-injected controls. It is thought that the direct determination of brain corticosterone offers an approach which is potentially enlightening in the study of the interrelationship between plasma glucocorticoids and ACTH secretion. (Endocrinology90: 1091, 1972)
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Purpose: Evening-dosed HLD200 is a delayed-release and extended-release methylphenidate (DR/ER-MPH) which uses the DELEXIS® drug delivery technology to delay initial drug release by 8–10 hours, providing onset of treatment effect upon awakening and lasting into the evening. Herein, we report clinician-rated assessments of functional impairment based on parent interview during the early morning and late afternoon/evening in children with attention-deficit/hyperactivity disorder (ADHD) from two pivotal, multicenter, phase 3 trials of DR/ER-MPH. Methods: HLD200-107 (NCT02493777) was a placebo-controlled laboratory classroom trial in children (6–12 years) with ADHD. DR/ER-MPH was titrated to …
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Radiation oncology centres are always seeking new ways in which to improve the standard of patient care. In early 2001, a patient information evening was trialled once a month for eight months, with thirty six patients, their family and friends attending. For the last five months, a survey was conducted to determine if the format of these evenings was appropriate or if modifications were needed to further enhance the evenings. The results of the survey indicated that all aspects of the evening were successful and that there was no need to change the current format. The survey also highlighted the positive benefits that the evening had provided for the patients. (author abstract)
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Corticosterone increases food intake in adrenalectomized rats and plasma corticosterone is 3-fold elevated in intact rats during an overnight fast, suggesting that the steroid may stimulate food intake in intact rats when food is provided. If so, this would present a challenge to maintenance of energy balance. Both chronic and acute effects of corticosterone were tested on feeding the next day after a 15 hour overnight fast in 5-day adrenalectomized rats. Similarly, RU486 was given acutely to intact rats. As expected, adrenalectomized rats replaced at surgery with corticosterone exhibited corticosterone dose-related increases in food intake and insulin levels during the first 8 hours after the fast. By contrast, treatment during the fast of: 1. intact rats with the glucocorticoid receptor antagonist RU486, 2. adrenalectomized steroid-replaced rats, with injections of corticosterone or 3. adrenalectomized rats with injections of corticosterone without prior steroid replacement, did not significantly affect food intake during the first 3–8 hours after the fast. Food intake did increase during 24 hours when previously untreated adrenalectomized rats were treated with corticosterone during the fast. In response to a stressor, acute corticosterone responses of similar magnitude occurred in intact rats both fed and fasted, but this did not affect their food intake during next 24 hours. We conclude that although chronic corticosterone treatment of adrenalectomized rats increases food intake, there is a prolonged lag between corticosterone treatment and increased food intake. Thus, acute corticosterone responses to stressors do not perturb the regulation of energy balance in intact animals; other mechanisms, such as elevated insulin secretion, intervene to blunt the chronic effects of corticosterone on food intake, and thus energy balance.
Corticosterone
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Corticosterone
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Basal (medicine)
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Corticotropin-releasing hormone
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