Basal secretory activity of the hypothalamo–pituitary–adrenocortical axis is enhanced in healthy elderly. An assessment during undisturbed night-time sleep

Dodt, Christoph; Theine, Karl-Josef; Uthgenannt, Dirk; Born, Jan; Fehm, Horst L.

doi:10.1530/eje.0.1310443

Cited by 72 publications

(40 citation statements)

References 30 publications

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“…The present outcomes must be distinguished conceptually from measurements of individual ACTH or cortisol concentrations or production rates, which have disclosed both age (3,4,17,38,39,51) and gender (8,17,32,38) disparities. One difference is that synchrony between input (effector concentration) and output (secretion response) patterns as assessed here is scale invariant.…”

Section: Discussionmentioning

confidence: 97%

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Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

Liu¹,

Pincus²,

Keenan³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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In the present study, we contrasted in vivo linkages within and between these two axes using methods without linearity assumptions. We examined 11 young (21-31 yr) and 8 older (62-74 yr) men who underwent frequent (every 2.5 min) blood sampling overnight for paired measurement of LH and testosterone and 35 adults (17 women and 18 men; 26 -77 yr old) who underwent adrenocorticotropic hormone (ACTH) and cortisol measurements every 10 min for 24 h. To mirror physiological interactions, hormone secretion was first deconvolved from serial concentrations with a waveform-independent biexponential elimination model. Feedforward synchrony, feedback synchrony, and the difference in feedforward-feedback synchrony were quantified by the cross-approximate entropy (X-ApEn) statistic. These were applied in a forward (LH concentration template, examining pattern recurrence in testosterone secretion), reverse (testosterone concentration template, examining pattern recurrence in LH secretion), and differential (forward minus reverse) manner, respectively. Analogous concentration-secretion X-ApEn estimates were calculated from ACTH-cortisol pairs. X-ApEn, a scale-and model-independent measure of pattern reproducibility, disclosed 1) greater testosterone-LH feedback coordination than LH-testosterone feedforward synchrony in healthy men and significant and symmetric erosion of both feedforward and feedback linkages with aging; 2) more synchronous ACTH concentration-dependent feedforward than feedback drive of cortisol secretion, independent of gender and age; and 3) enhanced detection of bidirectional physiological regulation by in vivo pairwise concentration-secretion compared with concentrationconcentration analyses. The linking of relevant biological input to output signals and vice versa should be useful in the dissection of the reciprocal control of neuroendocrine systems or even in the analysis of other nonendocrine networks.gonadal; adrenal; synchrony AGING IS MARKED BY A 30 -50% decline in systemic testosterone concentrations in healthy community-dwelling men, as recognized nearly 50 yr ago (11,46). Subsequent longitudinal (5,9,20) and population-based cross-sectional (2, 7, 19, 37) studies have corroborated relative androgen depletion in aging men. Other epidemiological data have correlated hypoandrogenemia with sarcopenia, osteopenia, reduced physical stamina, sexual dysfunction, impaired quality of life, and (possibly) depressive mood and cognitive impairment (46). Recent interventional studies suggest that reduced testosterone availability may be relevant to frailty in aging men (18,36). In parallel with therapeutic notions, mechanistic investigations are needed to determine why aging is associated with hypoandrogenemia. Few studies have appraised the effect of aging on nonlinear interactions, which are expected from time-delayed asymptotic dose-response connections among gonadotropin-releasing hormone (GnRH), LH, and testosterone. Recent developments of regulatory statistics and their validation in mathematical, laborat...

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Section: Discussionmentioning

confidence: 97%

“…In large population-based studies, late-day cortisol concentrations rise consistently with age, whereas single morning values are variable (1,3,4,13,17,38,39,51). Feedback analyses based on acute administration of synthetic and natural glucocorticoids suggest diminished inhibitory efficacy in older individuals, especially in women.…”

mentioning

confidence: 99%

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

Liu¹,

Pincus²,

Keenan³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Many studies have found an inverse relation between delta sleep and pulsatile cortisol release (see Vgontzas et al, 1999;Born et al, 1991 for a review). Normal aging is associated with a concurrent rise in secretory HPA activity and a reduction in delta sleep (Dodt et al, 1994;Feinberg et al, 1967;Gillin et al, 1981;Van Cauter et al, 1996). Aging is also associated with increased cortisol response and more decreases in delta sleep in response to mild laboratory stressors (Prinz et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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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“…Results from cross-sectional studies indicate that the basal cortisol level does not change with age [22,23] . Others report subtle increases in cortisol during normal aging [24][25][26] . In a longitudinal study, Lupien et al [23] identified a subgroup of individuals that exhibited elevated and increasing cortisol levels.…”

Section: Introductionmentioning

confidence: 99%

Increased Saliva Cortisol Awakening Response in Patients with Mild Cognitive Impairment

Lind¹,

Edman²,

Nordlund³

et al. 2007

Dement Geriatr Cogn Disord

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Background: It is unknown whether HPA-axis dysfunction is present in patients with mild cognitive impairment (MCI). The aim of the present study was to investigate whether cortisol levels are elevated among patients with MCI and/or whether the individuals have adequate feedback control of their HPA axis. Material and Methods: 27 patients with MCI and 15 healthy controls were included in the study. Saliva samplings were performed 5 times a day before intake of 0.5 mg dexamethasone, and 5 times a day after intake of dexamethasone, respectively. Results: Significantly higher cortisol levels were found 15 min after awakening among patients with MCI in comparison with the controls, both before and after dexamethasone administration (p < 0.05). Also, the ratio between cortisol at awakening time and 15 min after awakening was lower in the patient group after dexamethasone administration (p < 0.05). There were no significant differences in basal cortisol levels before or after dexamethasone between groups. Conclusion: The results indicate that there is an HPA-axis disturbance, with normal basal cortisol levels and increased awakening response among patients with MCI. The dissociation between basal values and the awakening response may be of pathophysiological importance for the cognitive impairment.

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Basal secretory activity of the hypothalamo–pituitary–adrenocortical axis is enhanced in healthy elderly. An assessment during undisturbed night-time sleep

Cited by 72 publications

References 30 publications

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Increased Saliva Cortisol Awakening Response in Patients with Mild Cognitive Impairment

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