Unidirectional Specific and Modulated Brain to Blood Transport of Corticotropin-Releasing Hormone

Martins, João Martin; Kastin, Abba J.; Banks, William A.

doi:10.1159/000126974

Cited by 102 publications

(64 citation statements)

References 32 publications

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“…Other studies of CRF infusion in young men have found either a decrease in delta sleep (Holsboer et al, 1988) or no effect on sleep (Born et al, 1989). Exogenous CRF does not cross the blood-brain barrier (Martins et al, 1996) but can Delta sleep response to metyrapone in PSTD TC Neylan et al affect periventricular structures, particularly the hypothalamus. Peripheral administration of CRH antagonists that do not cross the blood-brain barrier have been found to reduce spontaneous waking (Chang and Opp, 1999).…”

Section: Discussionmentioning

confidence: 98%

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combatrelated PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.

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Section: Discussionmentioning

confidence: 98%

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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“…It is also possible that the release of CRF stems from sources other than placenta. Studies in adult mice report the existence of specific unidirectional brain-to-blood transport system for CRF (34). Furthermore, this transport system is acutely modulated by adrenal steroids suggesting the participation in the control of stress response (35).…”

Section: Discussionmentioning

confidence: 99%

Elevated Plasma Corticotrophin Release Factor Levels and In Utero Meconium Passage

et al. 2007

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Intrauterine meconium (MEC) passage and aspiration may result in significant newborn morbidity, though there is little understanding of the physiologic mechanisms for MEC passage. We hypothesized that stress induces fetal MEC passage via corticotrophin releasing factor (CRF), a known mediator of colonic motility in adult rats. Pregnant rats at e22 were subjected to acute hypoxia or normoxia for 35 min, after which rats were anesthetized and fetuses operatively delivered. Amniotic fluid bilirubin and intestinal alkaline phosphatase were measured as markers for MEC passage, and fetal and maternal plasma CRF and corticosterone levels determined. Hypoxic stress induced defecation in all dams and provoked visible MEC passage in all fetuses. Amniotic fluid bilirubin content was significantly higher in hypoxic fetuses versus controls (1.064 Ϯ 0.101 versus 0.103 Ϯ 0.003 O.D. at 410 nm) and intestinal alkaline phosphatase was consistently elevated in MEC stained amniotic fluid. Hypoxia significantly increased plasma CRF (maternal, 82 Ϯ 5 to 196 Ϯ 14 pg/mL; fetal, 284 Ϯ 15 to 1523 Ϯ 185 pg/mL) and corticosterone (maternal, 417 Ϯ 50 to 1150 Ϯ 50 ng/mL; fetal, 96 Ϯ 5 to 182 Ϯ 10 ng/mL) compared with controls. In view of the known action of CRF in adult colonic motility, these results suggest that hypoxic stress-mediated MEC passage in term fetal rats is mediated by a CRF dependent pathway. (Pediatr Res 61: 176-179, 2007)

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“…This effect is likely at the level of the pituitary outside of the blood-brain barrier, as peripherally administered hCRF has poor central penetrance (Martins et al, 1996). Whether this effect is also because of hCRF action in the hypothalamus is unknown.…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-Releasing Factor Testing Reveals a Dose-Dependent Difference in Methadone Maintained Vs Control Subjects

Schluger

Bart

Green

et al. 2003

Neuropsychopharmacol

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Opiate addiction is associated with abnormal function of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis. In general, addiction and withdrawal are associated with abnormal HPA responsivity as demonstrated by baseline, dexamethasone, and metyrapone testing. Following stabilization in methadone maintenance treatment, normalization of HPA axis responsivity is observed. To further investigate HPA axis function associated with heroin addiction and its treatment, saline placebo and human corticotropin-releasing factor (hCRF) were administered intravenously in two doses, one dose lower (0.5 mg/kg) and one dose higher (2.0 mg/kg) than the dose used in standard clinical diagnostics (100 mg), to 16 normal male volunteer controls (NV) and eight male stable-dose methadone-maintained former heroin addicts without ongoing drug or alcohol abuse or dependence (MM). Plasma adrenocorticotrophic hormone (ACTH) and cortisol levels were determined at serial time points. There was no difference in hormonal measurements between the two groups following placebo. NV as well as MM displayed a dose-response effect in plasma ACTH and cortisol levels. MM displayed a significantly greater increase in plasma ACTH levels than the NV following high-dose but not low-dose hCRF (po0.05). There was no significant difference in plasma cortisol levels between the two groups following high-dose hCRF. Thus, despite earlier documented normalization of behavioral function and of several measures of neuroendocrine function during long-term methadone maintenance, some abnormalities in HPA axis responsivity that may be a consequence of heroin exposure, or that may have existed prior to the addiction, can persist during stable methadone treatment.

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Unidirectional Specific and Modulated Brain to Blood Transport of Corticotropin-Releasing Hormone

Cited by 102 publications

References 32 publications

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Elevated Plasma Corticotrophin Release Factor Levels and In Utero Meconium Passage

Corticotropin-Releasing Factor Testing Reveals a Dose-Dependent Difference in Methadone Maintained Vs Control Subjects

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